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Melatonin and Melatonergic Drugs in Clinical Practice pp 389–402Cite as

Protective Effects of Exogenous Melatonin Against Methotrexate-Induced Intestinal Injury

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Abstract

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. We investigated whether melatonin, a powerful antioxidant, could have a protective effect. The rats were pretreated with melatonin (20 and 40 mg/kg body weight) daily 1 h before the MTX (7 mg/kg body weight) administration for three consecutive days. After the final dose of MTX, 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. Pretreatment with melatonin had a dose-dependent protective effect on 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 and restored the activities of the antioxidant enzymes. The results of the present study demonstrate that supplementation by exogenous melatonin significantly reduces MTX-induced small intestinal damage, indicating that it may be beneficial in ameliorating MTX-induced enteritis in humans.

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Acknowledgements

The authors acknowledge the Council for Scientific and Industrial Research (CSIR), New Delhi, for the financial support for the study and Mr. Viswa Kalyan Kolli, research fellow, for carrying out the biochemical studies.

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Authors and Affiliations

  1. Department of Biochemistry, Christian Medical College and Hospital, CMC College Campus, Bagayam, Vellore, TN, 632002, India

    Premila Abraham PhD

  2. Department of Anatomy, Christian Medical College and Hospital, CMC College Campus, Bagayam, Vellore, TN, 632002, India

    Bina Isaac MS

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  1. Premila Abraham PhD
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  2. Bina Isaac MS
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Correspondence to Premila Abraham PhD .

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Editors and Affiliations

  1. Sri Sathya Sai Medical Educational and Research Foundation, An International Medical Sciences Research Center, Coimbatore, Tamil Nadu, India

    V. Srinivasan

  2. Department of Obstetrics and Gynecology, Hadassah Hebrew-University Medical Center, Jerusalem, Israel

    Amnon Brzezinski

  3. Department of Physiology, Gulhane Military Medical Academy, Ankara, Turkey

    Sukru Oter

  4. Department of Psychiatry Behavioral Sciences, Mercer University School of Medicine, Macon, Georgia, USA

    Samuel D. Shillcutt

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Abraham, P., Isaac, B. (2014). Protective Effects of Exogenous Melatonin Against Methotrexate-Induced Intestinal Injury. In: Srinivasan, V., Brzezinski, A., Oter, S., Shillcutt, S. (eds) Melatonin and Melatonergic Drugs in Clinical Practice. Springer, New Delhi. https://doi.org/10.1007/978-81-322-0825-9_29

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  • DOI: https://doi.org/10.1007/978-81-322-0825-9_29

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