Caffeic acid abrogates amyloidosis, hypospermatogenesis and cell membrane alterations in the testes and epididymis of fructose-diabetic rats by upregulating steroidogenesis, PCNA and Nrf2 expression.

The fructose-streptozotocin (FRU-STZ) diabetic model has been presented as a viable model of type2 diabetes but its impact on the testes and epididymis of Wistar rats is yet to be investigated. In this study, we probed the role of caffeic acid, a potent antioxidant, in FRU-STZ diabetic rats. Twenty normoglycemic rats were randomly divided into four groups of five rats each: Control, Fructose-Streptozotocin (FRU+STZ), Fructose-Streptozotocin + Caffeic Acid (FRU+STZ+CA), and Caffeic Acid (CA). Diabetes was induced by the administration of 10 % fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of 50 mg/kg bwt of streptozotocin. Treatment with CA (50 mg/kg bwt) lasted for two weeks. Results showed that FRU-STZ diabetes was able to induce amyloidosis and histopathological deficits in the testis and epididymis characteristic of cytotoxic agents. Poor PCNA immunoreactivity, reactive Nrf2 expression, and defective steroidogenesis were also observed in the diabetic group. FRU-STZ diabetes was also associated with significantly increased Na+-K+ ATPase activity in both testes and epididymis. Treatment with caffeic acid was able to restore steroidogenesis and spermatogenesis in the diabetic rats to levels comparable to the control; histological features and Na+-K+ ATPase activity were also reduced in the CA-treated group. Generally, normal rats treated with caffeic acid did not evince any deleterious effects. Our study demonstrates that CA exerts a protective role in FRU-STZ diabetes.