Resveratrol protects against methotrexate-induced hepatic injury in rats.
OBJECTIVE
The aim of this study to investigate the possible protective effect of resveratrol on some liver and serum/plasma parameters in methotrexate induced toxicity in rats. Methotrexate is used widely to treat various neoplastic diseases such as acute lymphoblastic leukemia, lymphoma, solid cancers, and autoimmune diseases. We hypothesized that resveratrol has a potential to decrease the oxidant damage in MTX-induced hepatic injury.


METHODS
Following a single dose of methotrexate (20 mg/kg, i.p.), either saline or resveratrol (10 mg/kg, orally) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the liver was removed to measure malondialdehyde and glutathione levels, myeloperoxidase and thromboplastic activities and collagen content. Aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase activity were measured in the serum samples, while TNF-alpha and total antioxidant capacity were assayed in plasma samples.


RESULTS
Our results showed that MTX administration increased the hepatic malondialdehyde levels, myeloperoxidase and thromboplastic activities and collagen contents and decreased glutathione, while these alterations were reversed in resveratrol-treated group. Elevated aspartate aminotransferase and alanine aminotransferase activities and TNF-alpha level observed following MTX treatment was depressed with resveratrol.


CONCLUSIONS
The present study showed that resveratrol protects against methotrexate-induced hepatic injury and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics.
Tunali-Akbay
Tugba
T
Marmara University School of Dentistry, Department of Biochemistry, Istanbul, Turkey. ttunali@marmara.edu.tr
Sehirli
Ozer
O
Ercan
Feriha
F
Sener
Goksel
G
D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000517:prevention & control; D005260:Female; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077185:Resveratrol; D008727:Methotrexate