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Chronic Exposure to Subtoxic Levels of Peroxidized Lipids Suppresses Mucosal Cell Turnover in Rat Small Intestine and Reversal by Glutathione

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Abstract

Oxidative challenge can compromise intestinal growth and death responses. This study examines 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 postprandial 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.

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Authors and Affiliations

  1. Department of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center, Louisiana, 71130, USA

    Seiji Tsunada, Carol A. Rhoads & Tak Yee Aw

  2. Department of Internal Medicine, Saga Medical School, Saga, Japan

    Ryuichi Iwakiri, Takahiro Noda & Kazuma Fujimoto

  3. Department of Medicine, Louisiana State University Health Sciences Center, Louisiana, 71130, USA

    John Fuseler

Authors
  1. Seiji Tsunada
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  2. Ryuichi Iwakiri
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  3. Takahiro Noda
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  4. Kazuma Fujimoto
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  5. John Fuseler
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  6. Carol A. Rhoads
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  7. Tak Yee Aw
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Tsunada, S., Iwakiri, R., Noda, T. et al. Chronic Exposure to Subtoxic Levels of Peroxidized Lipids Suppresses Mucosal Cell Turnover in Rat Small Intestine and Reversal by Glutathione. Dig Dis Sci 48, 210–222 (2003). https://doi.org/10.1023/A:1021775524062

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