20-Hydroxyecdysone Protects Pancreatic Islets and Liver in Streptozotocin-lnduced Diabetic Rats

Abstract

Objective: 20-hydroxyecdysone (20HE), a steroid hormone that modulates molting response in insects exerts many pharma­cological effects in mammals, most of which appear beneficial. The aim of this study was to investigate whether 20HE is able to reduce the destruction of beta-cells of the islets of Langerhans and ame­liorate hyperglycemia induced changes in liver tissue in strepto­zotocin (STZ)-induced rat model of diabetes. Methods: An experimental model of diabetes was induced in rats by the administration of 35 mg/kg STZ intraperitoneally for 4 consecutive days. 20HE was administered orally at a dose of20 mg/ kg body weight for four weeks, starting from the last day of STZ administration. Pancreas tissue sections were analyzed by hema­toxylin and eosin staining and immunohistochemical staining with insulin. Estimation of oxidative damage of DNA and lipids in the liver were detected by comet assay and thiobarbituric acid-re­active substance assay, respectively. Liver sections were analyzed by hematoxylin/eosin and Masson's trichrome staining. Results: Diabetic rats treated with the 20HE displayed several improved biochemical parameters in the circulation: reduced hy­perglycemia, lower triglyceride concentration and reduced glycat­ed hemoglobin. The administration of 20HE to diabetic rats also led to positive histological changes of pancreatic islets and increase in the number of insulin-positive cells in the islets which was ac­companied by increased serum insulin level. These results show that 20HE administration to diabetic rats restrained islet destruc­tion and partially restored the number of insulin-positive cells. In addition, treatment of 20HE attenuated diabetes-induced liver damage in rats according to lower level of DNA damage and reduc­tion of oxidative damage oflipids. This result is in accordance with observed improvement of liver architecture in 20HE treated dia­betic rats. Staining of collagen and increase in E-cadherin and de­creases in a-smooth muscle actin revealed that administration of 20HE to diabetic rats attenuated fibrotic process in the liver. Conclusions: 20HE administration seems to be beneficial for improving the hyperglycemia by increasing beta-cell mass and preventing diabetic complications in liver by attenuating fibrotic process.