Oxidative Stress in Fatty Livers of Obese Zucker Rats: Rapid Amelioration and Improved Tolerance to Warm Ischemia With Tocopherol

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Abstract
Fatty livers in humans and rats are less tolerant of ischemia, endotoxin, and alcohol. We hypothesized that fatty livers of obese (Ob) Zucker rats are oxidatively stressed and oxidative stress could be relieved by antioxidant treatment, leading to improved tolerance to ischemia. Total glutathione (GSH), tocopherol (TOC), ascorbic acid (AA), catalase (CAT), superoxide dismutase (SOD), and selenium-glutathione peroxidase (Se–GPx) were measured in the livers of Ob and lean (Ln) Zucker rats before and after treatment with high–dose TOC and ascorbate. Also, survival in treated Ob rats following a lethal 90 minutes of partial in vivo warm ischemia was examined. Fatty livers of Ob rats contained significantly less GSH, TOC, and CAT, in comparison with livers of Ln rats. Immunoblotting showed significantly decreased CAT protein without changes in mRNA in fatty livers. There were no significant differences in AA, SOD, and Se–GPx between the 2 groups. Pretreatment with TOC and ascorbate over 48 hours completely corrected the decreases in GSH, TOC, and CAT. Most importantly, TOC with or without ascorbate pretreatment significantly improved survival in Ob rats following ischemia in a dose–dependent manner. In conclusion, TOC administration corrected the oxidative stress in fatty livers of Ob Zucker rats and improved survival following lethal ischemia. Additional studies are needed to determine the efficacy of TOC—a relatively inexpensive agent—in treating patients with fatty livers in a variety of clinical conditions, possibly including liver transplantation.

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