The Tohoku Journal of Experimental Medicine
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One-Day Dietary Restriction Changes Hepatic Metabolism and Potentiates the Hepatotoxicity of Carbon Tetrachloride and Chloroform in Rats
Li-Qiang QinYuan WangJia-Ying XuTakashi KanekoAkio SatoPei-Yu Wang
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Volume 212 (2007) Issue 4 Pages 379-387

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Abstract

Although dietary restriction (DR) is common in modern society, research about hepatic metabolism and the hepatotoxicity induced by DR has been conducted less intensively than that induced by fasting. In the present study, we fed male Wistar rats at five levels of food intake for one day, including conventional feeding (60 kcal), three of DR (45, 30, and 15 kcal), and fasting (0 kcal), and observed the metabolic changes of hepatic cytochrome P450 2E1(CYP2E1) and the hepatotoxicity of chloroform (CHCl3) and carbon tetrachloride (CCl4). The CYP2E1 content was significantly increased in 15 kcal-food and fasting groups. The hepatic glutathione (GSH) content, which protects the liver from hepatotoxic agents, was depleted in 15 kcal-food and fasting groups. After the challenge by CHCl3 and CCl4, the activities of aspartate aminotransferase and alanine aminotransferase, marker enzymes for liver damage, were elevated remarkably at all food groups. Moreover, their activities increased significantly in DR groups, in comparison to the corresponding 60 kcal-food group. After the challenge, the hepatic GSH content was also depleted significantly in 15 kcal-food and fasting groups. CHCl3 was cleared by hepatic metabolism about 8-10 times faster than that of CCl4. Similarly, the areas under the blood concentration-time curve of CCl4 was as much as twice that of the corresponding CHCl3. In conclusion, when food was restricted to less than half of conventional amount, hepatic metabolism was affected and the hepatotoxicity induced by CCl4 or CHCl3 was augmented by, at least in part, CYP2E1 induction and GSH depletion.

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© 2007 Tohoku University Medical Press
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