Abstract

Fasting can up regulate the expression of cytochrome P450 2E1 and induce glutathione levels to decrease, protecting the liver from hepatotoxic agents. The aim of this study was to research the mechanism of fasting aggravates isoniazid induced liver injury in mouse. 7 w old male C57 black 6 mice were randomly assigned to two groups: mice fed ad libitum on commercial chow (A group) and mice fasted for 12 h during the day and fed ad libitum on commercial chow (F group). All animals were administered with 100 mg/kg of isoniazid daily by gavage for 6 w (isoniazid levels were selected on basis of screening multiple concentrations). Sera were collected to measure biochemical parameters. Liver sections were stained with hematoxylin and eosin to evaluate hepatic histology. Cytokines was detected by cytometric bead array, flow cytometry. Isoniazid administration (100 mg/kg) daily for 6 w did not significantly induce histological damage in mice of A group. Compared with normal mice, there was no significant difference in serum alanine aminotransferase and aspartate aminotransferase. However, the level of alanine aminotransferase and aspartate aminotransferase levels in F group remained elevated for 6 w, reached its peak on the 3^rd d and gradually returned to normal. The liver sections revealed hepatic edema around the central vein on the 3^rd d. At 1^st or 2^nd w, hepatic edema around the central vein with inflammatory cell infiltration and focal necrosis was present. After 4 w, liver histology gradually recovered. Fasting condition influences the cytokine concentration in peripheral blood and liver tissue.