HEPATOPROTECTIVE ROLE OF NICOTINAMIDE MONONUCLEOTIDE IN PCOS: HISTOPATHOLOGICAL AND BIOCHEMICAL EVIDENCE FROM A RAT MODEL

Objective: The objective of this study was to investigate the histopathological and biochemical effects of nicotinamide mononucleotide (NMN) on polycystic ovary syndrome (PCOS)-associated liver injury in a rat model. Methods: PCOS was experimentally induced in rats, after which the animals were randomly assigned to three groups: control, PCOS, and PCOS treated with NMN. NMN was administered intraperitoneally at a dose of 500 mg/kg/day for seventeen consecutive days. Liver tissues were collected for histological analyses. General hepatic architecture and fibrotic alterations were evaluated using hematoxylin–eosin and Masson’s trichrome staining, respectively. Enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were measured as indicators of liver function. Results: Histopathological analysis demonstrated significant hepatic damage in the PCOS group, including hepatocellular ballooning, steatosis, spotty necrosis, portal and lobular inflammation, sinusoidal dilatation, increased apoptotic hepatocytes, and enhanced collagen deposition. Semi-quantitative scoring revealed significantly higher portal inflammation, ballooning degeneration, steatosis, spotty necrosis, and capsular inflammation scores in the PCOS group compared with controls. NMN treatment markedly ameliorated these histopathological alterations, as evidenced by reduced histopathological damage. Accordingly, semi-quantitative histopathological scores were significantly lower in the PCOS+NMN group than in the PCOS group. Consistent with histological findings, serum AST, ALT, and ALP activities were significantly elevated in the PCOS group but were significantly reduced following NMN administration, indicating an improvement in PCOS-associated hepatic injury. Also, NMN significantly attenuated PCOS-associated body weight gain. Conclusion: NMN treatment markedly alleviated PCOS-associated liver injury by improving hepatic histopathology and normalizing liver enzyme activities