Journal article
Intervention of alpha-lipoic acid ameliorates methotrexate-induced oxidative stress and genotoxicity: A study in rat intestine
Chemico-biological interactions, Vol.183(1), pp.85-97
01/05/2010
DOI: 10.1016/j.cbi.2009.10.020
PMID: 19900424
Abstract
Methotrexate (MTX) is an anti-metabolite, widely used in the cancer chemotherapy and rheumatoid arthritis. However, its long-term clinical use is restricted on account of its severe intestinal toxicity. The present study was aimed to investigate the intestinal toxicity of MTX and the possible protective effect of a-lipoic acid (LA) on Sprague-Dawley rats. MTX-induced intestinal toxicity was evaluated at the dose of 2.5 mg/kg for short-term (5 days treatment) and 1 mg/kg for long-term (5 days in a week for four consecutive weeks treatment) study. The possible protective effect of LA was evaluated in both short- as well as long-term study in a dose-dependent manner. MTX treatment induced diarrhoea and mortality in rats, indicating its severe toxicity in the target organ of investigation, i.e., intestine. Further. the intestinal toxicity of MTX was assessed by evaluating different parameters of oxidative stress, DNA damage, cytotoxicity as well as histological changes. Immunostaining for p53 revealed higher genotoxic assault in the intestinal cells due to MTX treatment. Pretreatment of rats with LA led to significant decrease in the oxidative stress, DNA damage, cellular damage, inflammatory changes and apoptosis as determined by malondialdehyde level, glutathione level, comet assay parameters, histological evaluation, immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. In the present investigation, we report that LA pretreatment ameliorates MTX-induced intestinal toxicity in rat as evident from the protection against oxidative stress, decrease in DNA damage and protection of cellular morphology as well as improvement in the stool consistency and animal survival rate. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
Details
- Title: Subtitle
- Intervention of alpha-lipoic acid ameliorates methotrexate-induced oxidative stress and genotoxicity: A study in rat intestine
- Creators
- V. P. Dadhania - Johnson & JohnsonD. N. Tripathi - National Institute of Pharmaceutical Education and ResearchA. Vikram - National Institute of Pharmaceutical Education and ResearchP. Ramarao - National Institute of Pharmaceutical Education and ResearchG. B. Jena - National Institute of Pharmaceutical Education and Research
- Resource Type
- Journal article
- Publication Details
- Chemico-biological interactions, Vol.183(1), pp.85-97
- Publisher
- Elsevier
- DOI
- 10.1016/j.cbi.2009.10.020
- PMID
- 19900424
- ISSN
- 0009-2797
- eISSN
- 1872-7786
- Number of pages
- 13
- Grant note
- National Institute of Pharmaceutical Education and Research (NIPER)
- Language
- English
- Date published
- 01/05/2010
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984359888402771
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