Further observations upon the effects of phenobarbital pretreatment on the hepatotoxicity of carbon tetrachloride

Richard J. Stenger, Elizabeth A. Johnson

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17 Scopus citations


Male rats received injections of phenobarbital on each of 4 successive days, while controls were given saline. At 1 day after the last injection, phenobarbital-treated rats displayed a marked proliferation of hepatic smooth endoplasmic reticulum and a significant reduction in hexobarbital-induced sleeping time. When phenobarbital- and saline-treated rats were tested at 8 days after their last injection, there was no difference in sleeping times, but hepatic smooth endoplasmic reticulum was still abundant in the drug-treated animals. When phenobarbital-treated rats were given carbon tetrachloride (CCl4) at 1 day after their last drug injection, there followed a 77% mortality and the livers of such animals showed massive or submassive hepatic necrosis. If the CCl4 challenge was delayed until the eighth day after the last phenobarbital treatment, there was no mortality and the livers of such rats exhibited only a limited centrilobular zone of parenchymal injury, similar to that of the control groups. Those findings indicate that the proliferated hepatic smooth-surfaced membranes per se cannot be held responsible for the observed differences in CCl4 hepatotoxicity. Rather, the results support the concept that hepatic drug-metabolizing enzyme systems are involved in the hepatotoxic responses to CCl4 administration.

Original languageEnglish
Pages (from-to)220-227
Number of pages8
JournalExperimental and Molecular Pathology
Issue number2
StatePublished - Apr 1971
Externally publishedYes


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