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Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph

CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

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Volume 28, Issue 3


Aminoguanidine pretreatment prevents methotrexate-induced small intestinal injury in the rat by attenuating nitrosative stress and restoring the activities of vital mitochondrial enzymes

Kasthuri Natarajan / Premila Abraham
  • Corresponding author
  • Department of Biochemistry, Christian Medical College, Bagayam, Vellore 632002, Tamil Nadu, India, Phone: +914162284267, Mobile: +919894746285, Fax: +91-416-2262788
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/ Rekha Kota / Dhayakani Selvakumar
Published Online: 2017-01-18 | DOI: https://doi.org/10.1515/jbcpp-2016-0099



One of the major toxic side effects of methotrexate (MTX) is enterocolitis, for which there is no efficient standard treatment. Nitric oxide overproduction has been reported to play an important role in MTX-induced mucositis. This study was designed to investigate whether pretreatment with aminoguanidine (AG) – a selective iNOS inhibitor – prevents MTX-induced mucositis in rats.


Rats were pretreated with AG (30 and 50 mg/kg body weight) i.p. daily 1 h before MTX (7 mg/kg body weight) administration for 3 consecutive days. After the final dose of MTX, the rats were killed, and the small intestines were used for analysis.


The small intestines of MTX-treated rats showed moderate to severe injury. Pretreatment with AG had a dose-dependent protective effect on MTX-induced mucositis. AG pretreatment reduced iNOS protein levels, mucosal nitric oxide levels, and protein tyrosine nitration. AG pretreatment also restored the activities of electron transport chain (ETC) complexes, vital tricarboxylic acid (TCA cycle) enzymes, and mitochondrial antioxidant enzymes.


These findings suggest that AG is beneficial in ameliorating MTX-induced enteritis in rats.

Keywords: aminoguanidine; antioxidant enzymes; ETC activity; methotrexate; nitrosative stress; small intestinal injury; TCA cycle enzymes


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About the article

Received: 2016-06-29

Accepted: 2016-10-26

Published Online: 2017-01-18

Published in Print: 2017-05-01

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: Center for scientific and Industrial research (CSIR) (No. 37/(1358)/09/EMR-II).

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 28, Issue 3, Pages 239–247, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2016-0099.

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