Influence of the vitamin D hormonal status on the hepatic response to bromobenzene

Hypocalcemic vitamin D-depleted rats received either 1,25-dihydroxy-vitamin D₃ [1,25(OH)₂D₃] or calcium p.o. in order to study the effects of plasma calcium normalization, resulting from hormone or dietary calcium administration, on the hepatic response to bromobenzene (BB). Results showed that 1,25(OH)₂D₃ administration induced a rise in the circulating aspartate aminotransferase, alanine aminotransferase and sorbitol dehydrogenase after BB administration significantly greater than in unsupplemented rats. The volumic density of necrosis was not, however, increased by 1,25(OH)₂D₃ whereas the proportion of acidophilic cells surrounding the necrotic area and the ratio of acidophilic to necrotic cells were significantly increassed suggesting the presence of regenerating parenchyma. Oral calcium yielded an increase comparable to that of 1,25(OH)₂D₃ in apparent BB toxicity which was accompanied by a significant rise in both the volumic density of necrosis and of acidophilic cells but the ratio of acidophilic to necrotic cells was not increased by dietary calcium. The amount of cytochrome P-450 lost after BB administration, the covalent binding of BB metabolites to cellular proteins in vitro and the total liver glutathione content were not changed by either 1,25(OH)₂D₃ or calcium supplementation. Results show that hypocalcemic vitamin D-depleted rats are protected partially against BB toxitiy; this protection does not seem to be due to a decrease in the hepatic metabolism of BB but seems to be related to the hypocalcemic state; on the other hand, the active regenerating process which seemed more apparent in 1,25(OH)₂D₃-treated than in all other animals may have contributed to offset partly the cellular damage induced by the toxin in the hormone-treated group.