Resveratrol protects against letrozole-induced renal damage in a rat model of polycystic ovary syndrome: A biochemical, histological, and immunohistochemical study

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects 9-18 % of women, often associated with metabolic and renal complications. This study aimed to investigate the renoprotective effects of resveratrol (RSV) in a letrozole-induced rat model of PCOS, focusing on biochemical, histological, ultrastructural, and immunohistochemical alterations. METHODS: Thirty female rats were randomly divided into five groups: negative control, only RSV-treated, PCOS-induced (sham), metformin-treated, and RSV-treated. Serum testosterone, urea, and creatinine levels were assessed. Renal tissues underwent histological, immunohistochemical, ultrastructural, and morphometric analyses. Additionally, TGF-β1 mRNA expression was evaluated using qRT-PCR. RESULTS: Letrozole administration significantly elevated serum testosterone, urea, and creatinine levels, indicating PCOS-associated renal dysfunction. Histological and ultrastructural analysis revealed severe glomerular and tubular alterations in the sham group. The administration of RSV significantly restored renal architecture and function more effectively than metformin. Immunohistochemistry analysis showed that RSV reduced Proliferating Cell Nuclear Antigen (PCNA) overexpression and restored B-cell Lymphoma 2 (BCL-2) expression, suggesting a protective effect against cellular stress and apoptosis. Moreover, RSV significantly downregulated TGF-β1 expression, indicating its anti-fibrotic and anti-inflammatory role in PCOS-related renal damage. CONCLUSION: In a PCOS rat model, RSV protects effectively against letrozole-induced structural and functional renal damage. It demonstrates superior efficacy over metformin in restoring renal function, reducing apoptosis, and mitigating fibrosis. These findings suggest that RSV may serve as a potential adjunct therapy for preventing PCOS-associated renal complications, emphasizing the need for further investigations.