Inhibition of the high affinity Ca2(+)-ATPase activity in rat liver plasma membranes following carbon tetrachloride intoxication.

In vivo administration of CCl4 (2.5 ml/kg, body wt.) to rats results in an early and then progressive inhibition of the high affinity Ca2(+)-ATPase activity in rat liver plasma membranes. The derangement to the Ca2(+)-ATPase seems to be independent on a 'solvent effect' of the agent since the in vitro addition of increasing concentrations of either CCl4 or ethanol to control plasma membranes does not affect the enzymatic activity. By using the technique of vitamin E pretreatment of experimental animals we show that the damage to the Ca2(+)-ATPase seems to follow a two-step kinetics. The early inhibition of the enzyme is not prevented by alpha-tocopherol supplementation and seems then unrelated to lipid peroxidative processes. The same procedure is however able to affort a significant protection against the exacerbation of the damage to the Ca2(+)-ATPase becoming evident late during the course of CCl4 intoxication. The high affinity Ca2(+)-ATPase is affected in vitro by 4-hydroxy-nonenal (HNE), a major end-product of lipid peroxidation interacting with -SH groups. Similar results were obtained after the addition to the incubation medium of sulphydryl reagents. The possible mechanisms involved in Ca2(+)-ATPase inhibition are discussed in relation to the development of CCl4 toxicity and to the role of lipid peroxidative processes.