Novel protective effect of diosmin against cisplatin-induced prostate and seminal vesicle damage: Role of oxidative stress and apoptosis

Abstract

Multiple organ toxicity has been associated with cisplatin (CIS) treatment, limiting its clinical use. The human prostate and seminal vesicles are accessory sex organs with androgen-dependent morphogenesis, growth, and secretion. The present study aimed to investigate, for the first time, the toxic effect of CIS on normal prostate and seminal vesicles in the presence and absence of diosmin (DS). The animals were randomized into 4 groups as follows: control (received vehicle), CIS group (7.5 mg/kg, i.p. on 5th and 12th day), DS group (100 mg/kg, p.o. for 15 days), and DS+CIS group. Histopathological and biochemical analyses were conducted to elucidate the goal of this study. CIS administration significantly induced prostate and seminal vesicle toxicity as evidenced by alteration of serum testosterone, LH, FSH, PSA, steroidogenic HSD17B6 as well as seminal analysis markers. Remarkably, marked histopathological changes in thin and ultrathin structures were observed. Besides, CIS significantly boosted oxidative stress as evidenced by the up-regulation of MDA and down-regulation of TAC. CIS significantly induced tissue apoptosis concomitant with suppression of cellular proliferation and stem cell expression as indicated by up-regulation of activated caspase-3 and Bax expression along with down-regulation of Bcl-2, Ki67, and CD44 expression. Interestingly, DS fixed all disturbances in the prostate and seminal vesicles induced by CIS. Together, CIS could cause prostate and seminal vesicle toxicity by affecting hormonal, steroidogenic, oxidative stress, apoptosis, and proliferation processes, and this effect was reversed by DS administration.