**3. Results**

Subject characteristics, including CD4+cell count, CD8+cell count, and CD4/CD8 ratio, weight, body mass index (BMI, in kg/m2 ), are shown in Table 1. At initial screening HIV-infected subjects were significantly lower weight and BMI compared to healthy subjects. There were insignificant changes between initial screening and after 6 months. The range of CD4+cell counts was broad, from 282 to 1830 x 106 cells/L at the initial screening and from 323 to 1687 after 6 months CD4/CD6 ratio was from 0.1 to 1.7 at the initial screening and from 0.1 to 3.4 after 6 months of using food supplements, CD8+cell counts was from 272 to 4525 at the initial screening and from 222 to 4851 after 6 months.


**Table 1.** Effect of antioxidant supplementation on body weight, body mass index and immune function in HIV patients.

Antioxidant status is shown in Table 2. At the baseline HIV-positive patients had significantly lower GSHPX and CAT concentrations compare to healthy subjects (p<0.05), but did not differ after 6 months using food supplements. There were insignificant differences in SOD and MDA measurements and α-Tocopherol concentration at the initial screening, but differed signifi‐ cantly after 6 months compare to HIV-infected and healthy individuals. Changes of biochem‐ ical measurements (alanine aminotranferase, alkaline aminotranferase, bilirubin, albumin and total protein, total holesterol and triglicerides) were not significant between groups of HIVinfected and healthy individuals as well as at the initial screening and after 6 months after use of food supplements. Additionally, two HIV-infected individuals from 26 involved in the study reported that after the use of antioxidant cocktail, gingival bleeding was stopped. One reported this symptom for two years before the study and one reports half a year this problem before study.

in plasma were measured using fluorometric method. Other measurements were also included

Using the SPSS 14.0 for Windows software standard version, statistical analyses were per‐ formed. All group data are expressed as means ± SEMs. The HIV-positive group was compared with the seronegative control subjects by using one way ANOVA. The minimal level of significance was identified at *P* < 0.05. All patients were evaluated with regard to the blood antioxidant system, specifically superoxide dismutase (SOD) and glutathione peroxidase.

Subject characteristics, including CD4+cell count, CD8+cell count, and CD4/CD8 ratio, weight,

subjects were significantly lower weight and BMI compared to healthy subjects. There were insignificant changes between initial screening and after 6 months. The range of CD4+cell counts was broad, from 282 to 1830 x 106 cells/L at the initial screening and from 323 to 1687 after 6 months CD4/CD6 ratio was from 0.1 to 1.7 at the initial screening and from 0.1 to 3.4 after 6 months of using food supplements, CD8+cell counts was from 272 to 4525 at the initial

Weight HIV-infected 26 73.1±2.1 13 74.7±2.8

BMI HIV-infected 26 22.5±0.6 13 23.0±0.8

CD4+ HIV-infected 25 698.4±74.3 21 743.6±87.4 CD8+ HIV-infected 25 1641.9±188.1 21 1341.0±216.1 CD4+/CD8 HIV-infected 25 0.6±0.1 21 0.9±0.2

**Table 1.** Effect of antioxidant supplementation on body weight, body mass index and immune function in HIV

Antioxidant status is shown in Table 2. At the baseline HIV-positive patients had significantly lower GSHPX and CAT concentrations compare to healthy subjects (p<0.05), but did not differ after 6 months using food supplements. There were insignificant differences in SOD and MDA

healthy uninfected 10 82.4±2.6 9 83.3±2.7

Healthy 10 24.7±0.7 9 25.1±0.7

), are shown in Table 1. At initial screening HIV-infected

**Baseline After 6 months**

p<0.05 p<0.05

p<0.05 NS

**n Mean±SE n Mean±SE**

such as catalase and GSHPX.

244 Pharmacology and Nutritional Intervention in the Treatment of Disease

body mass index (BMI, in kg/m2

screening and from 222 to 4851 after 6 months.

**2.3. Statistical analyses**

**3. Results**

patients.


**Table 2.** Effect of antioxidants supplementation on antioxidant enzymes, selenium, vitamin E and lipid peroxidation in HIV patients.

#### **4. Discussion**

There has been increasing interest in the application of antioxidants to many diseases as information is constantly gathered linking the development of HIV to oxidative stress [51]. Antioxidants are believed to function interactively and synergistically to neutralize reactive oxygen species (ROS). Reactive oxygen species include molecules like hydrogen peroxide; ions like the hypochlorite ion; radicals like the hydroxyl radical; and the superoxide anion, which are an ion and a radical.

The loss of CD4 T lymphocytes is a central factor in the progression of HIV infection to AIDS. The key role of these cells in regulating and amplifying the immune response means that any decline in their number results in deficits in both humoral and cell-mediated immunity [57]. Both the CD4 percentage and the CD4:CD8 ratio are also affected by changes in the number of CD8 cells, which tends to rise through the course of HIV infection [58].This study demon‐ strates that after supplementation, there is an increase in CD4 T cells in HIV patients. Several research studies have indicated that the apoptosis of CD4 cells contributing to HIV progression does not result solely from HIV infection, but largely from antioxidant imbalances in the host [43, 59, 60]. Activation of latent HIV state can be stimulated in the presence of reactive oxygen species (ROS) through the stimulation of oxygen-responsive transcription factors, specifically

Impact of CoQ10, L-Carnitine and Cocktail Antioxidants on Oxidative Stress Markers in HIV Patients — Mini Review…

http://dx.doi.org/10.5772/58415

247

The mean serum malondialdehyde (MDA) concentrations in this study were significantly elevated in HIV infected patients. Serum concentration of total serum antioxidant status (TAS) was increased after supplementation. Our data indicate that severe oxidative stress occurs in the serum of HIV patients in comparison with controls ones and the inclusion of antioxidants in the therapeutic approach in managing HIV patients may prevent the additional free radicals damage. It has been shown that cells infected with the HIV undergo a significant amplification

<sup>−</sup> generation. This phenomenon combined with a deficiency in key antioxidant enzymes (SOD and CAT) and a decreased concentration of the antioxidant vitamins, may lead to severe oxidative stress in HIV-infected patients. Consequently these conditions may in turn be responsible for the DNA base modifications observed in this study [43]. Serum MDA adducts also tended to correlate inversely with expression of CD127 on T cells was shown [61]. Study in placenta, umbilical cord blood and infant blood in HIV/ART-exposed infants compared with uninfected controls [62] showed that placental mitochondria malondialdehyde (MDA) concentrations and mtDNA content in placenta and cord blood were similar between groups. Supplementation with antioxidant vitamins prevents oxidative modification of DNA in lymphocytes of HIV-infected patients [44]. Furthermore, as an antioxidant, vitamin E [63]and atherosclerotic lesions contain oxidized lipids [64], therefore, supplementation with vitamin E would decrease heart disease risk. It has been reported that α-tocopherol concentrations in serum are regulated by the α-tocopherol transfer protein and are dependent on serum lipid concentrations because α-tocopherol is non-specifically transported by lipoproteins [63]. Serum micronutrient concentrations along with surrogate markers of atherosclerosis in a cohort of HIV infected adults were studied [65](Falcone et al. 2010), the highest tertile of serum vitamin E concentration was associated with higher common and internal carotid intimamedia thickness (c-IMT) and coronary artery calcium (CAC) scores [65]. The authors concluded that elevated serum vitamin E values may increase the risk of cardiovascular complications in

There appears to be a possible role for antioxidants supplements. However, these supplements cannot effectively eliminate HIV signs and symptoms and the optimal dosage of these nutrients

NF-kB, which induces HIV replication in the infected T-lymphocyte.

of O2

HIV-infected adults [65].

is (whether used alone or in combination) has to defined

All subjects from the current study are at low serum selenium level (which is about 80 – 120 µg /L in Europe), and stayed as that even after use of antioxidants supplements, including selenium. Similar trend was also notice in the selenoenzyme glutathione peroxidase (GSHPx) level among HIV patients. Low serum selenium was defined as a serum level ≤ 85 µg/l [52]. Selenium deficiency, more than any other nutrient, has been documented to correlate with progression and mortality of HIV [53]. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS [54]. When taken as a supplement, selenium modulates the cellular response to oxidative stress, inducing a faster restoration of the endogenous antioxidative defence system against the production of reactive oxygen species [55]. Glutathion peroxidase controls the interacellular level of hydrogen peroxide, reducing the formation of reactive oxygen species that can induce lipid peroxidations with consequent damage to the cellular membranes [56].

**Figure 3.** Selenium level of HIV infected individuals and healthy subjects (μ/g Hb)

The loss of CD4 T lymphocytes is a central factor in the progression of HIV infection to AIDS. The key role of these cells in regulating and amplifying the immune response means that any decline in their number results in deficits in both humoral and cell-mediated immunity [57]. Both the CD4 percentage and the CD4:CD8 ratio are also affected by changes in the number of CD8 cells, which tends to rise through the course of HIV infection [58].This study demon‐ strates that after supplementation, there is an increase in CD4 T cells in HIV patients. Several research studies have indicated that the apoptosis of CD4 cells contributing to HIV progression does not result solely from HIV infection, but largely from antioxidant imbalances in the host [43, 59, 60]. Activation of latent HIV state can be stimulated in the presence of reactive oxygen species (ROS) through the stimulation of oxygen-responsive transcription factors, specifically NF-kB, which induces HIV replication in the infected T-lymphocyte.

**4. Discussion**

246 Pharmacology and Nutritional Intervention in the Treatment of Disease

are an ion and a radical.

damage to the cellular membranes [56].

Selenium ug/L

 80 70

60

50

40

30

**Figure 3.** Selenium level of HIV infected individuals and healthy subjects (μ/g Hb)

There has been increasing interest in the application of antioxidants to many diseases as information is constantly gathered linking the development of HIV to oxidative stress [51]. Antioxidants are believed to function interactively and synergistically to neutralize reactive oxygen species (ROS). Reactive oxygen species include molecules like hydrogen peroxide; ions like the hypochlorite ion; radicals like the hydroxyl radical; and the superoxide anion, which

All subjects from the current study are at low serum selenium level (which is about 80 – 120 µg /L in Europe), and stayed as that even after use of antioxidants supplements, including selenium. Similar trend was also notice in the selenoenzyme glutathione peroxidase (GSHPx) level among HIV patients. Low serum selenium was defined as a serum level ≤ 85 µg/l [52]. Selenium deficiency, more than any other nutrient, has been documented to correlate with progression and mortality of HIV [53]. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS [54]. When taken as a supplement, selenium modulates the cellular response to oxidative stress, inducing a faster restoration of the endogenous antioxidative defence system against the production of reactive oxygen species [55]. Glutathion peroxidase controls the interacellular level of hydrogen peroxide, reducing the formation of reactive oxygen species that can induce lipid peroxidations with consequent

N = 44 38

HIV infected Healthy

58

59

The mean serum malondialdehyde (MDA) concentrations in this study were significantly elevated in HIV infected patients. Serum concentration of total serum antioxidant status (TAS) was increased after supplementation. Our data indicate that severe oxidative stress occurs in the serum of HIV patients in comparison with controls ones and the inclusion of antioxidants in the therapeutic approach in managing HIV patients may prevent the additional free radicals damage. It has been shown that cells infected with the HIV undergo a significant amplification of O2 <sup>−</sup> generation. This phenomenon combined with a deficiency in key antioxidant enzymes (SOD and CAT) and a decreased concentration of the antioxidant vitamins, may lead to severe oxidative stress in HIV-infected patients. Consequently these conditions may in turn be responsible for the DNA base modifications observed in this study [43]. Serum MDA adducts also tended to correlate inversely with expression of CD127 on T cells was shown [61]. Study in placenta, umbilical cord blood and infant blood in HIV/ART-exposed infants compared with uninfected controls [62] showed that placental mitochondria malondialdehyde (MDA) concentrations and mtDNA content in placenta and cord blood were similar between groups. Supplementation with antioxidant vitamins prevents oxidative modification of DNA in lymphocytes of HIV-infected patients [44]. Furthermore, as an antioxidant, vitamin E [63]and atherosclerotic lesions contain oxidized lipids [64], therefore, supplementation with vitamin E would decrease heart disease risk. It has been reported that α-tocopherol concentrations in serum are regulated by the α-tocopherol transfer protein and are dependent on serum lipid concentrations because α-tocopherol is non-specifically transported by lipoproteins [63]. Serum micronutrient concentrations along with surrogate markers of atherosclerosis in a cohort of HIV infected adults were studied [65](Falcone et al. 2010), the highest tertile of serum vitamin E concentration was associated with higher common and internal carotid intimamedia thickness (c-IMT) and coronary artery calcium (CAC) scores [65]. The authors concluded that elevated serum vitamin E values may increase the risk of cardiovascular complications in HIV-infected adults [65].

There appears to be a possible role for antioxidants supplements. However, these supplements cannot effectively eliminate HIV signs and symptoms and the optimal dosage of these nutrients is (whether used alone or in combination) has to defined
