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
,
Rekha Kota
Abstract
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
These findings suggest that AG is beneficial in ameliorating MTX-induced enteritis in rats.
Acknowledgments
The authors acknowledge the Center for Scientific and Industrial Research (CSIR), New Delhi, for the financial support it has provided for the study (No. 37/(1358)/09/EMR-II). Ms. Kasthuri Natarajan worked as a senior research fellow on the project.
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.
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©2017 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Isolated heart models for studying cardiac electrophysiology: a historical perspective and recent advances
- Reproduction
- Sub-chronic indomethacin treatment and its effect on the male reproductive system of albino rats: possible protective role of black tea extract
- The effect of extracellular ATP on rat uterine contraction from different gestational stages and its possible mechanisms of action
- Cardiovascular Function
- Effect of cardiovascular and muscular endurance is not associated with stress fracture incidence in female military recruits: a 12-month follow up study
- Cardiovascular-Pulmonary Interactions
- Comparison of structured and unstructured physical activity training on predicted VO2max and heart rate variability in adolescents – a randomized control trial
- Oxidative Stress
- Aminoguanidine pretreatment prevents methotrexate-induced small intestinal injury in the rat by attenuating nitrosative stress and restoring the activities of vital mitochondrial enzymes
- Anti-aging effects of M2000 (β-D-mannuronic acid) as a novel immunosuppressive drug on the enzymatic and non-enzymatic oxidative stress parameters in an experimental model
- Metabolism
- Long-term exposure to a butter-rich diet induces mild-to-moderate steatosis in Chang liver cells and Swiss albino mice models
- Effect of adrenocorticotropic hormone on UCP1 gene expression in brown adipocytes
- Phytotherapy
- Antidiabetic effect of Ruta montana L. in streptozotocin-induced diabetic rats
- Ethnopharmacological investigation of the aerial part of Phragmites karka (Poaceae)
Articles in the same Issue
- Frontmatter
- Review
- Isolated heart models for studying cardiac electrophysiology: a historical perspective and recent advances
- Reproduction
- Sub-chronic indomethacin treatment and its effect on the male reproductive system of albino rats: possible protective role of black tea extract
- The effect of extracellular ATP on rat uterine contraction from different gestational stages and its possible mechanisms of action
- Cardiovascular Function
- Effect of cardiovascular and muscular endurance is not associated with stress fracture incidence in female military recruits: a 12-month follow up study
- Cardiovascular-Pulmonary Interactions
- Comparison of structured and unstructured physical activity training on predicted VO2max and heart rate variability in adolescents – a randomized control trial
- Oxidative Stress
- Aminoguanidine pretreatment prevents methotrexate-induced small intestinal injury in the rat by attenuating nitrosative stress and restoring the activities of vital mitochondrial enzymes
- Anti-aging effects of M2000 (β-D-mannuronic acid) as a novel immunosuppressive drug on the enzymatic and non-enzymatic oxidative stress parameters in an experimental model
- Metabolism
- Long-term exposure to a butter-rich diet induces mild-to-moderate steatosis in Chang liver cells and Swiss albino mice models
- Effect of adrenocorticotropic hormone on UCP1 gene expression in brown adipocytes
- Phytotherapy
- Antidiabetic effect of Ruta montana L. in streptozotocin-induced diabetic rats
- Ethnopharmacological investigation of the aerial part of Phragmites karka (Poaceae)
