الفهرس 
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Abstract
The present study is concerned with the evaluation of the protective effect of aminoguanidine, enalapril and nicorandil and their combinations against oxidative stress in diabetic rats.
Groups of rats, each of 6 animals, were used. In the first set of experiments, to induce diabetes, animals of groups I to VII were treated with a single dose of STZ 65 mg/kg intraperitoneally.
Diabetes was considered to have been induced when the blood glucose level was higher than 250 mg/dl which was confirmed 48 hours after STZ administration by determination of plasma glucose level in blood sample withdrawn from the retro-orbital venous plexus and measuring plasma glucose level by using blood glucose kits. Group I (STZ- treated group) considered as a control for groups II to VII.
Animals of groups II, III and IV were treated respectively with 50 mg/kg aminoguanidine intraperitoneally, 10mg/kg enalapril intraperitoneally and 0.1mg/kg nicorandil orally, 48 hours after STZ administration.
In the second set of experiments, animals of groups V, VI and VII were treated respectively with a combination of 50 mg/kg aminoguanidine intraperitoneally and 10mg/kg enalapril intraperitoneally, combination of 50 mg/kg aminoguanidine intraperitoneally and 0.1mg/kg nicorandil orally and a combination of 10mg/kg enalapril intraperitoneally and 0.1mg/kg nicorandil orally, 48 hours after STZ administration.
Additional groups of rats (non diabetic) were treated with 50 mg/kg aminoguanidine intraperitoneally, 10mg/kg enalapril intraperitoneally, 0.1mg/kg nicorandil orally.
The control group of animals was treated likewise with the pure vehicles (Sodium citrate and Saline).
All of the above groups were received their treatment for one month. After the end of the treatment period, animals were sacrificed. Blood samples, kidney and liver tissues were obtained from each animal for biochemical measurements of SOD, catalase, MDA, GSH and nitrite. Besides, plasma glucose level and histopathological examination of kidney and liver tissues were performed.
Treatment of the rats with 65 mg/kg STZ intraperitoneally led to a significant increase in the blood glucose level. Plasma, kidney and liver tissues showed significant increase in MDA and nitrite levels and significant decrease in SOD, catalase and GSH levels. Our histopathological results revealed that STZ produced kidney and liver damage.
Treatment of the diabetic rats with aminoguanidine, enalapril, nicorandil and their combinations for one month produced insignificant change in blood glucose level in comparison with STZ-treated group. Also, treatment of the non-diabetic rats with aminoguanidine, enalapril and nicorandil for one month produced insignificant change in blood glucose level in comparison with control group.
The results showed that the intraperitoneal injection of aminoguanidine to the diabetic rats for one month produced significant increase in plasma, kidney and liver tissues SOD, catalase and GSH and significant decrease in plasma, kidney and liver tissues MDA and nitrite and improvement of the histopathological structures of both kidney and liver tissues compared to STZ-treated group.
Administration of enalapril intraperitoneally for one month to the diabetic rats produced significant increase in plasma, kidney and liver tissues SOD, catalase and GSH levels and significant decrease in plasma, kidney and liver tissues MDA and nitrite levels compared to STZ-treated group. Also, it improved the histopathological structures of both kidney and liver compared to STZ-treated group.
Administration of nicorandil orally for one month to the diabetic rats produced significant increase in plasma, kidney and liver tissues SOD and GSH levels and significant decrease in plasma, kidney and liver tissues MDA level compared to STZ-treated group. However, it produced insignificant change in plasma, kidney and liver tissues catalase and nitrite levels compared to STZ-treated group. Histopathologically, administration of nicorandil improved the structures of both kidney and liver compared to STZ-treated group.
Combined administration of aminoguanidine and enalapril for one month to the diabetic rats produced significant increase in plasma, kidney and liver tissues SOD, catalase and GSH levels and significant decrease in plasma, kidney and liver tissues MDA and nitrite levels compared to STZ-treated group. This combination, compared to STZ + aminoguanidine group, produced insignificant change in plasma, kidney and liver tissues SOD, catalase, MDA and GSH and kidney and liver tissues nitrite levels but produced significant decrease in plasma nitrite level. Compared to STZ + enalapril group, the combination produced significant increase in plasma, kidney and liver tissues SOD, plasma and kidney tissue catalase and plasma GSH but produced significant decrease in plasma MDA and plasma nitrite levels and insignificant change in liver tissue catalase, kidney and liver tissues MDA, GSH and nitrite. Also, it improved the histopathological structures of both kidney and liver tissues.
As for combined administration of aminoguanidine and nicorandil for one month to the diabetic rats, it produced significant increase in plasma, kidney and liver tissues SOD, catalase and GSH levels and significant decrease in plasma, kidney and liver tissues MDA and nitrite levels compared to STZ-treated group. This combination, compared to STZ + aminoguanidine group, produced insignificant change in plasma, kidney and liver tissues SOD, MDA and GSH, plasma catalase, and plasma and liver tissue nitrite but produced significant decrease in kidney and liver tissues catalase and kidney tissue nitrite. Compared to STZ + nicorandil group, the combination produced significant increase in kidney and liver tissues SOD, plasma, kidney and liver tissues catalase and plasma and liver tissue GSH and produced significant decrease in plasma and kidney tissue MDA and plasma, kidney and liver tissues nitrite. No significant change in plasma SOD, liver tissue MDA and kidney tissue GSH were recorded. Our histopathological results revealed improvement in both kidney and liver structures.
Combined administration of enalapril and nicorandil for one month to the diabetic rats produced significant increase in plasma and kidney and liver tissues SOD, catalase and GSH levels and significant decrease in plasma, kidney and liver tissues MDA and plasma and kidney tissue nitrite levels. No significant change in liver tissue nitrite level compared to STZ-treated group. This combination, compared to STZ + enalapril group, produced insignificant change in plasma and liver tissue SOD, plasma, kidney and liver tissues catalase, MDA, and GSH levels and kidney tissue nitrite but produced significant increase in kidney tissue SOD and plasma and liver tissue nitrite. Our results revealed that the combination, Compared to STZ + nicorandil group, produced significant increase in plasma, kidney and liver tissues catalase, plasma GSH and produced significant decrease in kidney tissue MDA and plasma, kidney and liver tissues nitrite. No significant alteration in plasma, kidney and liver tissues SOD, plasma and liver tissue MDA and kidney and liver tissues GSH levels were observed. Histopathologically, the combination improved both kidney and liver structures.
It is of interest that, aminoguanidine, enalapril and nicorandil by themselves produced no significant changes in plasma, kidney and liver tissues SOD, catalase, MDA, GSH and nitrite levels compared to control group. Also they did not induce structural disturbance in both kidney and liver tissues in this study.
Results of this investigation led to the following conclusions:
Aminoguanidine, enalapril, nicorandil and their combinations have the ability to protect against oxidative stress induced by streptozotocin.
The ability of aminoguanidine, enalapril, nicorandil and their combinations to provide this effect is positively correlated with their anti-oxidant activities.