4.2 Diseases of erythrocytes

But changes in erythrocyte shape, area, and volume may be caused by malaria, sickle cell disease, and other related erythrocytes diseases. Malaria parasites of clinical and laboratory importance include P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi in human and could be treated using orthodox and traditional medicine [35]. The gorilla, chimpanzee, orangutan, gibbon, and monkey also contract various species of malaria. Aotus trivirgatus (species of monkey) are experimental models for human P. vivax and P. falciparum. P. berghei discovered in Grammomys sudaster is a model of experiment for mammalian malaria. Mice and young rats could also be used as models for P. berghei which is very fatal, causing death in 1–3 weeks when less than 107 P. berghei was inoculated. P. relictum, P. gallinaceum, P. cathemerium, and P. lophurae are also used as models of experiment. P. durae and P. juxtanucleare caused 96% mortality in turkey [36] indicating that malaria could be a source of low erythrocyte count in all the species mentioned above. Consistent acridine orange staining of thin blood film for malaria parasites

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals DOI: http://dx.doi.org/10.5772/intechopen.85865

and rapid staining tests produce superior results in comparison to Giemsa method [37].

Sickle cell disease (SCD) is characterized by dense dehydrated red blood cells (DRBCs) that undergo polymerization and sickling due to sickle cell hemoglobin (Hbs) concentration. DRBCs in sickle cell disease patients caused priapism, renal dysfunction, skin ulcer, deletion of α-thalassemia, hyperbilirubinemia, and increased lactate dehydrogenase [38]. There is comorbidity of SCD and malaria among indigenes of Northwestern Nigeria with highest incidence of SS (51.8%), SC (28.4%), AS (16.2%), and SS + F (3.6%), respectively. Hemophilia, epistaxis, and splenomegaly, among others, are associated with SCD. Weight, packed cell volume, hemoglobin, total blood volume, red blood cell volume, and plasma volume are seriously affected in sickle cell patients that are not therapeutically managed causing the need for blood transfusion. Good prognosis is guaranteed by polypharmacy that involves the use of hematonic, anti-sickling, analgesic, antimalarial, and antiinflammatory drugs. Patients from Northwestern Nigeria can live up to 49 years [24]. Raphanus sativus, Arbutus unedo, Luffa acutangula, Lycopersicum esculentum, Cucumis melo, Brassica oleracea var. capitata, Allium porrum, Petroselinum sativum, Phoenix dactylifera, and Ficus carica can be used for management of blood and blood-related diseases including the diseases of erythrocytes [39, 40]. Efforts made toward antimalarial vaccine may be much near to fruition [35].

Autoimmune hemolytic anemia is associated with erythrocytes characterized by hemolysis and autoantibodies of anti-erythrocytes. Neurological sign is common in pernicious anemia. However normal morphology of erythrocytes and leucocytes is necessary for diagnosis of idiopathic thrombocytopenic purpura. But pernicious anemia is characterized by dyserythropoiesis and low vitamin B12 with antiintrinsic factor and anti-gastric mural cell antibodies being positive. Hence pernicious anemia is treated using vitamin B12 [41]. Complete blood count (CBC) identifies anemia, thrombocytopenia, leukopenia, polycythemia, thrombocytosis, and leukocytosis, but 10–20% of results are abnormal [42].

The life span of erythrocytes in human is 120 days; 20 μl of the erythrocytes are produced daily. But the circulating red blood cells vary among individuals of the same age and gender by over 10%. Mechanisms of anemia in solid tumors are by intrinsic or iatrogenic blood loss; iron or folic acid deficiency; autoimmune, traumatic, or drug-induced hemolysis; bone marrow factor caused by myelofibrosis; marrow necrosis; infection; inflammation; and cancer elsewhere in the body. Erythropoietin is important in the production of erythrocytes. Erythropoietin maybe impaired by tumor inflammatory cytokines [43]. Erythrocytes and hemoglobin promote tumor cell growth by increasing nucleotide-binding oligomerization domain-like receptors' expression and cause induction of IL-1b release, macrophage recruitment, and polarization. Therefore, hemorrhage could be used as a sign of therapeutic failure in cancer patients, because it promotes tumor cell growth and anticancer drug resistance [44]. Facilitation of breast cancer treatment by nanoscaled erythrocytes is via a combination of photodynamic, photothermal, and chemotherapy [45]. Erythrocytes can be lost in the blood lost from cancer surgery and anticancer drugs which affect fast-dividing normal cells and cancerous cells, indicating the drugs cannot differentiate good cells from bad cells [41].

Low calcium concentrations were reported in erythrocytes of patients with depressive disorders [46] indicating that erythrocytes could be used to assess therapeutic success of depressive illness and high calcium level could abate the disease. There was higher concentration of soluble catechol-O-methyltransferase (COMT) in erythrocytes of patients suffering from bulimia nervosa and binge eating disorder than anorexia nervosa [47] indicating that erythrocytes could be used for diagnosis of eating disorders. Favism, neonatal icterus, hereditary non-spherocytic hemolytic

animals. But reference value of hemoglobin concentration for swine (10–16 g/dl), sheep (8–16 g/dl), cow (15–18 g/dl), rabbit (10–15 g/dl), and guinea pig (11–15 g/dl), respectively, indicates that cow has the highest hemoglobin concentration, perhaps resulting from hemolysis. Toxicants, environmental factors, genetics, age, sex, breed, and management system could affect erythrocytes of farm animals [33]. An image-based error (3%) for counting of RBCs has been reported for Leopardus pardalis, Cebus apella, and Nasua nasua. However the RBC values for Canis

Blood smear from a monitor lizard (Varanus sp.). Slight distortion of the basophil (center) reveals the nucleus

), Equus caballus (6.10–11.0 106

) with the species showing RBC interval of

/μl) [34], respectively, show that erythrocyte volume varies from

), Cebus apella (3.49–5.48 106

But changes in erythrocyte shape, area, and volume may be caused by malaria, sickle cell disease, and other related erythrocytes diseases. Malaria parasites of clinical and laboratory importance include P. falciparum, P. vivax, P. malariae, P. ovale, and P. knowlesi in human and could be treated using orthodox and traditional medicine [35]. The gorilla, chimpanzee, orangutan, gibbon, and monkey also contract various species of malaria. Aotus trivirgatus (species of monkey) are experimental models for human P. vivax and P. falciparum. P. berghei discovered in Grammomys sudaster is a model of experiment for mammalian malaria. Mice and young rats could also be used as models for P. berghei which is very fatal, causing death in 1–3 weeks when less than 107 P. berghei was inoculated. P. relictum, P. gallinaceum, P. cathemerium, and P. lophurae are also used as models of experiment. P. durae and P. juxtanucleare caused 96% mortality in turkey [36] indicating that malaria could be a source of low erythrocyte count in all the species mentioned above. Consistent acridine orange staining of thin blood film for malaria parasites

/mm3

/mm3

), Leopardus

), and Nasua

/mm3

/mm3

/mm3

familiaris (5.50–8.50 106

species to species of animals.

4.2 Diseases of erythrocytes

pardalis (4.07–6.16 106

nasua (3.88–5.35 106

3.47–11.0 106

100

Figure 23.

Erythrocyte

and granules.

anemia, drug-induced hemolytic anemia, and hemolytic anemia due to infection are caused by increased destruction of erythrocytes with enzyme deficiencies. Quinine, chloroquine, sulfadiazine, phenytoin, isoniazid, chloramphenicol, ascorbic acid, and colchicine, among others, could be given in therapeutic doses to G-6-PDdeficient patients without non-spherocytic hemolytic anemia [48]. Hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis, and hereditary stomatocytosis are hemolytic anemias characterized by heterogeneity and treated by splenectomy which in turn causes complications of cardiovascular diseases, thromboembolic disorders, pulmonary hypertension, and penicillin-resistant pneumococci [49]. Human erythrocytes are subject to degree of genetic diversity. This variability results in anemia, cyanosis, polycythemia, non-hematologic alterations, sickling disorders, unstable hemoglobinopathies, or hemoglobinopathies associated with polycythemia, methemoglobinemia, and α- and β-thalassemias [48]. The cardiovascular effects of SCD and thalassemia are due to iron accumulation and hypoxia, respectively. The risk of thromboembolism should be assessed after splenectomy in the case of congenital chronic hemolytic anemia [50].

suggesting that hexavalent chromium has effect on gill protein. But RBCs of marine

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals

L. calcarifer than in M. cephalus, and total protein was also higher in L. calcarifer

than that of the female (23.41 � 1.67%), whereas hemoglobin (7.6 � 0.75 g/dl) is significantly higher in male than in the female Naja naja (3.25 � 0.74 g/dl), respectively [64]. The difference in the hematological parameters may be due to their nutrition, age, sex, and environment. Aqueous extract of Abrus precatorius seed

plant has anti-erythrocytic principle. Erythrocytes of albino rats increased from 7.2 � 0.14 � <sup>10</sup>12/L to 9.35 � 0.08 � <sup>10</sup>12/L. Packed cell volume, hemoglobin, and albumin were also increased significantly by aqueous ethanolic extract of Psidium guajava [17]. Escherichia coli caused hemolysis in Rattus norvegicus that was attenuated by aqueous root back extract of Byrsocarpus coccineus. E. coli was eliminated from the intestine and other organs by the extract [65]. Chinchilla chinchilla breed of the rabbit had increased erythrocytes, PCV, and hemoglobin as compared with other breeds [66]. Vernonia amygdalina and Carica papaya showed significant decrease in P. berghei parasites and increased RBCs and hematocrit in mice [67]. But Ficus thonningii aqueous extract has ameliorative activity against osmotic fragility induced by acetaminophen [68]. Various extracts of A. precatorius showed activity against parasites of erythrocytes such as Plasmodium, Leishmania, and Trypanosoma species with 1C50 of 12.1 � 4.59 μg/ml [69]. Ceftriaxone caused increased packed cell volume, hypobilirubinemia, and increased bicarbonate ions in turkeys [15]. However human equivalent dose (HED) formula could be modified for determination of hematological and biochemical parameters [70]. About 8% of body weight correlates very well with plasma cell volume and hematocrit [2]. But many varieties of body surface area formulas could also yield different values of erythrocytes. Wang et al.'s formula may provide moderate doses of anticancer drugs against blood cell cancers [71]. Aqueous leaf extract of A. precatorius cleared signif-

from 38.00 � 1.22 to 32.00 � 1.41%, and hemoglobin from 12.65 � 0.9 to 10.68 � 0.47 g/dl, respectively. Distemper-hepatitis-leptospirosis-parvovirusparainfluenza (DHLPPi) vaccine decreased in dog, hematological parameters at dose level of >2 mg/kg body weight. The same dose of the extract and DHLPPi caused hypoalbuminemia and hypoglobulinemia and decreased total albuminglobulin ratio. Hence the two could be used in prevention of chronic viral infection in dogs [13], signifying that erythrocytes have relationship with plasma proteins and may be used to determine immune status of animals. Methanol and ethanol seed extract of Abrus precatorius decreased erythrocytes from 9.60 � 1.02 to

=μl), respectively. But hemoglobin and hematocrit were higher in

=μl), are higher than that

=μl, packed cell volume

, P. berghei appeared in

Number of total erythrocytes (3)

<sup>100</sup> (4)

=μl) and herbivorous Chanos chanos

/μl) are higher than that of the

=μl, respectively [14], indicating that the

/μl). PCV of the male (30.11 � 1.93%) is higher

teleost carnivorous fish, Lates calcarifer (2.96 � 0.25 � <sup>10</sup><sup>6</sup>

decreased erythrocytes from 6.33 � 0.2 to 5.33 � 0.24 � <sup>10</sup><sup>6</sup>

<sup>=</sup>μ<sup>l</sup> and 6.37 � 0.60 � <sup>10</sup><sup>6</sup>

icant percent of Plasmodium berghei in 14 days. However 10<sup>7</sup>

percent of parasitized erythrocytes is calculated as follows:

erythrocytes of mice within 24 hr after intraperitoneal inoculation [62]. Hence the

Number of parasites per microliter ð Þ μl of blood

<sup>¼</sup> WBC � parasites counted against 100 WBC

The percentage parasitized <sup>¼</sup> Number of infected erythrocytes x 100

of omnivorous Mugil cephalus (2.52 � 0.21 � <sup>10</sup><sup>6</sup>

DOI: http://dx.doi.org/10.5772/intechopen.85865

[22]. RBCs of male Naja naja (0.58 � 0.04 � <sup>10</sup><sup>6</sup>

female Naja naja (0.50 � 0.04 � 106

(2.0 � 0.51� <sup>10</sup><sup>6</sup>

7.13 � 0.34 � <sup>10</sup><sup>6</sup>

103

Autoimmune hemolytic anemia (AIHA) is potentially severe, characterized by destruction of RBCs and immunoglobulin G (IgG) anti-RBC [51]. Hence, RBC membrane could be used to diagnose autism spectrum disorders using biophotonics [52]. Therefore, relative deformability difference between tumor cells and blood cells as indicated by the length of time [53] may be used to diagnose and determine prognosis of some erythrocyte-related diseases and therapeutic interventions. Small intestinal resection and anastomosis by 70% decreased RBC from 6.23 to 5.1% preadministration of glutamine. However, RBC decreased from 5.8 to 4.5% on the 12th day of experimentation. Honey, ascorbic acid, and glutamine caused decreased erythrocytes in intestinal resection and anastomosis in dogs [54]. Canine parvoviral enteritis causes anemia with highest incidence in Nigerian local dog occurring in January of every year and prevalence of 5.7% for the past 7 years [55]. Erythrocyte sedimentation is the speed with which erythrocyte levels fall in the blood of normal animals over a period of time. Hence diseased animals have high ESR, whereas healthy animals have low ESR [56] signifying that erythrocyte diseases can be diagnosed using ESR.

#### 4.3 Effects of toxic agents on erythrocytes

Potassium permanganate (16 mg/kg) decreased hematocrit from 41.00 2.08 to 39.29 2.43% with attendant hypochloremia [16]. Salinity increased hematocrit and decreased hemoglobin of juvenile Nile tilapia (Oreochromis niloticus) [57]. Hypertonic saline (20%) could decrease hematocrit, total protein, and albumin [58] invariably decreasing erythrocytes and perhaps increasing hemoglobin. Toxic agents such as plants, drugs, venoms, antivenoms, chemicals, uroliths, and some food additives could damage erythrocytes and consequently cause anemia [59, 61]. Halofantrine, sulfadimidine, chloramphenicol, and other many drugs and chemicals are toxic to erythrocytes [10, 15, 62]. But erythrocytes decreased in Baladi goat during the last 3 weeks of parturition and remained low 2 weeks after parturition [63] perhaps due to significant blood loss.

#### 4.4 Effects of therapeutic agents on erythrocytes

Hexavalent chromium increased erythrocytes from 1.3 0.03 to 1.05 0.05 10<sup>6</sup> =μl after 24 h in Labeo rohita (Indian Major Carp), whereas hemoglobin was increased from 8.1 6.7 to 6.80 0.96 g/dl in the same species of animal. Also total protein of gill was decreased from 192.79 4:08 to 171.78 3.64 g/dl [19]

suggesting that hexavalent chromium has effect on gill protein. But RBCs of marine teleost carnivorous fish, Lates calcarifer (2.96 � 0.25 � <sup>10</sup><sup>6</sup> =μl), are higher than that of omnivorous Mugil cephalus (2.52 � 0.21 � <sup>10</sup><sup>6</sup> =μl) and herbivorous Chanos chanos (2.0 � 0.51� <sup>10</sup><sup>6</sup> =μl), respectively. But hemoglobin and hematocrit were higher in L. calcarifer than in M. cephalus, and total protein was also higher in L. calcarifer [22]. RBCs of male Naja naja (0.58 � 0.04 � <sup>10</sup><sup>6</sup> /μl) are higher than that of the female Naja naja (0.50 � 0.04 � 106 /μl). PCV of the male (30.11 � 1.93%) is higher than that of the female (23.41 � 1.67%), whereas hemoglobin (7.6 � 0.75 g/dl) is significantly higher in male than in the female Naja naja (3.25 � 0.74 g/dl), respectively [64]. The difference in the hematological parameters may be due to their nutrition, age, sex, and environment. Aqueous extract of Abrus precatorius seed decreased erythrocytes from 6.33 � 0.2 to 5.33 � 0.24 � <sup>10</sup><sup>6</sup> =μl, packed cell volume from 38.00 � 1.22 to 32.00 � 1.41%, and hemoglobin from 12.65 � 0.9 to 10.68 � 0.47 g/dl, respectively. Distemper-hepatitis-leptospirosis-parvovirusparainfluenza (DHLPPi) vaccine decreased in dog, hematological parameters at dose level of >2 mg/kg body weight. The same dose of the extract and DHLPPi caused hypoalbuminemia and hypoglobulinemia and decreased total albuminglobulin ratio. Hence the two could be used in prevention of chronic viral infection in dogs [13], signifying that erythrocytes have relationship with plasma proteins and may be used to determine immune status of animals. Methanol and ethanol seed extract of Abrus precatorius decreased erythrocytes from 9.60 � 1.02 to 7.13 � 0.34 � <sup>10</sup><sup>6</sup> <sup>=</sup>μ<sup>l</sup> and 6.37 � 0.60 � <sup>10</sup><sup>6</sup> =μl, respectively [14], indicating that the plant has anti-erythrocytic principle. Erythrocytes of albino rats increased from 7.2 � 0.14 � <sup>10</sup>12/L to 9.35 � 0.08 � <sup>10</sup>12/L. Packed cell volume, hemoglobin, and albumin were also increased significantly by aqueous ethanolic extract of Psidium guajava [17]. Escherichia coli caused hemolysis in Rattus norvegicus that was attenuated by aqueous root back extract of Byrsocarpus coccineus. E. coli was eliminated from the intestine and other organs by the extract [65]. Chinchilla chinchilla breed of the rabbit had increased erythrocytes, PCV, and hemoglobin as compared with other breeds [66]. Vernonia amygdalina and Carica papaya showed significant decrease in P. berghei parasites and increased RBCs and hematocrit in mice [67].

But Ficus thonningii aqueous extract has ameliorative activity against osmotic fragility induced by acetaminophen [68]. Various extracts of A. precatorius showed activity against parasites of erythrocytes such as Plasmodium, Leishmania, and Trypanosoma species with 1C50 of 12.1 � 4.59 μg/ml [69]. Ceftriaxone caused increased packed cell volume, hypobilirubinemia, and increased bicarbonate ions in turkeys [15]. However human equivalent dose (HED) formula could be modified for determination of hematological and biochemical parameters [70]. About 8% of body weight correlates very well with plasma cell volume and hematocrit [2]. But many varieties of body surface area formulas could also yield different values of erythrocytes. Wang et al.'s formula may provide moderate doses of anticancer drugs against blood cell cancers [71]. Aqueous leaf extract of A. precatorius cleared significant percent of Plasmodium berghei in 14 days. However 10<sup>7</sup> , P. berghei appeared in erythrocytes of mice within 24 hr after intraperitoneal inoculation [62]. Hence the percent of parasitized erythrocytes is calculated as follows:

$$\text{The percentage passed} = \frac{\text{Number of infected everythings x 100}}{\text{Number of total ethylroscopetes}} \quad \text{(3)}$$

Number of parasites per microliter ð Þ μl of blood

$$=\frac{\text{WBC} \times \text{parasites counted against 100 WBC}}{100} \tag{4}$$

anemia, drug-induced hemolytic anemia, and hemolytic anemia due to infection are caused by increased destruction of erythrocytes with enzyme deficiencies. Quinine, chloroquine, sulfadiazine, phenytoin, isoniazid, chloramphenicol, ascorbic acid, and colchicine, among others, could be given in therapeutic doses to G-6-PDdeficient patients without non-spherocytic hemolytic anemia [48]. Hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis, and hereditary stomatocytosis are hemolytic anemias characterized by heterogeneity and treated by splenectomy which in turn causes complications of cardiovascular diseases, thromboembolic disorders, pulmonary hypertension, and penicillin-resistant pneumococci [49]. Human erythrocytes are subject to degree of genetic diversity. This variability results in anemia, cyanosis, polycythemia, non-hematologic alterations, sickling disorders, unstable hemoglobinopathies, or hemoglobinopathies associated with polycythemia, methemoglobinemia, and α- and β-thalassemias [48]. The cardiovascular effects of SCD and thalassemia are due to iron accumulation and hypoxia, respectively. The risk of thromboembolism should be assessed after sple-

Autoimmune hemolytic anemia (AIHA) is potentially severe, characterized by destruction of RBCs and immunoglobulin G (IgG) anti-RBC [51]. Hence, RBC membrane could be used to diagnose autism spectrum disorders using biophotonics [52]. Therefore, relative deformability difference between tumor cells and blood cells as indicated by the length of time [53] may be used to diagnose and determine prognosis of some erythrocyte-related diseases and therapeutic interventions. Small intestinal resection and anastomosis by 70% decreased RBC from 6.23 to 5.1% preadministration of glutamine. However, RBC decreased from 5.8 to 4.5% on the 12th day of experimentation. Honey, ascorbic acid, and glutamine caused decreased erythrocytes in intestinal resection and anastomosis in dogs [54]. Canine parvoviral enteritis causes anemia with highest incidence in Nigerian local dog occurring in January of every year and prevalence of 5.7% for the past 7 years [55]. Erythrocyte sedimentation is the speed with which erythrocyte levels fall in the blood of normal animals over a period of time. Hence diseased animals have high ESR, whereas healthy animals have low ESR [56] signifying that erythrocyte diseases can be

Potassium permanganate (16 mg/kg) decreased hematocrit from 41.00 2.08 to 39.29 2.43% with attendant hypochloremia [16]. Salinity increased hematocrit and decreased hemoglobin of juvenile Nile tilapia (Oreochromis niloticus) [57]. Hypertonic saline (20%) could decrease hematocrit, total protein, and albumin [58] invariably decreasing erythrocytes and perhaps increasing hemoglobin. Toxic agents such as plants, drugs, venoms, antivenoms, chemicals, uroliths, and some food additives could damage erythrocytes and consequently cause anemia [59, 61]. Halofantrine, sulfadimidine, chloramphenicol, and other many drugs and chemicals are toxic to erythrocytes [10, 15, 62]. But erythrocytes decreased in Baladi goat during the last 3 weeks of parturition and remained low 2 weeks after parturition

Hexavalent chromium increased erythrocytes from 1.3 0.03 to 1.05 0.05 10<sup>6</sup> =μl after 24 h in Labeo rohita (Indian Major Carp), whereas hemoglobin was increased from 8.1 6.7 to 6.80 0.96 g/dl in the same species of animal. Also total

protein of gill was decreased from 192.79 4:08 to 171.78 3.64 g/dl [19]

nectomy in the case of congenital chronic hemolytic anemia [50].

diagnosed using ESR.

Erythrocyte

102

4.3 Effects of toxic agents on erythrocytes

[63] perhaps due to significant blood loss.

4.4 Effects of therapeutic agents on erythrocytes

Erythrocytes infected with 10<sup>7</sup> P. berghei decreased in 7 days by 19%, after inoculation. But aqueous extract of A. precatorius leaf and halofantrine caused 9.8 and 12.7% decrease in parasitemia, respectively. However mice-fed grower's marsh had erythrocyte increase of 6.7% in 7 days [62]. The administration of aqueous leaf extract of A. precatorius at 10 mg/kg i.p. caused increased hematocrit from 33.0 � 4.1 to 40.5 � 3.1% as compared to 50 mg/kg oral dose that caused 40.3 � 3.6%, respectively [72]. Gender, age, cholesterol, triglycerides, apoliprotein, and albumin affect hematological parameters [73]. Woman's blood has more fluid with 20% fewer erythrocytes than man's blood. Hence there is less supply of oxygen to body tissues in woman, and therefore she gets tired easily and is more prone to fainting [74]. But hot water increases blood supply to the muscle; hence water is contraindicated in acute bleeding [75].

#### 4.5 Relationship between body weight, body surface area, erythrocytes, and area under curve

Formulas have been derived from the existing formulas that could be used for calculation of body weight, blood volume, erythrocyte volume, and PCV. The derived formulas are:

$$\text{Total blood volume } (\text{TBV}) = 0.08 \text{BW} \tag{5}$$

Dose Dð Þ¼ AUC � ½ � CrCl þ 25 (16)

2  <sup>¼</sup> <sup>14616</sup>:<sup>8</sup> PCL�<sup>25</sup>

BW ¼ Km � BSA (19)

� BW � <sup>10</sup>�<sup>4</sup> (20)

� Km � BSA � <sup>10</sup>�<sup>4</sup> (21)

<sup>50</sup> � BW � <sup>10</sup>�<sup>4</sup> (23)

BSA (18)

(17)

where D ¼ dose of either therapeutic agent or toxicant that has an effect on erythrocytes, blood volume, and plasma volume and AUC = area under curve.

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals

Creatinine half � life Crt <sup>1</sup>

of relevant parameters [77]:

where PCL = plasma clearance.

DOI: http://dx.doi.org/10.5772/intechopen.85865

where BSA = body surface area [78].

animals, and 10�4= safety factor [79]. Substitute BW of Eq. (19) in Eq. (20):

However, pharmacokinetic data are more useful in relation to disease of pathological findings instead of focusing on the mean data in relation to risk assessment [76]. Baseline variable is important to consider when using AUC for determination

Metabolism constant Km ð Þ¼ BW

However toxic agent could cause lethality by destroying erythrocytes. The amount of a toxicant that causes death in 50% of test animals is called median lethal dose (LD50). The formula is used for determination of both median lethal and

3

3

where LD50 ¼ median lethal dose of toxic agent that has an effect on erythrocytes of 50% of test animals, ED50 ¼ dose that has therapeutic effect on 50% of test

Equations (18)–(21) are relevant in the study using experimental animals. However, there are various human body surface area formulas that vary from race to race and could be used in calculation of body surface area [80]. But the unique body surface area formula for human and dog may be relevant [81], and it is given below:

BSA <sup>¼</sup> BW<sup>0</sup>:<sup>528</sup> � H0:<sup>528</sup> � K where K ð Þ <sup>¼</sup> constant <sup>¼</sup> <sup>0</sup>:<sup>14</sup> (22)

The height of dog must be multiplied by 2, and it is always in meter. More so Treeing Walker Coonhound (65 kg), female Komondor (59 kg), Greater Swiss mountain dog (59 kg), French Mastiff (50 kg), and long-haired St. Bernard (55 kg) have the same body surface area of humans weighing 51.3, 59, 46.7, 44, and 44.8 kg, respectively [81], and the two may have the same erythrocytes and other hematological values. Also, malignant lymphoma (cancer of the white blood cells) and other blood-related cancers can be treated using some other established BSA formulas [80]. But, scorpion sting can cause bleeding, leading to anemia and death. Hence the formula for determination of median lethal dose (LD50) of scorpion

median effective dose of snake venom and antivenom, respectively:

<sup>∴</sup>LD50 <sup>¼</sup> ED50

Hence LD50 <sup>¼</sup> ED50

venom in experimental animals is given below [82]:

105

LD50 <sup>¼</sup> ED<sup>1</sup>=<sup>3</sup>

$$\text{TBV} = \text{Plasma volume } (\text{PV}) \times \frac{100}{100 - \text{Haematorit}} \tag{6}$$

$$\text{Haemtocrit} \left( \text{RCV} \right) = \text{TBV} - \text{PV} \tag{7}$$

Equate Eqs. (5) and (6):

$$\text{TBV} = 0.08 \text{ BW} = \text{PV} \times \frac{100}{100 - Haematorit} \tag{8}$$

$$10.08 \text{BW} = \text{PV} \times \frac{100}{100 - \text{Haematorit}} \tag{9}$$

$$\text{BW} = \text{PV} \times \frac{100}{\frac{100 - \text{Haematorit}}{0.08}} \tag{10}$$

$$\text{BW} = \text{PV} \times \frac{100}{100 - Haematorit} \times \frac{1}{0.08} \tag{11}$$

But 0.08 = 8% [2].

$$\text{But creatinine clearance } (CrCl) = \frac{\text{K} \times (140 - \text{age}) \times \text{BW}}{\text{D} \times \text{Srr} \times 72} \tag{12}$$

Substitute BW of Eq. (11) in Eq. (12):

$$\text{Hence } GrCl = \frac{K \times (140 - age) \times PV \times \frac{100}{100 - Haematorit} \times \frac{1}{0.08}}{\text{D x Scr x } 72} \tag{13}$$

$$\text{But serum creatinine} \left(\text{Scr}\right) = \frac{Pcr}{1440} \times 1000 \text{ ml} \tag{14}$$

Ucr ¼ urine creatinine; Pcr ¼ plasma creatinine

$$\mathbf{D} \left( \text{Depuration} \right) = \frac{\mathbf{Ucr}}{\mathbf{Pcr}} \tag{15}$$

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals DOI: http://dx.doi.org/10.5772/intechopen.85865

$$\text{Dose}\,(\text{D}) = \text{AUC} \times [\text{CrCl} + \text{25}] \tag{16}$$

where D ¼ dose of either therapeutic agent or toxicant that has an effect on erythrocytes, blood volume, and plasma volume and AUC = area under curve.

However, pharmacokinetic data are more useful in relation to disease of pathological findings instead of focusing on the mean data in relation to risk assessment [76]. Baseline variable is important to consider when using AUC for determination of relevant parameters [77]:

$$\text{Creatinine half} - \text{life} \left( \text{Crt} \, \frac{1}{2} \right) = \frac{14616.8}{P\_{\text{CL}-25}} \tag{17}$$

where PCL = plasma clearance.

Erythrocytes infected with 10<sup>7</sup> P. berghei decreased in 7 days by 19%, after inoculation. But aqueous extract of A. precatorius leaf and halofantrine caused 9.8 and 12.7% decrease in parasitemia, respectively. However mice-fed grower's marsh had erythrocyte increase of 6.7% in 7 days [62]. The administration of aqueous leaf

40.3 � 3.6%, respectively [72]. Gender, age, cholesterol, triglycerides, apoliprotein, and albumin affect hematological parameters [73]. Woman's blood has more fluid with 20% fewer erythrocytes than man's blood. Hence there is less supply of oxygen to body tissues in woman, and therefore she gets tired easily and is more prone to fainting [74]. But hot water increases blood supply to the muscle; hence water is

4.5 Relationship between body weight, body surface area, erythrocytes, and

TBV <sup>¼</sup> Plasma volume PV ð Þ� <sup>100</sup>

TBV ¼ 0:08 BW ¼ PV �

0:08BW ¼ PV �

BW ¼ PV �

Substitute BW of Eq. (11) in Eq. (12):

BW ¼ PV �

Hence CrCl <sup>¼</sup> <sup>K</sup> � ð Þ� <sup>140</sup> � age PV � <sup>100</sup>

But serum creatinine Scr ð Þ¼ Pcr

Formulas have been derived from the existing formulas that could be used for calculation of body weight, blood volume, erythrocyte volume, and PCV. The

Total blood volume TBV ð Þ¼ 0:08BW (5)

Haemtocrit RCV ð Þ¼ TBV � PV (7)

100

� 1

<sup>100</sup>�Haematocrit � <sup>1</sup>

1440

D x Scr x 72 (13)

100

100 100�Haematocrit 0:08

100 100 � Haematocrit

But creatinine clearance ð Þ¼ CrCl <sup>K</sup> � ð Þ� <sup>140</sup> � age BW

Ucr ¼ urine creatinine; Pcr ¼ plasma creatinine D Depuration ð Þ¼ Ucr

<sup>100</sup> � Haematocrit (6)

<sup>100</sup> � Haematocrit (8)

<sup>0</sup>:<sup>08</sup> (11)

<sup>D</sup> � Scr � <sup>72</sup> (12)

0:08

Pcr (15)

� 1000 ml (14)

(10)

<sup>100</sup> � Haematocrit (9)

extract of A. precatorius at 10 mg/kg i.p. caused increased hematocrit from 33.0 � 4.1 to 40.5 � 3.1% as compared to 50 mg/kg oral dose that caused

contraindicated in acute bleeding [75].

area under curve

Erythrocyte

derived formulas are:

Equate Eqs. (5) and (6):

But 0.08 = 8% [2].

104

$$\text{Metabolic constant (Km)} = \frac{\text{BW}}{\text{BSA}}\tag{18}$$

$$\mathbf{BW} = \mathbf{Km} \times \mathbf{BSA} \tag{19}$$

where BSA = body surface area [78].

However toxic agent could cause lethality by destroying erythrocytes. The amount of a toxicant that causes death in 50% of test animals is called median lethal dose (LD50). The formula is used for determination of both median lethal and median effective dose of snake venom and antivenom, respectively:

$$\text{LiLD}\_{50} = \frac{\text{ED}\_{50}}{\text{3}} \times \text{BW} \times \text{10}^{-4} \tag{20}$$

where LD50 ¼ median lethal dose of toxic agent that has an effect on erythrocytes of 50% of test animals, ED50 ¼ dose that has therapeutic effect on 50% of test animals, and 10�4= safety factor [79].

Substitute BW of Eq. (19) in Eq. (20):

$$\text{Hence } \text{LD}\_{50} = \frac{\text{ED}\_{50}}{3} \times \text{K}m \times BSA \times 10^{-4} \tag{21}$$

Equations (18)–(21) are relevant in the study using experimental animals. However, there are various human body surface area formulas that vary from race to race and could be used in calculation of body surface area [80]. But the unique body surface area formula for human and dog may be relevant [81], and it is given below:

$$\text{BSA} = \text{BW}^{0.528} \times \text{H}^{0.528} \times \text{K} \, (\text{where } \text{K} = \text{constant} = 0.14) \tag{22}$$

The height of dog must be multiplied by 2, and it is always in meter. More so Treeing Walker Coonhound (65 kg), female Komondor (59 kg), Greater Swiss mountain dog (59 kg), French Mastiff (50 kg), and long-haired St. Bernard (55 kg) have the same body surface area of humans weighing 51.3, 59, 46.7, 44, and 44.8 kg, respectively [81], and the two may have the same erythrocytes and other hematological values. Also, malignant lymphoma (cancer of the white blood cells) and other blood-related cancers can be treated using some other established BSA formulas [80]. But, scorpion sting can cause bleeding, leading to anemia and death. Hence the formula for determination of median lethal dose (LD50) of scorpion venom in experimental animals is given below [82]:

$$\text{LD}\_{50} = \text{ED}\_{50}^{\dagger \circ} \times \text{BW} \times \text{10}^{-4} \tag{23}$$

#### 4.6 Transport of oxygen by erythrocytes

Erythrocytes in contact with alveoli receive oxygen which is combined with hemoglobin (oxyhemoglobin) and transported to various parts of the body. After the delivery of oxygen, the erythrocytes return CO2 combined with hemoglobin (deoxyhemoglobin) which is bluish in color to the alveoli for expiration. Hence the following reaction occurs in the erythrocytes:

$$\text{H}\_2\text{O} + \text{CO}\_2 \overset{\text{\textdegree}}{\text{H}}\_2\text{CO}\_3 \overset{\text{\textdegree}}{\text{H}}\_2\text{H}^+ + \text{HCO}\_3^{\text{\textdegree}} \overset{\text{\textdegree}}{\text{H}}\_2\text{O} + \text{CO}\_2 \tag{24}$$

The erythrocytes are elliptical, larger, and not bending, with decreased blood cell count. But nonnucleated erythrocytes exhibit nonalignment. Hence erythrocytes of bird are flattened, lenticular, spherical, and folded when deformed [99]. Hemoglobin concentration of nonmammalian erythrocytes is 15–20% higher than that of mammalian species, with increased RBC density, and the nucleus contains 20% of cytoplasmic volume [100, 101] with RBC rigidity [102]. However, RBCs of reptiles are least decreased than that of mammal, the membrane having shear elastic modulus [103]. But fish might have the largest RBC volumes. The cells are elliptical and bulge in the region of their nucleus. Fish hematocrit drops with water temperature and can change due to the environmental temperature [104]. Aggregation capacity of equine erythrocyte is higher than that of dog and sheep, but could not be measured. There is species variation in erythrocyte elongation not linked with the aggregation property. Also deformability of erythrocytes is species-specific [105]. Tannic acid increases or decreases agglutinability of erythrocytes in the presence of immune serum [106]. Attachment of endotoxins, e.g., lipopolysaccharide antigen, to erythrocytes was strongly prevented by mammalian and avian sera followed by that of reptilian (moderate) and amphibian (minimal) [107]. But temperature has no effect on flexibility of horse, cattle, sheep, goat, and some human erythrocytes indicating that blood viscosity varies with temperature [108]. Diameter, circumference, and surface area are higher in erythrocytes of dog followed by horse, cattle,

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals

Ion transport pathways of the erythrocytes are Na<sup>þ</sup> � K<sup>þ</sup> � Cl�, Na<sup>þ</sup> � Cl�, and Na<sup>þ</sup> � K<sup>þ</sup> through AQPI water and SKI� Gardos channels using ATPase [110]. Major metabolic pathway in erythrocytes is as follows: glucose is converted to glucose-6-phosphate to fructose-6-phosphate to pyruvate to lactate [111]. Reduced or defective erythrocytes result in nonregenerative anemia, and increased cell loss results in regenerative anemia, respectively [112]. Cellular shape and flexibility of erythrocytes are dependent on metabolic process which is via enzymes that are associated with erythrocyte defects [113]. Spherocytes have less diameter and thickness greater than normal resulting from hereditary spherocytosis seen in the peripheral blood smear of neonates with ABO incompatibility [114], releasing lipids, causing adenosine triphosphate depletion, and exposing the cells to shear stress [115]. Methods used for measurements of erythrocytes deformability are filtration microfluidic filtration and laser diffractometry. Deformation of RBCs has to do with the geometry, hemoglobin concentration, rheological properties, osmotic concentration, calcium, nitric oxide, temperature, membrane protein and lipid alteration, erythrocyte ATP, and erythrocyte aging. But measurements of individual cells are by micropipette aspiration, atomic force microscopy, optical tweezers, and

quantitative phase imaging. Also, there is correlation between erythrocyte deformability and diabetic microangiopathy [116]. Eosin-5-maleimide (EMA) binding test and osmotic fragility test differentiate hereditary spherocytosis from hereditary stomatocytosis [117]. Morphological changes in the sickle cell hemoglobin caused by deoxygenation of RBCs could lead to high metabolic activity and shortened life span of erythrocytes in sickle cell disease patients [118] invariably leading to anemia. The mechanism extent, levels, and complement involvement differ considerably in autoimmune hemolytic anemia [119]. Erythrocyte membrane disorders including hereditary spherocytosis and elliptocytosis could be diagnosed by red blood cell cytology, ektacytometry, flow cytometry, electrophoresis, and

mutational analysis of cell membrane proteins [120].

107

sheep, and goat in that order [109].

4.8 Metabolic pathway of erythrocytes

DOI: http://dx.doi.org/10.5772/intechopen.85865

The presence of COOH and C=O in piroxicam and other chemically related compounds [83] may interfere with chemistry of erythrocytes causing hemolysis and anemia. Also degradation products of some polymers, poly(lactic-co-glycolic acid), polyethylene glycol, polycaprolactone, and poly(propylene glycol) are converted to lactic acid and glycolic acid which are in turn converted to carbon dioxide and water [84] indicating that some polymers could also affect erythrocytes. Polycythemia could be confirmed by hyperpnea. Meat from an animal poisoned with potassium permanganate could react with 0.2% ethanolic benzidine changing the color of meat to dark green in 1–2 s [85], and potassium permanganate causes hyperpnea. Lowest oxygen saturation could be improved by zolpidem [86]. Erythrocytes of cow, dog, goat, horse, pig, rabbit, rat, and sheep composed greatly of cholesterol and cholesteryl esters, triglycerides, and free fatty acids are present in trace quantity. They may not be true constituents of erythrocytes, but rather contaminants from plasma lipoproteins or leucocytes. Cholesterol is 30% of cell lipid and has molar ratio with phospholipid [87] and may affect oxygen capacity of erythrocytes. Hence cow, sheep, horse, rabbit, and chicken erythrocytes are susceptible to Vibrio vulnificus hemolysin with varying degrees of susceptibility [88] and may cause anemia and less oxygen transport. Human coagulation factor 1X (F-1X) activated by human RBCs causes coagulation activated by enzyme in the RBC membrane. However, in dog, cattle, rabbit, and sheep, coagulation did not occur except in pig when procoagulant was used. Hence coagulation activation of enzyme may be present in these species of animals [89].

Lysis of erythrocytes by toxins of cobra could cause anemia and splitting of phospholipids in equal capacity in rabbit, dog, human, and guinea pig, but not in camel and sheep erythrocytes. Phosphatide acylhydrolase is responsible for splitting of the erythrocytes. The action is via lytic factor which is hemolytic. The phospholipase readily hydrolyzes phospholipids of erythrocytes. Vipera palestinae could not lyse erythrocytes and hydrolyze phospholipids [90]. Plasma viscosity depends on plasma protein concentration [91], with cattle having 1.72 mpa s and rabbit (1.3 mpa s) with horse, dog, cat, mouse, rat, pig, and sheep having 1.3–1.7 mpa s. Man has a value lower than this range [92]. Deformability of RBCs is dependent on size and shape [93] with pig, hamster, rat, mouse, and rabbit having more deformable RBCs than sheep, horse, elephant, and dog. The deformity is characterized by RBC elongation and aggregation [94]. All these could affect oxygen transport. Non-irreversible sickle cells adhere more at normal oxygen tension, and more than 1% of the cells remained adhered to the monolayer at forces higher than physiologic shear stresses [95].

#### 4.7 Morphologic differences in erythrocytes of animals

Llama, dromedary, and camel have low hematocrit value and low RBC aggregation [96]. Such RBCs may be small and elliptical in shape [97]. Nonmammalian RBCs have nucleus and microtubular bundle connected to a marginal band [98].

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals DOI: http://dx.doi.org/10.5772/intechopen.85865

The erythrocytes are elliptical, larger, and not bending, with decreased blood cell count. But nonnucleated erythrocytes exhibit nonalignment. Hence erythrocytes of bird are flattened, lenticular, spherical, and folded when deformed [99]. Hemoglobin concentration of nonmammalian erythrocytes is 15–20% higher than that of mammalian species, with increased RBC density, and the nucleus contains 20% of cytoplasmic volume [100, 101] with RBC rigidity [102]. However, RBCs of reptiles are least decreased than that of mammal, the membrane having shear elastic modulus [103]. But fish might have the largest RBC volumes. The cells are elliptical and bulge in the region of their nucleus. Fish hematocrit drops with water temperature and can change due to the environmental temperature [104]. Aggregation capacity of equine erythrocyte is higher than that of dog and sheep, but could not be measured. There is species variation in erythrocyte elongation not linked with the aggregation property. Also deformability of erythrocytes is species-specific [105]. Tannic acid increases or decreases agglutinability of erythrocytes in the presence of immune serum [106]. Attachment of endotoxins, e.g., lipopolysaccharide antigen, to erythrocytes was strongly prevented by mammalian and avian sera followed by that of reptilian (moderate) and amphibian (minimal) [107]. But temperature has no effect on flexibility of horse, cattle, sheep, goat, and some human erythrocytes indicating that blood viscosity varies with temperature [108]. Diameter, circumference, and surface area are higher in erythrocytes of dog followed by horse, cattle, sheep, and goat in that order [109].

#### 4.8 Metabolic pathway of erythrocytes

Ion transport pathways of the erythrocytes are Na<sup>þ</sup> � K<sup>þ</sup> � Cl�, Na<sup>þ</sup> � Cl�, and Na<sup>þ</sup> � K<sup>þ</sup> through AQPI water and SKI� Gardos channels using ATPase [110]. Major metabolic pathway in erythrocytes is as follows: glucose is converted to glucose-6-phosphate to fructose-6-phosphate to pyruvate to lactate [111]. Reduced or defective erythrocytes result in nonregenerative anemia, and increased cell loss results in regenerative anemia, respectively [112]. Cellular shape and flexibility of erythrocytes are dependent on metabolic process which is via enzymes that are associated with erythrocyte defects [113]. Spherocytes have less diameter and thickness greater than normal resulting from hereditary spherocytosis seen in the peripheral blood smear of neonates with ABO incompatibility [114], releasing lipids, causing adenosine triphosphate depletion, and exposing the cells to shear stress [115]. Methods used for measurements of erythrocytes deformability are filtration microfluidic filtration and laser diffractometry. Deformation of RBCs has to do with the geometry, hemoglobin concentration, rheological properties, osmotic concentration, calcium, nitric oxide, temperature, membrane protein and lipid alteration, erythrocyte ATP, and erythrocyte aging. But measurements of individual cells are by micropipette aspiration, atomic force microscopy, optical tweezers, and quantitative phase imaging. Also, there is correlation between erythrocyte deformability and diabetic microangiopathy [116]. Eosin-5-maleimide (EMA) binding test and osmotic fragility test differentiate hereditary spherocytosis from hereditary stomatocytosis [117]. Morphological changes in the sickle cell hemoglobin caused by deoxygenation of RBCs could lead to high metabolic activity and shortened life span of erythrocytes in sickle cell disease patients [118] invariably leading to anemia. The mechanism extent, levels, and complement involvement differ considerably in autoimmune hemolytic anemia [119]. Erythrocyte membrane disorders including hereditary spherocytosis and elliptocytosis could be diagnosed by red blood cell cytology, ektacytometry, flow cytometry, electrophoresis, and mutational analysis of cell membrane proteins [120].

4.6 Transport of oxygen by erythrocytes

Erythrocyte

following reaction occurs in the erythrocytes:

H2O þ CO2

⇀ ↽H2CO3

enzyme may be present in these species of animals [89].

4.7 Morphologic differences in erythrocytes of animals

shear stresses [95].

106

Erythrocytes in contact with alveoli receive oxygen which is combined with hemoglobin (oxyhemoglobin) and transported to various parts of the body. After the delivery of oxygen, the erythrocytes return CO2 combined with hemoglobin (deoxyhemoglobin) which is bluish in color to the alveoli for expiration. Hence the

⇀

The presence of COOH and C=O in piroxicam and other chemically related compounds [83] may interfere with chemistry of erythrocytes causing hemolysis and anemia. Also degradation products of some polymers, poly(lactic-co-glycolic acid), polyethylene glycol, polycaprolactone, and poly(propylene glycol) are converted to lactic acid and glycolic acid which are in turn converted to carbon dioxide and water [84] indicating that some polymers could also affect erythrocytes. Polycythemia could be confirmed by hyperpnea. Meat from an animal poisoned with potassium permanganate could react with 0.2% ethanolic benzidine changing the color of meat to dark green in 1–2 s [85], and potassium permanganate causes hyperpnea. Lowest oxygen saturation could be improved by zolpidem [86]. Erythrocytes of cow, dog, goat, horse, pig, rabbit, rat, and sheep composed greatly of cholesterol and cholesteryl esters, triglycerides, and free fatty acids are present in trace quantity. They may not be true constituents of erythrocytes, but rather contaminants from plasma lipoproteins or leucocytes. Cholesterol is 30% of cell lipid and has molar ratio with phospholipid [87] and may affect oxygen capacity of erythrocytes. Hence cow, sheep, horse, rabbit, and chicken erythrocytes are

susceptible to Vibrio vulnificus hemolysin with varying degrees of susceptibility [88] and may cause anemia and less oxygen transport. Human coagulation factor 1X (F-1X) activated by human RBCs causes coagulation activated by enzyme in the RBC membrane. However, in dog, cattle, rabbit, and sheep, coagulation did not occur except in pig when procoagulant was used. Hence coagulation activation of

Lysis of erythrocytes by toxins of cobra could cause anemia and splitting of phospholipids in equal capacity in rabbit, dog, human, and guinea pig, but not in camel and sheep erythrocytes. Phosphatide acylhydrolase is responsible for splitting of the erythrocytes. The action is via lytic factor which is hemolytic. The phospholipase readily hydrolyzes phospholipids of erythrocytes. Vipera palestinae could not lyse erythrocytes and hydrolyze phospholipids [90]. Plasma viscosity depends on plasma protein concentration [91], with cattle having 1.72 mpa s and rabbit (1.3 mpa s) with horse, dog, cat, mouse, rat, pig, and sheep having 1.3–1.7 mpa s. Man has a value lower than this range [92]. Deformability of RBCs is dependent on size and shape [93] with pig, hamster, rat, mouse, and rabbit having more deformable RBCs than sheep, horse, elephant, and dog. The deformity is characterized by RBC elongation and aggregation [94]. All these could affect oxygen transport. Non-irreversible sickle cells adhere more at normal oxygen tension, and more than 1% of the cells remained adhered to the monolayer at forces higher than physiologic

Llama, dromedary, and camel have low hematocrit value and low RBC aggregation [96]. Such RBCs may be small and elliptical in shape [97]. Nonmammalian RBCs have nucleus and microtubular bundle connected to a marginal band [98].

↽H<sup>þ</sup> þ HCO�

3 ⇀

↽H2O þ CO2 (24)

### 4.9 Anemia as a major sign of erythrocyte deformation

Causes of anemia in cats are acute blood loss, chronic inflammatory disease, renal disease, feline leukemia, immune-mediated hemolytic anemia, pure red cell aplasia, myeloproliferative syndrome, mycoplasma infection, cytauxzoonosis, iron deficiency, and nutritional deficiency. The prognosis of feline nonregenerative anemia is variable, reversible, chronic, or fatal [121]. The spleen contributes to anemia by removing the damaged erythrocytes. Hereditary spherocytosis is spectrin-deficient and ankyrin-deficient erythrocytes dependent and could cause hemolysis [122]. Glycogen storage disease could affect erythrocytes. The disease is classified as follows: Type 1 (von Gierke's disease) is caused by deficiency of glucose-6-phosphate, whereas type 2 (Pompe's disease) is generalized glycogenosis. But type 3 (limit dextrinosis) is characterized by deficiency of the amylo-1, 6-glucosidase or debrancher enzyme, and type 4 is characterized by hepatic cirrhosis, abnormal glycogen resembling amylopectin, and deficiency of amylo-1, 4-1, 6-transglucosidase. Type 5 is characterized by weakness of muscle and phosphorylase deficiency in adults, and type 6 is clinically similar to type 1, characterized by higher phosphorylase. But type 3 has the highest concentration of glycogen, in the erythrocytes, but the concentration of glycogen is normal in type 1 and 2 [123].

erythrocytes last for 100–110 days with complications including but not limited to iron overload, viral and bacterial infections, immune injury, non-Hodgkin lymphoma, and chronic lymphocytic leukemia which are some worst outcome in selected cancers [135]. Trypanosomosis, pediculosis, helminthosis, lousiness, colibacillosis, babesiosis, coccidiosis, and amoebiasis characterized by anemia in advanced condition could be treated using various species of medicinal plants. The therapeutic principles are alkaloids, tannins, saponins, glycosides, flavonoids, phenols, minerals, and vitamins [136]. Health education could lead to disappearing of blood-related diseases such as malaria [137]. Ebola affects the blood leading to hemorrhage, septic shock, and multiple organ failure [138]. This point to the need for transfusion which could not be instituted until blood and erythrocytes are assessed. Because less than 1% dense hematocrit could cause aneurysm in aged dogs,

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals

DOI: http://dx.doi.org/10.5772/intechopen.85865

Erythrocytes are red blood cells that transport oxygen from the alveoli to other parts of the body. Hence they are very vital connective tissues that play a metabolic role on the functional organ system. Its pathological features could be used for diagnosis of a myriad of metabolic, non-metabolic, infectious, noninfectious, hereditary, and non-hereditary diseases. Erythrocyte shape, size, area, and volume could be used to determine a prognosis of a disease. Erythrocytes also store some drugs invariably prolonging their half-life. Hemolysis can lead to anemia that is treated using hematonics. But severe blood loss is corrected by blood transfusion.

canine hematocrit is an accurate model for human hematocrit [139].

5. Conclusion

Author details

109

Saganuwan Alhaji Saganuwan

Federal University of Agriculture Makurdi, Nigeria

provided the original work is properly cited.

\*Address all correspondence to: pharn\_saga2006@yahoo.com

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

Plasmodium species, Babesia species, and Bartonella species can target erythrocytes directly, whereas immunogens, microbial toxins, crypt antigens, and suppression of erythropoiesis can target erythrocytes indirectly. Duffy blood group antigens, ABO blood group antigens, Knops blood group antigen, Gerbich blood group antigen, babesiosis, bartonellosis, and toxoplasmosis target RBCs primarily. Erythrocytes are targeted for immunogenic clearance of Mycoplasma pneumoniae, Haemophilus influenzae type B, Salmonella species, polyagglutination T activation, Clostridium perfringens, parvovirus B19, Epstein-Barr virus, and acquired B antigen [124]. Disorders of erythrocytes hydration are overhydration, hereditary hydrocytosis, cryohydrocytosis, dehydration, and hereditary xerocytosis which are genetic [125]. Chronic liver disease could cause anemia but requires a complex diagnostic approach [126]. Hereditary erythrocyte volume homeostasis is heterogeneous with phenotypes ranging from overhydrated to dehydrated erythrocytes usually characterized by laboratory, physiological, clinical, and genetic findings [127].

Examination of urine sediment could serve as a guide for diagnosis and management of kidney disease [128] in relation to erythrocyte disorders. Erythrocytes have linked type 2 diabetes and Alzheimer disease in human. Superimposed alterations have been observed in Alzheimer disease patients caused by oxidative stress of erythrocytes [129], suggesting that therapeutic target on RBCs could alleviate Alzheimer disease. Hence erythrocytes' mechanical properties toward microfluidics could provide a clinical correlate in diseases of erythrocytes [130]. End-stage renal disease causes alteration of erythrocytes. Therefore, erythrocytes from peritoneal dialysis patients are more prone to aggregation that may be caused by uremia, hypoproteinemia, and high oxidative stress on erythrocytes, impairing blood flow dynamics and causing inadequate microcirculatory perfusion [131]. Erythrocyte complement receptor type 1 (E-CR 1) level of expression could be used as a diagnostic marker for systemic lupus erythematosus (SLE) [132]. The level of concentration of methotrexate polyglutamate in erythrocytes is associated with alleviation of rheumatoid arthritis [133].

Blood transfusion and febrile condition could also affect morphology of erythrocytes and erythrocyte count [134]. However, 15% of cancer patients with anemia are given blood transfusion and with hemoglobin level of <9 g/dl used as index of anemia. After transfusion hemoglobin rises by 1 g/dl, and the transfused

Effects of Therapeutic and Toxic Agents on Erythrocytes of Different Species of Animals DOI: http://dx.doi.org/10.5772/intechopen.85865

erythrocytes last for 100–110 days with complications including but not limited to iron overload, viral and bacterial infections, immune injury, non-Hodgkin lymphoma, and chronic lymphocytic leukemia which are some worst outcome in selected cancers [135]. Trypanosomosis, pediculosis, helminthosis, lousiness, colibacillosis, babesiosis, coccidiosis, and amoebiasis characterized by anemia in advanced condition could be treated using various species of medicinal plants. The therapeutic principles are alkaloids, tannins, saponins, glycosides, flavonoids, phenols, minerals, and vitamins [136]. Health education could lead to disappearing of blood-related diseases such as malaria [137]. Ebola affects the blood leading to hemorrhage, septic shock, and multiple organ failure [138]. This point to the need for transfusion which could not be instituted until blood and erythrocytes are assessed. Because less than 1% dense hematocrit could cause aneurysm in aged dogs, canine hematocrit is an accurate model for human hematocrit [139].
