Protective role of hesperidin in finasteride-induced testicular toxicity in adult male Wistar rats: Insights into oxidative stress, apoptosis, and ultrastructure of seminiferous tubules.

A negative impact of finasteride on fertility has been reported, in which over production of reactive oxygen species and apoptosis were implicated. Hesperidin, a plant-derived bioflavonoid with antioxidant and anti-apoptotic effects, may mitigate these adverse effects. In order to investigate the possible protective role of hesperidin against finasteride-induced seminiferous tubules toxicity in adult male Wistar rats, 60 rats were randomized into five groups (I-V) receiving distilled water, 0.5% sodium carboxymethylcellulose solution, hesperidin, finasteride, and combined hesperidin and finasteride respectively. Testicular weight, sperm count and motility were determined. Testicular tissue homogenates were prepared to measure the level of malondialdehyde (MDA), total antioxidant capacity (TAC), reduced glutathione (GSH) and the gene expression of caspase-3 and B-cell lymphoma 2 (Bcl2). Testes were processed for light and electron microscopic evaluation. Johnsen score was calculated. Administration of finasteride resulted in significantly decreased testicular weights, sperm count and motility, Johnsen score, tissue levels of TAC and GSH together with significant increase in tissue MDA. Gene expression revealed significantly increased caspase-3 and decreased Bcl2. Furthermore, finasteride disrupted the seminiferous tubules, causing degenerative changes affecting Sertoli cells and spermatogenic cells. Co-administration of hesperidin with finasteride resulted in improvement in testicular weights, TAC, GSH, Bcl2, Johnsen score, sperm count and motility as well as preservation of the structure of the seminiferous tubules. To conclude, hesperidin was found to have a protective potential on finasteride-induced oxidative stress, apoptosis and testicular structural damage.

Possible protective effect of zinc administration on renal and cognitive changes occurring in uninephrectomized adult male Wistar rats.

NEW FINDINGS: What is the central question of this study? Are renal changes occurring post-nephrectomy accompanied by cognitive changes, and does early administration of zinc supplements such as ZnSO4 to uninephrectomized rats ameliorate the renal and cognitive changes if present? What is the main finding and its importance? Uninephrectomy-induced renal changes were accompanied by species-atypical behaviour in rats in both Morris water maze and T maze tests, together with hypozincaemia and hippocampal inflammatory and oxidative changes. Early zinc administration to uninephrectomized rats ameliorated the renal, behavioural, hippocampal and serum zinc changes. ABSTRACT: Cognitive impairment is increasingly recognized as an important consequence of kidney disease in humans. Kidney donation is a safe procedure but is known to increase the long-term risk of cardiovascular and kidney disease. Whether kidney donation impairs cognitive function is not known. In the present study, we examined whether the renal changes occurring post-nephrectomy were accompanied by cognitive changes as well, and whether early administration of zinc supplements such as ZnSO4 to uninephrectomized (UNX) rats could ameliorate the renal and cognitive changes if present. The present study included 30 adult male Wistar rats that were randomly assigned to three groups (n = 10 per group): sham-operated rats, UNX and UNX treated with ZnSO4 for 20 weeks. Before termination, rats were subjected to 24-h urine collection and behavioural testing with the Morris water maze and T maze tests. UNX induced significant proteinuria, renal functional, fibrotic and oxidative changes, as well as increased renal desmin expression. UNX rats also showed significant behavioural changes indicating spatial learning and memory affection, together with decreased hippocampal brain derived neurotrophic factor (BDNF) and antioxidant capacity, and increased glial fibrillary acidic protein (GFAP), nitric oxide and malondialdehyde. In addition, UNX induced significant hyperglycaemia and dyslipidaemia, as well as significant reduction in serum zinc, copper and selenium. Early administration of ZnSO4 starting 1 week post-nephrectomy significantly ameliorated renal and behavioural changes, as well as hippocampal oxidative, BDNF and GFAP changes. Additionally, Zn recovered serum changes of triglycerides, cholesterol, zinc and copper. Therefore, early administration of zinc to humans undergoing nephrectomy may be of benefit and should be considered in human trials.