title: Effect of proanthocyanidin, arginine and glutamine supplementation on methotrexate-induced gastrointestinal toxicity in rats.
abstract: Methotrexate is a folate antagonist that is commonly used as an antitumor and antiarthritic drug. The aim of this study was to investigate the possible roles of exogenous glutamine (Glu), arginine (Arg) and proanthocyanidin (PA) on gut protection from methotrexate-induced intestinal damage in rats. Experimental rats were separated into eight groups. The first (sham) group received a 0.9% NaCl solution alone. The second group received intraperitoneal injections of methotrexate (20 mg/kg/day) administered on day 4 of the experiment and continued for 5 days. Rats in the other six groups were administered PA, Glu, Arg, Glu+PA, Arg+PA or Glu+Arg orally by gavage together with methotrexate and animals were sacrificed on day 8 of the experiment. All animals were sacrificed 4 days after methotrexate injection for histopathological analysis, tissue glutathione peroxidase, malondialdehyde and superoxide dismutase assays. Proanthocyanidin and Glu decreased the severity of intestinal injury and oxidant injury as evident by histopathology and changes in malondialdehyde levels. Histological analysis confirmed that PA and to a lesser extent Glu supplementation were more favorable than Arg for the protection of the small intestine from methotrexate-induced injury.
authors.affiliation: Kayseri Military Hospital, Department of Pediatrics, Kayseri, Turkey. karaoglubaki@gmail.com
authors.forename: M
authors.initials: M
authors.lastname: Gulgun
authors.forename: A
authors.initials: A
authors.lastname: Karaoglu
authors.forename: V
authors.initials: V
authors.lastname: Kesik
authors.forename: B
authors.initials: B
authors.lastname: Kurt
authors.forename: O
authors.initials: O
authors.lastname: Erdem
authors.forename: D
authors.initials: D
authors.lastname: Tok
authors.forename: E
authors.initials: E
authors.lastname: Kismet
authors.forename: V
authors.initials: V
authors.lastname: Koseoglu
authors.forename: O
authors.initials: O
authors.lastname: Ozcan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005973:Glutamine / Q000008:administration & dosage / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007410:Intestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008727:Methotrexate / Q000633:toxicity*; D044945:Proanthocyanidins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D000975:Antioxidants; D044945:Proanthocyanidins; D005973:Glutamine; C013221:proanthocyanidin; D008315:Malondialdehyde; D001120:Arginine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D008727:Methotrexate