Protective effect of ellagic acid against cyclosporine A-induced histopathological, ultrastructural changes, oxidative stress, and cytogenotoxicity in albino rats

Abstract

Cyclosporine A (CsA) is an immunosuppressor agent, which is most frequently used in transplant surgeries and in the treatment of autoimmune diseases. This study was undertaken to investigate the protective effects of ellagic acid (EA) against CsA-induced testicular histopathology and ultrastructure changes, oxidative stress, and cytogenotoxicity in male albino rats. Rats were divided into six groups; the first group was used as a control, the second group received a subcutaneous injection of slightly alkaline solution, the third group received olive oil orally, the fourth group was injected subcutaneously with EA at a dose of 10 mg/kg b. wt./day, the fifth group was treated with CsA as oral solution at a dose of 15 mg/kg b. wt for 30 days, and the sixth group was treated with CsA simultaneously with EA. Treatment with EA simultaneously with CsA resulted in significant protection. The positive control animals taking CsA alone showed marked histopathological, ultrastructure, and genetic manifestations accompanied by an elevated content of lipid peroxidation and marked reduction of catalase (CAT), peroxidase (Px) activity, and glutathione concentration in the homogenate of testis tissues. The toxic side effects in testis and bone marrow tissues were greatly ablated with a significant reduction in lipid peroxidation level and elevation in CAT and Px activities and glutathione concentration when using EA. Thus, EA may be used in combination with CsA to improve the histopathological, oxidative stress, and cytogenotoxicity parameters of testicular toxicity induced by CsA due to its antioxidant effects.

Keywords: Cyclosporine A; chromosomal aberrations; ellagic acid; histopathology and ultrastructure; oxidative stress.