A preclinical study on the protective effect of melatonin against methotrexate-induced small intestinal damage: effect mediated by attenuation of nitrosative stress, protein tyrosine nitration, and PARP activation
| Autor: | Kasthuri Natarajan, Viswa Kalyan Kolli, Bina Isaac, Hemalatha Ramamoorthy, Minnie Faith, Indirani Kanakasabapathy, Premila Abraham |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
musculoskeletal diseases Antimetabolites Antineoplastic Cancer Research Side effect Poly ADP ribose polymerase Pharmacology Toxicology Melatonin Intestine Small medicine Mucositis Animals Pharmacology (medical) Intestinal Mucosa Rats Wistar skin and connective tissue diseases Enterocolitis Nitrates Dose-Response Relationship Drug business.industry Tyrosine Nitration medicine.disease Small intestine Rats Oxidative Stress Methotrexate medicine.anatomical_structure Oncology Tyrosine Poly(ADP-ribose) Polymerases medicine.symptom business medicine.drug |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 71:1209-1218 |
| ISSN: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-013-2115-z |
| Popis: | One of the major toxic side effects of methotrexate (MTX) is enterocolitis. To date, there is no efficient standard treatment for this side effect. Nitrosative stress is reported to play a critical role in MTX-induced mucositis. The purpose of this study is to investigate whether pretreatment with melatonin, an inhibitor of nitro-oxidative stress, prevents MTX-induced mucositis in rats.Rats were pretreated with melatonin (20 and 40 mg/kg body weight) i.p. daily 1 h before MTX (7 mg/kg body weight) administration for three 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. The villi were distorted, blunted, and atrophied and focally absent in various segments of the small intestines. Crypt abscesses were also found, suggesting an inflammatory response. Pretreatment with melatonin had a dose-dependent protective effect on MTX-induced mucositis. Morphology was saved to a moderate extent with 20 mg melatonin pretreatment, and near-normal morphology was achieved with 40 mg melatonin pretreatment. Damage to the villi and crypt abscess was reduced. The villi/crypt ratio was almost restored. Melatonin pretreatment protected the small intestines from MTX-induced damage by attenuating nitrosative stress, protein tyrosine nitration and PARP expression.Because of its versatility in protecting against nitro-oxidative stress and reducing inflammation, we suggest that melatonin could be beneficial in ameliorating MTX-induced enteritis in humans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink