PROTECTIVE EFFECT OF ELLAGIC ACID AGAINST CYCLOSPORINE A-INDUCED RENAL HISTOPATHOLOGICAL AND ULTRASTRUCTURAL CHANGES, AND OXIDATIVE STRESS IN MALE ALBINO RATS

Abstract

Cyclosporine A (CsA) is an effective immunosuppressor agent, which is used in preventing graft rejection and in treating autoimmune diseases. The present study aimed to investigate the protective effect of ellagic acid (EA) against CsA-induced renal toxicity in male albino rats. Animals were divided into six groups, each of seven rats: the 1st group was used as a control, the 2nd group received a subcutaneous injection of slightly alkaline solution, the 3rd group received orally olive oil, the 4th group was injected subcutaneously with EA (10 mg/kg body weight, dissolved in slightly alkaline solution), the 5th group was orally treated with CsA (15 mg/kg body weight, dissolved in olive oil), and the 6th group was treated simultaneously with CsA and EA, daily for 30 days. The results indicated that CsA induced a significant increase in renal lipid peroxidation and a significant decrease in renal catalase and peroxidase activities, and reduced glutathione concentration. Histopathological changes of the renal cortex region of CsA-administrated rats revealed vacuolated cytoplasm of the epithelial cells and fibrosis, while the renal medullary region showed tubular calcification or casts, and damaged collecting tubules. Ultrastructural changes included marked degeneration of glomeruli, multiple cytoplasmic vacuoles of the cuboidal epithelial cells, thickened basal lamina, and sparse short microvilli of the proximal tubules. Treatment with EA simultaneously with CsA resulted in a significant alleviation of the renal histopathological and ultrastructural changes, and oxidative stress. Thus, it is recommended to use EA to alleviate CsA-induced renal toxicity due to its antioxidant effects.