Hepatocellular tolerance to carbon tetrachloride induced injury in the rat: a study of its nature and possible mode of evolution

Abstract

The nature and possible basis of tolerance to carbon tetrachloride hepatotoxicity have been studied in rats. The severity of injury as assessed by mortality and by structural and biochemical alterations is dose dependent. Prior exposure of animals to a 25 μl dose of carbon tetrachloride affords almost complete protection against the severe and lethal effects of a large dose of the chemical. This state of tolerance is achieved about 24 hr after the protective dose and continues for the next 48 hr. The tolerant hepatocytes appear large with vacuolated, clumped cytoplasm. Upon examination by electron microscopy, they show proliferation of rough endoplasmic reticulum and close packing of membrane-attached ribosomes, with polysomes not unlike those in perinatal liver cells. Development of tolerance is considered to be due possibly to alteration of the entire cell to a type having a different complement of enzymes, as in the fetal hepatocyte, and not to mere reduction of some key enzyme by the toxic effect of carbon tetrachloride. Certain toxic manifestations of carbon tetrachloride may well evolve through pathways different from others. Fatty change continues to occur in the tolerant animal following reexposure even though more serious pathic changes are absent or minimal.