vitamin-k-semiquinone-radical and Carbon-Tetrachloride-Poisoning

The effect of vitamin K on carbon tetrachloride-induced cellular damage of primary cultured hepatocytes was investigated by estimating prothrombin activity as a parameter of cellular function. Prothrombin activity was evaluated in primary cultured rat hepatocytes using synthetic fluorogenic peptide substrates (Boc-Val-Pro-Arg-MCA). Prothrombin activity significantly increased with the addition of vitamin K and decreased by the addition of warfarin (P less than 0.05). Carbon tetrachloride caused a significant decrease of prothrombin activity and cytotoxicity in a dose dependent manner. Prothrombin activity increased after addition of vitamin K when cells were previously exposed to carbon tetrachloride for a short period, but there was no change in cells treated for a long period. Carbon tetrachloride caused a modest increase of malondialdehyde formation after a short period of exposure and a significant increase following a long period of exposure. These results suggest that: 1) prothrombin activity is a good parameter for protein synthesis in cultured hepatocytes, 2) carbon tetrachloride-induced cytotoxicity results from different mechanisms in the early phase and the late phase of exposure, and 3) vitamin K has the ability to protect hepatocytes against the carbon tetrachloride-induced cellular damage in the early phase.

Topics: Animals; Carbon Tetrachloride Poisoning; Cells, Cultured; Chemical and Drug Induced Liver Injury; Liver; Male; Prothrombin; Rats; Vitamin K

Topics: Animals; Carbon Tetrachloride Poisoning; Cells, Cultured; Liver; Prothrombin; Rats; Vitamin K

Isolated rat liver cells have been exposed to 3 different lipid peroxidation-inducing agents, CCl4, FeCl3 and cumene hydroperoxide, and the rates of malonaldehyde production and of lipoprotein secretion have been compared. Results indicate that it is possible to induce a high degree of lipid peroxidation without inducing strong changes in lipoprotein secretion. Only in CCl4-poisoned hepatocytes is lipoprotein secretion strongly impaired. In this experimental condition, the effect of free radical scavengers, or inhibitors of lipid peroxidation, as well as the behavior of both lipid peroxidation and lipoprotein secretion, have been evaluated. Promethazine and propyl gallate prevented malonaldehyde production, but neither agent reduced covalent binding nor improved secretion. Menadione, on the contrary, besides inhibiting malonaldehyde production, decreased covalent binding and protected against the impairment of secretion. These data lead to the conclusion that covalent binding of CCl4 metabolites, rather than lipid peroxidation products, accounts for the derangement of lipoprotein secretion in CCl4-poisoned liver cells.

Topics: Animals; Benzene Derivatives; Carbon Tetrachloride Poisoning; Chlorides; Ferric Compounds; Lipid Peroxides; Lipoproteins; Liver; Male; Malondialdehyde; Palmitic Acid; Palmitic Acids; Promethazine; Rats; Rats, Inbred Strains; Vitamin K

Topics: Aminocaproates; Animals; Blood Coagulation; Blood Coagulation Tests; Carbon Tetrachloride Poisoning; Cellulose; Collagen; Gastrointestinal Hemorrhage; Hemorrhage; Hemostatics; Injections, Intravenous; Liver; Powders; Rats; Tissue Extracts; Vitamin K

Topics: Adrenochrome; Aminocaproates; Animals; Antifibrinolytic Agents; Carbon Tetrachloride Poisoning; Cyclohexanecarboxylic Acids; Dicumarol; Ethylamines; Factor Analysis, Statistical; Hemorrhagic Disorders; Hemostatics; Hydroquinones; Male; Phenols; Rats; Semicarbazones; Sulfonic Acids; Vitamin K; Vitamin K 1

After hepatic injury induced by carbon tetrachloride, mitotically active hematopoietic cells of nonhepatic origin localize in the liver as judged by an increase in colony-forming nodules in the spleens of lethally irradiated recipient mice on intravenous injection of cells from these livers. The administration of warfarin suppresses the localization of colony-forming units in the regenerating liver by inhibiting the coagulation mechanism of the donor animals.

Topics: Animals; Blood Coagulation; Bone Marrow Cells; Carbon Tetrachloride Poisoning; Female; In Vitro Techniques; Liver Regeneration; Mice; Spleen; Subcellular Fractions; Vitamin K; Warfarin

Topics: Alanine Transaminase; Animals; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Liver; Liver Function Tests; Rats; Thioctic Acid; Transaminases; Vitamin A; Vitamin K; Vitamins

Topics: Adrenal Cortex; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Diet, High-Fat; Humans; Lipids; Liver; Pancreas; Spleen; Thioctic Acid; Vitamin K; Vitamins

Topics: Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Thioctic Acid; Vitamin A; Vitamin K; Vitamins