Comparison between the ameliorative potentials of canagliflozin and metformin on the testicular damage in diabetic rats

Abstract

The current study aimed to evaluate the ameliorative effects of canagliflozin and metformin (MF) on the histological and ultrastructural alterations induced in testes of diabeticrats. Forty adult male Wistar rats were randomly divided into four groups: control group, diabetic group, metformintreated diabetic group, and canagliflozin-treated diabetic group. After thirty days of successive oral intubation, animals of all groups were dissected, and their testes were taken and processed for histological and ultrastructural examinations. In metformin-trated diabetic rats, the histopathological alterations were represented by degeneration of germ cells, and occurrence of large vacuoles in the germinal epithelia of some affected seminiferous tubules. The most prominent changes were represented by the congestion of blood vessels, as well as haemorrhage in the interstitial tissue. Ultrastructurally, the cytoplasm of the affected spermatogenic cells exhibited large numbers of degenerated mitochondria and fragmented rough endoplasmic reticulum. Sertoli cells exhibited highly folded and indented nuclear envelopes. In addition, necrotic Leydig cells were frequently observed. Histological and ultrastructural results revealed that treatment of diabetic male rats with canagliflozin may led to apparent improvement of the injured spermatogenic cells. Ultrastructurally, most of spermatogenic cells restored most of their normal cytoplasmic organelles, including the mitochondria which appeared almost intact. Conclusion: The present study suggests that, canagliflozin may act as a powerful agent, most likely by minimizing the diabetesinduced degenerations and derangements in the testicular tissue of diabetic rats.