Biochemical effects of CCl₄ on rat intestinal mucosa

1. 1. The effects of CCl₄ on the intestine were studied and compared with the effects of this agent on liver. CCl₄ caused inhibition of protein synthesis and polyribosome breakdown in rat intestine when given in vivo. In addition, dietary lipid accumulated in the intestine after CCl₄ administration. Experiments with intestinal slices demonstrated that CCl₄ inhibited protein synthesis when added in vitro. These effects were similar to those previously demonstrated in liver after CCl₄ administration both in vivo and in vitro. 2. 2. Contrary to the effects observed in the liver following the oral administration of CCl₄, the intestinal inhibition of protein synthesis produced by CCl₄ was found to be a transient phenomenon, lasting only 30-60 min. Moreover, CCl₄ led to necrosis in the liver but not in the intestine. It is suggested that these differences may be explained by the fact that CCl₄ is concentrated and retained by the liver cells, whereas this toxin may be only transiently present in the intestinal mucosa. 3. 3. ¹⁴CCl₄ was metabolized to ¹⁴CO₂ to a much greater extent by liver slices than by intestinal slices. Furthermore, while CCl₄ enhanced lipid peroxidation in hepatic subcellular fractions, no lipid peroxidation could be detected in intestinal cell fractions either in the presence of absence of CCl₄. It is suggested that, if metabolism of CCl₄ and lipid peroxidation are important for the toxic actions of CCl₄ on liver, other mechanisms must account for its effects on the intestinal mucosa. 4. 4. Pretreatment with cycloheximide partially reversed the effects of CCl₄ on protein synthesis in both liver and intestine. This effect is consistent with the hypothesis that CCl₄ produces a decreased synthesis or increased breakdown of messenger RNA.