**3. Results**

## **3.1 Liver tissue**

The control sections of the liver showed normal histological features with the hepatic lobules showing irregular hexagonal boundary defined by portal tract and sparse collagenous tissues. The hepatic portal veins, bile ductules and hepatic artery within the portal tract were all visible (Figure 1).

The treatment sections of the liver showed some histological changes that were at variance with those obtained in the control. There were evidence of dilatations of the central veins, which contained lysed red blood cells and cyto-architectural distortions of the hepatocytes and centrilobular haemorrhagic necrosis. There were atrophic and degenerative changes with the group that received 1.43mg/kg body weight of Sildenafil citrate more (Figure 2, 3 & 4).

Fig. 1. Control section of the liver. Group 'D' (Mag. X400)

Fig. 2. Photomicrograph of the liver showing in the treatment groups 'A' that received 0.25mg/kg body weight of Sildenafil citrate. It shows portal tract and sparse collagenous tissues. The liver sinusoid and central veins were visible (Mag. x400)

Fig. 3. Photomicrograph of the liver showing in the treatment groups 'B' that received 0.70mg/kg body weight of Sildenafil citrate. There were atrophic and degenerative changes around the hepatocytes and central vein, which was dilated and contained lysed red blood cell (Mag. X400).

Fig. 4. Photomicrograph of the liver showing in the treatment groups 'C' that received 1.43mg/kg body weight of Sildenafil citrate. There were marked atrophic and degenerative changes around the hepatocytes and lysed red blood cell containing dilated central vein (Mag. X400).

#### **3.2 Kidney tissue**

120 Sexual Dysfunctions – Special Issue

The control sections of the liver showed normal histological features with the hepatic lobules showing irregular hexagonal boundary defined by portal tract and sparse collagenous tissues. The hepatic portal veins, bile ductules and hepatic artery within the

The treatment sections of the liver showed some histological changes that were at variance with those obtained in the control. There were evidence of dilatations of the central veins, which contained lysed red blood cells and cyto-architectural distortions of the hepatocytes and centrilobular haemorrhagic necrosis. There were atrophic and degenerative changes with the

group that received 1.43mg/kg body weight of Sildenafil citrate more (Figure 2, 3 & 4).

Fig. 2. Photomicrograph of the liver showing in the treatment groups 'A' that received 0.25mg/kg body weight of Sildenafil citrate. It shows portal tract and sparse collagenous

tissues. The liver sinusoid and central veins were visible (Mag. x400)

**3. Results** 

**3.1 Liver tissue** 

portal tract were all visible (Figure 1).

Fig. 1. Control section of the liver. Group 'D' (Mag. X400)

The control sections of the kidneys showed normal histological features. The section indicated a detailed cortical parenchyma and the renal corpuscles appeared as dense rounded structures with the glomerulus surrounded by a narrow Bowman's spaces (Figure 5)

The kidneys of the animals in group 'A' treated with 0.25mg/kg of Sildenafil citrate revealed some level of cyto-architectural distortion of the cortical structures as compared to the control (Figure 6)

The Effects of Sildenafil Citrate on the Liver

and Kidneys of Adult Wistar Rats (*Rattus norvegicus*) – A Histological Study 123

Fig. 7. Photomicrograph of the Kidney showing in the treatment groups 'B' that received 0.70mg/kg body weight of Sildenafil citrate mild to moderate distortion of cyto-architecture of the renal cortical structures with mild degenerative and atrophic changes (Mag. X400)

Fig. 8. Photomicrograph of the Kidney showing in the treatment groups 'B' that received 1.43mg/kg body weight of Sildenafil citrate marked distortion of cyto-architecture of the renal cortical structures, and degenerative and atrophic changes. There were vacuolations appearing in the stroma and loss of renal corpuscles which were less identified and the

Table 1 below shows the mean and standard deviation of each group for the different components. The table revealed that experimental group C (Exp. C) has the highest mean for components: Total Protein, Albumin, ALT and AST. The Control group had the least

Table 2 shows the analysis of variance for the four groups for the five components. The results revealed that the difference between the means of the four groups for each

The result of this experiment revealed that Sildenafil citrate consumption caused significant (P<0.05) increase in functional nephrotoxicity indicators such as BUN and Serum creatinin

in Sildenafil citrate-treated rats compared with control (Table 3).

Bowman's spaces were sparsely distributed.

mean for all the components.

component is significant (*P* <0.0001).

Fig. 5. Control section of the Kidney. Group 'D' (Mag. X400)

Fig. 6. Photomicrograph of the Kidney showing in the treatment groups 'A' that received 0.25mg/kg body weight of Sildenafil citrate showing some level of cyto-architectural distortion of the cortical structures (Mag. X400)

The kidney sections of animals in group 'B' treated with 0.70mg/kg of Sildenafil citrate revealed mild to moderate distortion of cyto-architecture of the renal cortical structures with mild degenerative and atrophic changes. The kidney sections of animals in group 'C' treated with 1.43mg/kg of Sildenafil citrate revealed marked distortion of cyto-architecture of the renal cortical structures, and degenerative and atrophic changes. There were vacuolations appearing in the stroma and loss of renal corpuscles which were less identified and the Bowman's spaces were sparsely distributed as compared to the control group 'D' (Figure 7)

Fig. 6. Photomicrograph of the Kidney showing in the treatment groups 'A' that received 0.25mg/kg body weight of Sildenafil citrate showing some level of cyto-architectural

The kidney sections of animals in group 'B' treated with 0.70mg/kg of Sildenafil citrate revealed mild to moderate distortion of cyto-architecture of the renal cortical structures with mild degenerative and atrophic changes. The kidney sections of animals in group 'C' treated with 1.43mg/kg of Sildenafil citrate revealed marked distortion of cyto-architecture of the renal cortical structures, and degenerative and atrophic changes. There were vacuolations appearing in the stroma and loss of renal corpuscles which were less identified and the Bowman's spaces were sparsely distributed as compared to the control group 'D' (Figure 7)

Fig. 5. Control section of the Kidney. Group 'D' (Mag. X400)

distortion of the cortical structures (Mag. X400)

Fig. 7. Photomicrograph of the Kidney showing in the treatment groups 'B' that received 0.70mg/kg body weight of Sildenafil citrate mild to moderate distortion of cyto-architecture of the renal cortical structures with mild degenerative and atrophic changes (Mag. X400)

Fig. 8. Photomicrograph of the Kidney showing in the treatment groups 'B' that received 1.43mg/kg body weight of Sildenafil citrate marked distortion of cyto-architecture of the renal cortical structures, and degenerative and atrophic changes. There were vacuolations appearing in the stroma and loss of renal corpuscles which were less identified and the Bowman's spaces were sparsely distributed.

Table 1 below shows the mean and standard deviation of each group for the different components. The table revealed that experimental group C (Exp. C) has the highest mean for components: Total Protein, Albumin, ALT and AST. The Control group had the least mean for all the components.

Table 2 shows the analysis of variance for the four groups for the five components. The results revealed that the difference between the means of the four groups for each component is significant (*P* <0.0001).

The result of this experiment revealed that Sildenafil citrate consumption caused significant (P<0.05) increase in functional nephrotoxicity indicators such as BUN and Serum creatinin in Sildenafil citrate-treated rats compared with control (Table 3).

The Effects of Sildenafil Citrate on the Liver

**4. Discussion** 

conditions (Farber et al, 1981).

and Kidneys of Adult Wistar Rats (*Rattus norvegicus*) – A Histological Study 125

The results of the histological studies revealed that with increasing dose of Sildenafil citrate consumption, there were varying degrees of dilatations of the central vein of the liver which contained lysed red blood cells in the treatment group compared to the control sections of the liver, and as well as varying degree of cyto-architectural distortion and reduction in the number of renal corpuscle in the kidneys of the treated groups compared to the control sections of the kidneys. This suggests that the distortion of the cyto-architecture of the liver could be associated with functional changes that may be detrimental to the health of the rats. The proliferating cells of the liver, which produce red and white blood cells, are

As a result of the distortion and dilatation of the hepatocytes and their central vein, the haematopoietic function of the liver may have been highly affected as a result of probable toxic effect of Sildenafil citrate. This was further buttressed by the increase in the liver enzymes obtained in the test group. In addition, total protein and albumin increased in this study the increase in total protein may be due to the fact that Sildenafil citrate was given for a short period of time. The resultant effect is acute toxicity leading to enhanced hepatocellullar activity and increase in globulin and albumin components of the protein .However, with prolonged usage, hepatic necrosis is likely to occur with a resultant low albumin levels. There were several diffuse degeneration and necrosis of the tubular epithelial cells in the kidneys of the treated animals. The degenerative and atrophic changes where observed more

Control 14.38±2.5 0.47±0.21 Experimental group A (0.25mg/kg) 28.7±4.63 2.3±0.23 Experimental group B (0.70mg/kg) 55±0.72 3.2±0.99 Experimental group C (1.43mg/kg) 69±0.33 3.8±2.62

Table 3. Effects of Sildenafil citrate consumption on BUN and Scr concentration

normally found between the hepatic cells and the walls of the vessels (Singh, 1997).

in the kidneys of rats that received the highest dose (1.43mg/kg) of Sildenafil citrate.

(Perry, 1980), may also account for their toxicity when the dosage is abused.

It may be inferred from the present results that higher doses of Sildenafil citrate consumption may have resulted in degenerative and atrophic changes observed in the renal corpuscle. The possible deduction from these results is that secondary metabolites, which are largely responsible for therapeutic or pharmacological activities of medicinal plants

Pathological or accidental cell death is regarded as necrotic and could result from extrinsic insults to the cell as osmotic thermal, toxic and traumatic effect (Farber et al, 1981). Physiological cell death is regarded as apoptotic and organized programmed cell death (PCD) that is mediated by active and intrinsic mechanisms. The process of cellular necrosis involves disruption of membranes, as well as structural and functional integrity. Cellular necrosis is not induced by stimuli intrinsic to the cells as in programmed cell death (PCD), but by an abrupt environmental perturbation and departure from the normal physiological

Cellular degeneration has been reported to result in cell death, which is of two types, namely apoptotic and necrotic cell death. These two types differ morphologically and biochemically (Wyllie, 1980). Pathological or accidental cell death is regarded as necrotic and could result

BUN (mg/dl) Scr (mg/dl)


Table 1. Descriptive statistics, protein and some liver enzymes assay of groups.


#### *P* <0.0001

Table 2. Analysis of Variance (ANOVA) of the Four Groups


Table 3. Effects of Sildenafil citrate consumption on BUN and Scr concentration
