Innate host-defensive function of a hepatic lipid fraction produced in low-dose carbon tetrachloride-pretreated mice.

We investigated the tolerance of mice to carbon tetrachloride (CCl(4))-induced fulminant hepatic failure (FHF) in mice with daily intraperitoneal (i.p.) injection of high-dose CCl(4) (4 ml/kg). The tolerance was induced by preliminary i.p. administration of a low dose of CCl(4) (1 ml/kg) 24 h prior to the initial high-dose administration of CCl(4) (4 ml/kg). These mice were protected from death because of FHF induced by subsequent daily high-dose injection of CCl(4). This protection appears to result from a priming effect of the innate immune activity of CCl(4). The crude lipid extracted from the liver of low-dose CCl(4) injected mice also protected mice from death because of FHF. Examination of the innate immunological system using OK-432 (picibanil) revealed that the protection results from a priming effect of the innate immune activity with the low-dose CCl(4) or the crude lipid extract.

Characteristics of intracellular Ca2+ signals consisting of two successive peaks in hepatocytes during liver regeneration after 70% partial hepatectomy in rats.

Two specific signals for regulating liver regeneration were found after 70% partial hepatectomy (PH) in rats. The first finding was a sustained increasing signal of intracellular Ca2+ ([Ca2+]i) in hepatocytes, consisting of two successive peaks with the first narrow peak at 1 hour and the second broad peak increasing by day 3 and then returning to normal by day 4. The second finding was an abnormal peak in the restoring ratio (Rr) curve of liver regeneration after 70% PH at day 4, where the Rr exceeded 100% temporarily, returned to a lower level, and then proceeded to a termination phase of liver regeneration. For 4 days around the two successive [Ca2+]i peaks and abnormal peak, various physiological activities were induced to promote liver regeneration after 70% PH. mRNA expression of genes encoding Ca2+-binding proteins S100A4 and calpain was induced between the two Ca2+ peaks. Hepatocytes underwent synchronous cell proliferation as the liver was restored from 30% to 70% at day 4, and significant expression of VEGF mRNA at around day 4 promoted angiogenesis to remodel the sinusoidal system. Cytochrome P450 activity levels in microsomes and alanine aminotransferase values at 24 hours after CCl4 administration were decreased after 70% PH, which recovered transiently to the control level at day 4, returned to the decreased level, and then slowly recovered by day 10. Thus, these results indicate that day 4 is important during liver regeneration after 70% PH.