Preclinical Efficacy of Melatonin to Reduce Methotrexate-Induced Oxidative Stress and Small Intestinal Damage in Rats

Background Methotrexate is widely used as a chemotherapeutic agent for leukemia and other malignancies. The efficacy of this drug is often limited by mucositis and intestinal injury, which are the major causes of morbidity in children and adults. Aim The present study investigates whether melatonin,...

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Bibliographic Details
Published in:Digestive diseases and sciences 2013-04, Vol.58 (4), p.959-969
Main Authors: Kolli, Viswa Kalyan, Abraham, Premila, Isaac, Bina, Kasthuri, N.
Format: Article
Language:English
Subjects:
Animals
Antimetabolites, Antineoplastic - adverse effects
Antioxidants - pharmacology
Antioxidants - therapeutic use
Biochemistry
Body weight
Cancer
Chemotherapy
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Drug therapy
Gastroenterology
Hepatology
Intestine, Small - drug effects
Intestine, Small - enzymology
Intestine, Small - pathology
Leukemia
Male
Medicine
Medicine & Public Health
Melatonin
Melatonin - blood
Melatonin - pharmacology
Melatonin - therapeutic use
Methotrexate
Methotrexate - adverse effects
Mucositis - chemically induced
Mucositis - prevention & control
Oncology
Original Article
Oxidative stress
Oxidative Stress - drug effects
Rats
Rats, Wistar
Superoxide
Transplant Surgery
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Summary:Background Methotrexate is widely used as a chemotherapeutic agent for leukemia and other malignancies. The efficacy of this drug is often limited by mucositis and intestinal injury, which are the major causes of morbidity in children and adults. Aim The present study investigates whether melatonin, a powerful antioxidant, could have a protective effect. Method Rats were pretreated with melatonin (20 and 40 mg/kg body weight) daily 1 h before methotrexate (7 mg/kg body weight) administration for three consecutive days. After the final dose of methotrexate, the rats were sacrificed and the small intestine was used for light microscopy and biochemical assays. Intestinal homogenates were used for assay of oxidative stress parameters malondialdehyde and protein carbonyl content, and myeloperoxidase activity, a marker of neutrophil infiltration as well as for the activities of the antioxidant enzymes. Result Pretreatment with melatonin had a dose-dependent protective effect on methotrexate (MTX)-induced alterations in small intestinal morphology. Morphology was saved to some extent with 20 mg melatonin pretreatment and near normal morphology was achieved with 40 mg melatonin pretreatment. Biochemically, pretreatment with melatonin significantly attenuated MTX-induced oxidative stress ( P  
ISSN:0163-2116
1573-2568
DOI:10.1007/s10620-012-2437-4