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American Journal of Pharmacology and Toxicology

Year: 2009  |  Volume: 4  |  Issue: 2  |  Page No.: 22 - 28

Effects of Leaf Extract of Urtica pilulifera L. on Male Reproductive System of Streptozotocin-Diabetic Rats

Fawzi Irshaid and Kamal Mansi

Abstract

Problem statement: Urtica pilulifera L. (Urticaceae), has long been used for the treatment of various aliments including diabetes. Diabetes is a metabolic disorder characterized by hyperglycemia which has a deleterious effect on all systems including reproductive system of animals. Therefore, the current study was designed to investigate the effects of Urtica pilulifera on the reproductive system of diabetic rats. Approach: Forty male rats were evenly divided into four groups: Group I consisted of non-diabetic rats that received only the vehicle; group II-IV was injected intraperitonially with a single dose of streptozotocin (STZ) of 70 mg kg-1; groups III and IV were given methanol extract of Urtica pilulifera orally, 3 days after the STZ injection, at daily doses of 1.0 and 2.0 g kg-1, respectively. After 4 weeks of treatments, all the rats were sacrificed. Results: Administration of 70 mg kg-1 of streptozotocin to male rats induced diabetes and significantly reduced the body and sex organ weights, testosterone levels, sperm count and motility and significantly increased the glucose levels and water and food intake. By contrast, rats given the Uritica pilulifera methanol extract had significantly improved body weight gain, whereas the glucose levels, water and food intake significantly improved in treated diabetic male rats. In addition, this extract improved the reproductive system of the diabetic male rats by significantly increasing the testis and epididymis weights, testosterone levels, sperm count and motility. Conclusion/Recommendations: We concluded that the adverse effects of STZ-diabetes on reproductive system of male rats can be reversed by treatment with Urtica pilulifera leaf extract; and this leaf extract exhibits antihyperglycemic and spermatogenic activities. Based on these findings, we suggested the possible utilization of Urtica pilulifera extracted as a therapy to prevent the development of diabetes in later life and improved the performance of male reproductive system in animals and humans.

Table 1). In contrast, the untreated diabetic group (II) lost an average of 19 g after 4 weeks (p<0.05). Treatment with U. pilulifera resulted in significant weight gain to levels approaching the control group (Groups III and IV, versus Group I).

Effect on water and food intake: Water and food intake in untreated diabetic group were significantly higher than that of the control group (Table 2 and 3). On other hand, there were significant decreases in water and food intake in treated diabetic groups compared to untreated diabetic group during the entire period of the experiment (p<0.05). The two treated diabetic groups also consumed more food when compared to control group during the entire study period.

Table 1: Effect of oral administration of U. pilulifera extract for four weeks on body weight (g) in STZ-diabetic male rats
Values are the mean values ± standard deviation of 10 rats; *: Statistically significant when compared to control group (I) at p<0.05; **: Statistically significant when compared to untreated diabetic group (II) at p<0.05

Table 2: Effect of oral administration of U. pilulifera extract for four weeks on water intake (mL day-1) in STZ-diabetic male rats
Values are the mean values ± standard deviation of 10 rats; *: Statistically significant when compared to control group (I) at p<0.05; **: Statistically significant when compared to untreated diabetic group at p<0.05

Table 3: Effect of oral administration of U. pilulifera extract for four weeks on food intake (g day-1) in STZ-diabetic male rats
Values are the mean values ± standard deviation of 10 rats; *: Statistically significant when compared to control group (I) at p<0.05; **: Statistically significant when compared to untreated diabetic group at p<0.05

Table 4: Effect of oral administration of U. pilulifera extract for four weeks on serum glucose concentration (mg dL-1) in STZ-diabetic male rats
Values are the mean values ± standard deviation of 10 rats; *: Statistically significant when compared to control group (I) at p<0.05; **: Statistically significant when compared to untreated diabetic group (II) at p<0.05

Table 5: Effect of oral administration of U. pilulifera extract for four weeks on serum testosterone level (ng mL-1) in STZ-diabetic male rats
Values are the mean values ± standard deviation of 10 rats; *: Statistically significant when compared to control group (I) at p<0.05; **: Statistically significant when compared to untreated diabetic group (II) at p<0.05

The average food intake of treated diabetic group (II) and (III) were 18.3 and 20.2 g, respectively, whereas that of control group was 12.4 g at the end of the experimental period (Table 2). These increases in food intake among treated groups (III and IV) were statistically significant when compared with that of the control group (p<0.05). Along the same line (Table 3), the average water intake of group (II) and (III) were 77.3 and 85.7 mL day-1, respectively, at the end of the experimental period, which was significantly more than in the control group, which was 24.4 mL day-1.

Effect on serum glucose concentration: An increase in serum glucose concentration (mg dL-1) was recorded in untreated diabetic group, relative to the control group (Table 4). After four weeks, the serum glucose concentration in untreated diabetic group increased to 357.6 mg dL-1. In treated diabetic rats (Groups III/IV), the serum glucose concentration increased to 251.5 and 231.3 mg dL-1, respectively, after four weeks, which was significantly less than in the untreated diabetic group (p<0.05).

Effect on serum level of testosterone: The diabetic rats experienced a decrease in serum testosterone levels, to 62% of the levels of the control rats at the third week and 71% at the fourth week (Table 5). Treatment of the diabetic rats with U. pilulifera (Groups III/IV) caused a significant increase in the levels of testosterone in a dose-dependent manner (p<0.05).

Table 6: Effect of oral administration of U. pilulifera extract after 4 weeks on testis and epididymis weights, sperm count and motility in STZ-diabetic male rats
Values are the mean values ± standard deviation of 10 rats; *: Statistically significant when compared to control group (I) at p<0.05; **: Statistically significant when compared to untreated diabetic group (II) at p<0.05

Effect on sex organ weights, sperm count and motility of male rats: The data in Table 6 shows that the testes and epididymis weights of the untreated diabetic group were significantly lowered at the fourth week by 41.3 and 60.9%, respectively, as compared with those of the control group (p<0.05). Treatment of the diabetic male rats with U. pilulifera (Groups III/IV) caused a significant increase in testis and epididymis weights (p<0.05). Along the same line, sperm count and motility of untreated diabetes group also significantly lowered, as compared with those of the control group. This reduction was statistically significant (p<0.05). On other hand, administration of U. pilulifera methanol extract for 4 weeks showed a significant improvement in the sperm count and motility of treated diabetic groups (Groups III/IV) in a dose-dependent manner (p<0.05). However, the sperm count and motility of the treated diabetic groups (III and IV) were still lower than those of control group I.

Discussion

Insulin is well known as an anabolic hormone that plays a vital role in maintenance of body growth and overall body metabolism. Partial or complete insulin deficiency in diabetic humans as well as in induced-diabetic experimental animals appears to have adverse effects on all organs, including reproductive organs[9,11,20]. This present study was amid to evaluate the effects of methanol extract of U. pilulifera on reproductive organs of STZ-induced diabetes male rats. Our current data indicate that blood glucose level, water and food intake significantly increased, but body weight gain decreased after injection of STZ in male rats. These findings are consistent with previous study which indicated that the cytotoxic action of STZ is mediated by the formation of free radicals such as superoxide and hydroxyl radicals[8,21-23]. The action of these free radicals can cause rapid destruction of ß-cells of pancreas, resulting in partial or complete loss of insulin production and leading to the development of hyperglycemia and its complications. These changes are also the normal effect of diabetes mellitus. Furthermore, our results also showed that administration of U. pilulifera extract resulted in lowering of blood glucose level, water and food intake significantly and improving body weight gaining in a dose-dependent manner in diabetic male rats with no apparent side effect. This confirms the study of Kavalali et al.[3] who reported that a significant anti-diabetic effect was observed in STZ-diabetic rats at the dose of 100 mg kg-1 of lectin isolated from U. pilulifera after administration for 30 days. However, the mechanism of action of this compound has not been reported.

Furthermore, our study also shows that injection of male rats with STZ compound reduced weights of testis and epididymis, testosterone production and sperm motility and count, suggesting a toxic effect of STZ in the structural and functional integrity of testicular tissues. Our results are in agreement with previous published reports which revealed that induction of diabetes by high doses of STZ in male testes lead to reduction in testosterone production, suggesting a decrease in the function of both Leydig (testosterone producing cell) and Sertoli (spermatogenesis), which might be caused by a reduction in insulin secretion[7,9]. An early study also indicated that glucose oxidation and utilization are important means by which spermatozoa derives energy for their motility[24]. Taken together, the negative impact of STZ on reproductive organ of male rats in this study probably can be explained by a reduction in insulin secretion, leading to development of hyperglycemia as suggested above. This notion is consistent with and supported by other studies which reported that hyperglycemia induces oxidative stress, can cause inactivation of antioxidant defense enzymes and increase production of free radicals and such conditions result in increase glycosylation and oxidation of proteins and membrane dysfunction of target cells, especially the β-cells of pancreas[25,26].

Interestingly, our current study also shows for the first time that oral administration of U. pilulifera extract for four weeks improved the production of testosterone, weights of testis and epididymis, sperm motility and count in STZ-diabetic male rats. Recently, methanol extract of different parts of U. pilulifera extracts were found to exhibit powerful antioxidant activity against various oxidative systems in vivo[27]. The antioxidant activity of these extracts has been attributed to the reduction of lipid peroxidation and elevation of antioxidant enzyme activities. Additionally, recent studies also indicated that treatment with antioxidant compounds isolated from natural products may be important for ß-cell function and growth, reducing the complications of diabetes by inhibiting the formation of free radicals in induced-diabetic animals[22,23]. Taken together, our results combined with those of previous findings allow us to suggest that the leaf extract of U. pilulifera contains bioactive compounds with antioxidant activities which might reverse the toxic action of STZ and thus restoring β-cell integrity and metabolic function which are responsible for synthesis of insulin. However, it is also important to note that our data lack direct evidence that links free radical inhibition to the improvement of function and growth of β-cells of pancreas and reproductive cells of diabetic male rats. In addition, these positive effects are probably due to the presence of bioactive compounds with antidiabetic and/or insulinomimetic activity resulting in an increase in glucose utilization and metabolism in peripheral tissues as reported by Kavalali et al.[3]. We can not also exclude the possibility that these bioactive compounds might cause glucose level to normalize and/or drive glucose metabolism by some other unknown mechanisms. Such mechanisms may result in reduction of hyperglycemia which might lead to resolution of the other down-stream pathologic effects. Therefore, additional experiments will be needed to characterize the details of the mechanism(s) by which U. pilulifera normalize the glucose level and/or affects the function and growth of both pancreas and reproductive organs of diabetic male rats.

CONCLUSION

In conclusion, the present study indicates that administration of STZ in rats induces hyperglycemia and exhibits a number of defects in reproductive organs of male rats. On other hand, methanol extract of U. pilulifera exhibits antihyperglycemic and spermatogenic activities in STZ-induced diabetic male rats. These activities are responsible, at least partly, for these improvements that have been seen in the performance of male reproductive system of diabetic rats. In addition, these findings suggest the possible utilization of U. pilulifera extract as a therapy to prevent the development of diabetes in later life and improve the performance of male reproductive system in animals and humans.

Acknowledgment

This research has been partially supported by grants 2008/4419 from the Deanship of Scientific Research at Al al-Bayt University. The authors would, therefore, like to appreciate the financial assistance and express our gratitude to the University.

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