Effect of vitamin K on carbon tetrachloride-induced cellular damage in primary cultured rat hepatocytes.
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.
Itoh
Y
Y
Second Department of Internal Medicine, School of Medicine, Dokkyo University, Tochigi, Japan.
Terano
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A
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology*; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011516:Prothrombin / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014812:Vitamin K / Q000494:pharmacology*
D014812:Vitamin K; D011516:Prothrombin