Effect of phenobarbital pretreatment on the hepatotoxicity of carbon tetrachloride in rat

Byun, Young Soo; Nam, Hae Joo; Kim, Mi Jin; Kim, Dong Suk; Choi, Won Hee; Lee, Tae Sook

Abstract

The purpose of this study was to evaluate the influence of phenobarbital (PB) on hepatotoxic effect of carbon tetrachloride (CCI4) which induces centrilobular necrosis in liver. Rats were injected intraperitoneally CCI4 dissolved in olive oil by a dose of 0.4 mg/kg. For change related to PB pretreatment, rats were injected CCIâ‚„ 0.4mg/kg after PB pretreatment. The liver samples were taken in 6, 12, 24, 48, 72 and 120 hours after CCIâ‚„ and/ or PB injection. Extracted liver tissue was examined with light and electron microscopes. The results were summarized as follows: 1. Light microscopic findings: In CCIâ‚„ group, centrilobular necrosis developed from 6 hours after injection, was the most severe in 48 hours, and recovered after 72 hours. In addition to necrosis, fatty change and pale cell change were accompanied. In PB-CCI4 group, necrosis occurred from 6 hours after CCIâ‚„ injection and continued to 72 hours, and the degree of necrosis was more severe than that of CCIâ‚„ group and pale cell change was decreased. 2. Electron microscopic findings: In CCI4 group, the early principal change was clumping and vesicular dilatation of endoplasmic reticulum. In PB-CCIâ‚„ group, the degenerative change of endoplasmic reticulum was aggravated and the mitochondria also revealed severe degenerative change. According to the results, it was revealed that CCIâ‚„ hepatotoxicity primarily began with the damage of endoplasmic reticulum, then damage of other cell organelles and cell necrosis followed, and these cytotoxic effects were aggravated by PB pretreatment.