A bio-defensive function induced by low-dose lipopolysaccharide pre-treatment against CCl4-induced fulminant hepatic failure in rats.

We have investigated the bio-defensive function of low-dose LPS pretreatment on CCl4-induced fulminant hepatic failure (FHF) in rats. In male Donryu rats treated with CCl4 at 1.0 ml/kg i.p., the serum alanine aminotransferase (ALT) increased up to a peak at 24 h. The increase in intracellular Ca2+ concentration was biphasic, i.e., a first peak at 1 h and a second at 3 days. However, when rats were treated daily with CCl4 at 1.0 ml/kg, serum ALT successively increased over several h after the second administration, but the rats died of FHF. The first Ca2+ peak occurred 1 h after CCl4 administration, but the concentration did not increase continually, until it reached the second peak. However, rats did not die when they were treated with lipopolysaccharide at 0.5 mg/kg 24 h prior to the initial dose of CCl4 at 1.0 ml/kg. The serum ALT value did not increase after administration of CCl4 at 1.0 ml/kg, but the second Ca2+ peak was sustained at > 1, 000 nM. We concluded that the second Ca2+ peak acts to protect the liver from injury.