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Protection of regenerating liver after partial hepatectomy from carbon tetrachloride hepatotoxicity in rats: Role of hepatic stimulator substance
Author(s) -
Zhang BaoHong,
Gong DeZheng,
Mei MaoHua
Publication year - 1999
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.1999.01992.x
Subject(s) - carbon tetrachloride , ccl4 , in vivo , liver regeneration , bilirubin , pharmacology , hepatectomy , in vitro , medicine , chemistry , endocrinology , biochemistry , biology , regeneration (biology) , surgery , microbiology and biotechnology , organic chemistry , resection
Background: In the present study, we examined the effect of hepatic stimulator substance (HSS) on modulating hepatotoxicity induced by carbon tetrachloride (CCl 4 ) in the regenerating rat liver.Methods: Hepatotoxicity was induced in vivo by administering CCl 4 to rats that had undergone a 68% partial hepatectomy (PH). In vitro studies were also performed in hepatocytes isolated from PH rats.Results: Hepatic stimulator substance was extracted from regenerating rat liver 96 h after PH and its activity, as determined according to the method of LaBrecque, reached its maximum 96 h after PH. At this time, the mortality induced by CCl 4 was significantly decreased in PH rats compared with sham‐operated rats (18 vs 59%, P < 0.01). Likewise, changes in serum alanine aminotransferase (ALT) or bilirubin induced by CCl 4 were less in rats after 96 h PH. The resistance of regenerating hepatocytes to CCl 4 was retained in in vitro samples. Thus, leakage of intracellular ALT or aspartate aminotransferase induced by CCl 4 in hepatocytes from 96 h hepatectomised rats was less than in control hepatocytes. HSS demonstrated a protective effect on hepatocytes against CCl 4 both in vivo and in vitro . In additional studies, regenerating liver showed increased mitochondrial respiratory activity and enhanced plasma membrane fluidity. The HSS was also shown to increase hepatic mitochondrial respiratory activity and enhance plasma membrane fluidity. Further, the protective effect induced by HSS was correlated with the restoration of mitochondrial respiratory activity and plasma membrane fluidity induced by CCl 4 .Conclusions: Regenerating rat liver exhibits resistance to CCl 4 ‐induced hepatotoxicity, and the protection afforded by the regenerating state can be attributed, at least in part, to HSS‐induced increases in mitochondrial respiratory activity and plasma membrane fluidity. © 1999 Blackwell Science Asia Pty Ltd