Nicotinamide Riboside Attenuates Hepatic Injury in a DHEA-Induced Polycystic Ovary Syndrome Rat Model: Potential Role of SIRT1 Expression

Abstract

Objective: This investigation aimed to explore the effects of nicotinamide riboside (NR) on liver injury in an experimental model of polycystic ovary syndrome (PCOS). Methods: The PCOS model was established according to Franks’ method. Rats were divided into three groups, randomly: control animals, PCOS animals, and PCOS + NR animals. NR was orally administered at a dose of 200 mg/kg once daily for seven days. Liver tissues were processed for histopathological and immunohistochemical examinations. Hematoxylin-eosin and Masson’s trichrome staining were performed for the assessment of general histoarchitecture and fibrosis, respectively. Sirtuin 1 (SIRT1) expression and localization were analyzed by immunofluorescence microscopy. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels were measured to evaluate liver function. Results: DHEA-induced PCOS rats exhibited significant weight gain and marked hepatic alterations, including microvesicular steatosis, hepatocyte ballooning, early perisinusoidal fibrosis, and elevated serum AST, ALT, and ALP levels (p < 0.01). NR treatment effectively attenuated weight gain, improved hepatic histopathology, reduced collagen deposition, and normalized liver enzyme levels (p < 0.01). Additionally, NR enhanced hepatic SIRT1 expression, suggesting improved mitochondrial function and reduced oxidative stress. Discussion: NR ameliorated PCOS-associated hepatic dysfunction, likely through SIRT1-mediated regulation of lipid metabolism and oxidative balance. These results suggest that NR may be a potential therapeutic agent for metabolic and hepatic complications associated with PCOS.