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Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation.
Hum Exp Toxicol. 2013 Jun; 32(6):662-71.HE

Abstract

Hepatotoxicity is one of the major complications of methotrexate (MTX) therapy. This study was carried out to evaluate the possible protective effect of resveratrol (trans-3,5,4'-trihydroxystilbene, RVT) against MTX-induced hepatotoxicity. Rats were randomly divided into four groups as control, MTX treated (7 mg/kg/day, intraperitoneally (i.p.), once daily for 3 consecutive days), MTX + RVT treated (20 mg/kg/day, i.p.), and RVT treated. First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days. Histopathology of liver was evaluated by light microscopy. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. The levels of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and activities of hepatic antioxidant enzymes such as catalase (CAT) and glutathione-S-transferase (GST) were used to analyze the oxidative stress-mediated lipid peroxidation in liver sections. Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels. TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration. RVT treatment significantly prevented MTX-induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology. Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX-treated group. These results revealed that RVT may have a protective effect against MTX-induced hepatotoxicity by inhibiting oxidative stress-mediated lipid peroxidation. Consequently, RVT treatment might be a promising strategy against MTX-induced hepatotoxicity.

Authors+Show Affiliations

Department of Pharmacology, Medical Faculty, Akdeniz University, Antalya, Turkey. stasatargil@akdeniz.edu.trNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23424212

Citation

Dalaklioglu, S, et al. "Resveratrol Ameliorates Methotrexate-induced Hepatotoxicity in Rats Via Inhibition of Lipid Peroxidation." Human & Experimental Toxicology, vol. 32, no. 6, 2013, pp. 662-71.
Dalaklioglu S, Genc GE, Aksoy NH, et al. Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation. Hum Exp Toxicol. 2013;32(6):662-71.
Dalaklioglu, S., Genc, G. E., Aksoy, N. H., Akcit, F., & Gumuslu, S. (2013). Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation. Human & Experimental Toxicology, 32(6), 662-71. https://doi.org/10.1177/0960327112468178
Dalaklioglu S, et al. Resveratrol Ameliorates Methotrexate-induced Hepatotoxicity in Rats Via Inhibition of Lipid Peroxidation. Hum Exp Toxicol. 2013;32(6):662-71. PubMed PMID: 23424212.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation. AU - Dalaklioglu,S, AU - Genc,G E, AU - Aksoy,N H, AU - Akcit,F, AU - Gumuslu,S, Y1 - 2013/02/19/ PY - 2013/2/21/entrez PY - 2013/2/21/pubmed PY - 2013/12/24/medline KW - Resveratrol KW - hepatotoxicity KW - lipid peroxidation KW - methotrexate SP - 662 EP - 71 JF - Human & experimental toxicology JO - Hum Exp Toxicol VL - 32 IS - 6 N2 - Hepatotoxicity is one of the major complications of methotrexate (MTX) therapy. This study was carried out to evaluate the possible protective effect of resveratrol (trans-3,5,4'-trihydroxystilbene, RVT) against MTX-induced hepatotoxicity. Rats were randomly divided into four groups as control, MTX treated (7 mg/kg/day, intraperitoneally (i.p.), once daily for 3 consecutive days), MTX + RVT treated (20 mg/kg/day, i.p.), and RVT treated. First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days. Histopathology of liver was evaluated by light microscopy. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. The levels of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and activities of hepatic antioxidant enzymes such as catalase (CAT) and glutathione-S-transferase (GST) were used to analyze the oxidative stress-mediated lipid peroxidation in liver sections. Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels. TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration. RVT treatment significantly prevented MTX-induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology. Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX-treated group. These results revealed that RVT may have a protective effect against MTX-induced hepatotoxicity by inhibiting oxidative stress-mediated lipid peroxidation. Consequently, RVT treatment might be a promising strategy against MTX-induced hepatotoxicity. SN - 1477-0903 UR - https://www.unboundmedicine.com/medline/citation/23424212/Resveratrol_ameliorates_methotrexate_induced_hepatotoxicity_in_rats_via_inhibition_of_lipid_peroxidation_ L2 - https://journals.sagepub.com/doi/10.1177/0960327112468178?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -