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Protective Effects of Vinpocetine on Methotrexate-Induced Hepatic Oxidative Stress in Rats
Onural Ozhan1, Mucahit Baharcicek2, Mehmet Ediz Sarihan3, Azibe Yildiz4, Alaadin Polat5, Nigar Vardi4, Hakan Parlakpinar11Department of Medical Pharmacology, Faculty of Medicine, Inonu University, Malatya, Türkiye2Inonu University, Faculty of Medicine, Malatya, Türkiye
3Department of Emergency Medicine, Faculty of Medicine, Inonu University, Malatya, Türkiye
4Department of Histology and Embryology, Faculty of Medicine, Inonu University, Malatya, Türkiye
5Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Türkiye
Objectives: Methotrexate (MTX) is a potent antineoplastic and immunosuppressive drug; nevertheless, its therapeutic use is limited by hepatotoxicity, mostly driven by oxidative stress (OS). This research sought to examine the possible preventive impact of vinpocetine (VPC) against MTX-induced liver injury in rats.
Methods: Thirty-two female Wistar albino rats were randomly allocated into four groups: Control, MTX (20 mg/kg, single dose, intraperitoneally), VPC (10 mg/kg/day, intraperitoneally for 7 days), and MTX+VPC. Upon conclusion of the experiment, liver tissues and serum samples were obtained. Hepatic OS indicators, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), were assessed. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed. Histopathological evaluation focused on sinusoidal dilation and congestion.
Results: The treatment of MTX markedly elevated liver levels of MDA, TOS, and OSI, while concurrently diminishing SOD, CAT, GPx, and TAS values, signifying substantial OS. VPC co-administration markedly reduced MTX-induced oxidative imbalance, as shown by decreased MDA and OSI levels and a partial recovery of antioxidant enzyme activity. Serum AST and ALT levels exhibited no significant differences among the groups. Histopathological examination revealed that MTX caused considerable sinusoidal dilatation, which was somewhat reduced by VPC, but this reduction did not achieve statistical significance.
Conclusion: VPC offers partial protection against MTX-induced hepatic OS and early histopathological changes without influencing serum transaminase levels. These data indicate that VPC may function as a possible supplementary treatment to alleviate MTX-induced hepatotoxicity.
Keywords: Methotrexate, vinpocetine, hepatotoxicity, oxidative stress, rat model
Manuscript Language: English