Hepatic stimulator substance protects against acute liver failure induced by carbon tetrachloride poisoning in mice.

Abstract	Hepatic stimulator substance was extracted from the liver of weanling Sprague-Dawley rats according to the method of LaBrecque. Quang-Ming mice were injected with carbon tetrachloride to induce acute liver failure. Hepatic stimulator substance suppressed the elevation of ALT and AST induced by carbon tetrachloride in a dose-dependent manner. Hepatic histological changes indicated that hepatic stimulator substance reduced the severity of hepatic lesion induced by carbon tetrachloride and reversed carbon tetrachloride-induced reduction of hepatic mitochondrial succinic dehydrogenase activity. In attempting to elucidate the mechanism or mechanisms of this protective effect, we found that hepatic stimulator substance significantly restored the carbon tetrachloride-induced decrease of hepatocyte plasmalemma and mitochondrial and microsomal membrane fluidity. Hepatic stimulator substance also decreased the malondialdehyde content of carbon tetrachloride-intoxicated mice; restored the liver-reduced glutathione content, which was lowered by carbon tetrachloride intoxication; stimulated liver regeneration, as shown by enhanced DNA synthesis; and increased the 3H-thymidine incorporation into DNA of hepatocytes. We propose that hepatic stimulator substance protects the liver against acute liver failure induced by carbon tetrachloride poisoning, probably by an antioxidative effect on hepatocyte membrane lipid peroxidation, which was increased by free radicals produced from carbon tetrachloride. In addition, hepatic stimulator substance stimulates hepatocyte proliferation. These protective mechanisms may act in concert to protect against carbon tetrachloride injury.
Authors	M H Mei, W An, B H Zhang, Q Shao, D Z Gong
Journal	Hepatology (Baltimore, Md.) (Hepatology) Vol. 17 Issue 4 Pg. 638-44 (Apr 1993) ISSN: 0270-9139 [Print] United States
PMID	8477968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Growth Substances Intercellular Signaling Peptides and Proteins Mitogens Peptides hepatic stimulator substance Malondialdehyde Succinate Dehydrogenase Aspartate Aminotransferases Alanine Transaminase Glutathione Thymidine
Topics	Alanine Transaminase (blood) Animals Aspartate Aminotransferases (blood) Carbon Tetrachloride Poisoning (complications, pathology, physiopathology) Cells, Cultured DNA Replication Glutathione (metabolism) Growth Substances (isolation & purification, pharmacology) Intercellular Signaling Peptides and Proteins Lipid Peroxidation Liver (drug effects, metabolism, physiology) Liver Failure (etiology, pathology, prevention & control) Male Malondialdehyde (metabolism) Membrane Fluidity Mice Mice, Inbred Strains Mitochondria, Liver (enzymology) Mitogens (isolation & purification, pharmacology) Peptides (isolation & purification, pharmacology) Rats Rats, Sprague-Dawley Succinate Dehydrogenase (metabolism) Thymidine (metabolism)

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