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Role of grape seed extract on methotrexate induced oxidative stress in rat liver
Aysun Cetin1, Leylagul Kaynar, Ismail Kocyigit
1Department of Biochemistry and Clinical Biochemistry, Erciyes University, Kayseri, Turkey. aysuncetin@yahoo.com
Unlabelled:
The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by its severe hepatotoxicity. Regarding the mechanisms of these adverse effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether grape seed extract (GSE), a new natural free radical scavenger, could ameliorate the MTX-induced oxidative injury in the rat liver. The animals were divided into 3 groups. Each group consisted of 12 animals. MTX-GSE group: rats were given GSE (100mg/kg body weight) orally for 15 days, and a single dose of MTX (20 mg/kg, intraperitoneally) was added on the 10th day. MTX group: these received placebo distilled water (orally) instead of GSE for 15 days and the same MTX protocol applied to this group on the 10th day.
Control Group:
rats were given distilled water (orally) through 15 days and physiological saline (intraperitoneally) instead of MTX was administered on the 10th day in a similar manner. On the 16th day, liver tissue samples were obtained under deep anaesthesia. The level of malondialdehyde (MDA), an end product of lipid peroxidation, and the activities of süperoxide dismutase (SOD) and catalase (CAT), two important endogenous antioxidants, were evaluated in the tissue homogenates. MTX administration increased the MDA level and decreased the SOD and CAT activities in the liver homogenates (p < 0.001), while these alterations were significantly reversed by GSE treatment (p < 0.001). MTX led to significantly reduced whole blood count parameters (p < 0.05). When GSE was supplemented, no significant changes in blood count parameters were noted. It appears that GSE protects the rat liver and inhibits methotrexate-induced oxidative stress. These data indicate that GSE may be of therapeutic benefit when used with MTX.
Insights
Grape seed extract (GSE) can protect the rat liver from methotrexate (MTX)-induced oxidative stress. GSE supplementation reversed MTX-induced liver damage and normalized blood counts, suggesting therapeutic potential.
Area of Science:
- Hepatology
- Pharmacology
- Toxicology
Background:
- Methotrexate (MTX) is a chemotherapy drug with significant hepatotoxicity.
- Oxidative stress is a suspected mechanism behind MTX-induced liver injury.
- Grape seed extract (GSE) is a natural antioxidant with potential protective properties.
Purpose of the Study:
- To investigate the protective effects of GSE against MTX-induced liver damage in rats.
- To determine if GSE can ameliorate MTX-induced oxidative stress in the liver.
Main Methods:
- Rats were divided into three groups: MTX-GSE, MTX, and control.
- Animals received either GSE or placebo orally for 15 days, with a single MTX dose administered on day 10.
- Liver tissue was analyzed for malondialdehyde (MDA) levels and superoxide dismutase (SOD) and catalase (CAT) activities.
Main Results:
- MTX administration significantly increased MDA levels and decreased SOD and CAT activities in the liver.
- GSE treatment significantly reversed these MTX-induced alterations.
- MTX reduced blood count parameters, but GSE supplementation prevented these changes.
Conclusions:
- GSE demonstrates protective effects on the rat liver against MTX-induced oxidative stress.
- GSE may be a beneficial therapeutic supplement when co-administered with MTX.
- Grape seed extract shows promise in mitigating chemotherapy-induced liver toxicity.
