Tohoku J. Exp. Med., 2007, 212(4)

One-Day Dietary Restriction Changes Hepatic Metabolism and Potentiates the Hepatotoxicity of Carbon Tetrachloride and Chloroform in Rats

LI-QIANG QIN,¹ YUAN WANG,² JIA-YING XU,¹ TAKASHI KANEKO,³ AKIO SATO³ and PEI-YU WANG⁴

¹Department of Nutrition and Food Hygiene, School of Radiation Medicine and Public Health, Soochow University, Suzhou, China
²Internal Medicine, Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, China
³Department of Environmental Health, School of Medicine, Yamanashi University, Chuo, Japan
⁴Department of Social Medicine and Health Education, School of Public Health, Peking University, Beijing, China

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.

keywords —— dietary restriction; hepatotoxicity; hepatic cytochrome P450 2E1; chloroform; carbon tetrachloride

© 2007 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2007, 212, 379-387

Correspondence: Pei-Yu Wang, Department of Social Medicine and Health Education, School of Public Health, Peking University, Xueyuan Road 38, Haidian District, Beijing, 100083, China.

e-mail: qinliqiang0326@yahoo.com.cn