title: Chronic exposure to subtoxic levels of peroxidized lipids suppresses mucosal cell turnover in rat small intestine and reversal by glutathione.
abstract: Oxidative challenge can compromise intestinal growth and death responses. This studyexamines the effect of chronic consumption of subtoxic levels of peroxidized lipids on intestinal redox balance and turnover and the effect of glutathione (GSH) supplementation. Male Sprague-Dawley rats were fed standard rat chow or 4% peroxidized menhaden oil chow (2-8 weeks). Intestinal GSH and glutathione disulfide (GSSG), GSH synthetic and redox enzymes as well as proliferative (ornithine decarboxylase, ODC) and apoptotic activities were evaluated. Chronic peroxide intake did not affect overall animal growth, but decreased intestinal GSH/GSSG ratio that directly correlated with decreased GSH and increased GSSG, and suppressed peak circadian ODC activities and post-prandial mucosal apoptosis. Supplementation with GSH restored the mucosal GSH/GSSG ratio and abrogated the peroxide-induced suppression of intestinal cell turnover. Collectively, the results show that chronic lipid peroxide consumption induces intestinal GSH redox imbalance that interferes with regulation of enterocyte death and proliferation in vivo. These disruptive effects of lipid peroxides were reversed by GSH supplementation in accordance with the normalization of tissue GSH/GSSG redox balance.
authors.affiliation: Department of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, Louisiana 71130, USA.
authors.forename: Seiji
authors.initials: S
authors.lastname: Tsunada
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Iwakiri
authors.forename: Takahiro
authors.initials: T
authors.lastname: Noda
authors.forename: Kazuma
authors.initials: K
authors.lastname: Fujimoto
authors.forename: John
authors.initials: J
authors.lastname: Fuseler
authors.forename: Carol A
authors.initials: CA
authors.lastname: Rhoads
authors.forename: Tak Yee
authors.initials: TY
authors.lastname: Aw
mesh_terms: D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D005395:Fish Oils / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism*; D008054:Lipid Peroxides / Q000494:pharmacology*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005395:Fish Oils; D008054:Lipid Peroxides; C033266:Menhaden oil; D005978:Glutathione