Protective effect of dietary supplementation with L-arginine and L-carnitine on hypoxia/reoxygenation-induced necrotizing enterocolitis in young mice.
Oxygen-derived free radicals are important components of gastrointestinal injury in necrotizing enterocolitis (NEC). In the present investigation, we examined the protective actions of L-arginine, a nitric oxide synthase substrate, and L-carnitine against hypoxia-reoxygenation (H/R) induced NEC in young mice. Young mice were divided into four groups: group 1 mice were subjected to H/R only; group 2 H/R mice were supplemented with L-arginine in the drinking water (2 g/l) for 7 days; group 3 H/R mice were given L-carnitine solution in water (50 mg/kg p.o.) for 7 days, and group 4 mice served as controls. Hypoxia was induced by placing the mice in a 100% CO(2) chamber for 5 min. After hypoxia, the mice were reoxygenated for 10 min with 100% oxygen. We examined the intestinal lesions by light microscopy and measured the intestinal generation of thiobarbituric acid reactive substances (TBARS) and the activities of superoxide dismutase and catalase in the H/R-induced model of NEC. In both L-arginine and L-carnitine groups, the NEC-induced intestinal tissue damage was greatly attenuated, with necrosis limited partially to the mucosa. The tissue TBARS level was significantly higher in group 1 than in any of the other groups (p < 0.001). However, those treated with L-arginine and L-carnitine had TBARS levels similar to those in the control animals. An increased tissue concentration of nitrate, a stable metabolite of nitric oxide, was found in the L-arginine-supplemented group as compared with the control group (p < 0.05). Both superoxide dismutase and catalase activities in the intestine were similar in H/R groups when compared with the intestine of control animals. The present study suggests that oxygen-derived free radicals are involved in the pathogenesis of H/R-induced NEC. This study also shows that dietary supplementation with L-arginine and L-carnitine ameliorates the histological evidence of H/R-induced intestinal injury and significantly decreases lipid peroxidation in H/R-induced bowel injury. Based on these findings, the beneficial effects of L-arginine and L-carnitine in this model may be mediated via mechanisms preventing free radical damage.
Akisu
Mete
M
Department of Pediatrics, Ege University Medical School, Izmir, Turkey. makisu@med.ege.edu.tr
Ozmen
Dilek
D
Baka
Meral
M
Habif
Sara
S
Yalaz
Mehmet
M
Arslanoglu
Sertac
S
Kultursay
Nilgun
N
Bayindir
Oya
O
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology*; D002331:Carnitine / Q000008:administration & dosage / Q000494:pharmacology*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000473:pathology*; D000860:Hypoxia / Q000503:physiopathology; D015227:Lipid Peroxidation; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017392:Thiobarbituric Acid Reactive Substances; D001120:Arginine; D002331:Carnitine