Vitamin K-reversible hypoprothrombinemia in rats. I. Sex differences in the development of hypoprothrombinemia and the effects of beta-lactam antibiotics.

Male-specific prolongation of prothombin time by industrial chemicals

“…Moreover, deficiencies in hepatic vitamin K caused by the decrease of vitamin K absorption may prolong PT (Jolly et al, 1977;Matsuura et al, 1988). Our database analysis clearly demonstrated that the prolongation of PT by 20 chemicals was male-specific.…”

“…These results indicate that estradiol has a protective function in the development of hypoprothrombinemia in rats. Moreover, when rats were fed a vitamin K-deficient diet, female rats required less vitamin K than male rats for prothrombin synthesis (Matschiner and Bell, 1973;Matsuura et al, 1988). Based on the evidence described above, there is a possibility that some of the chemicals and/or the metabolites in this study decrease estradiol-dependent absorption of vitamin K, thus resulting in a decrease in vitamin K concentration in the liver of male rats, which in turn, may induce male rat-specific PT prolongation.…”

“…There are several studies suggesting that deficiency of vitamin K is related to the prolongation of PT in rats. For example, male rats were more susceptible to PT prolongation than female rats on vitamin K-deficient diet (Jolly et al, 1977;Matsuura et al, 1988). In another study, administration of antibiotics prolonged PT in vitamin K-deficient female rats (Matsuura et al, 1988).…”

“…For example, male rats were more susceptible to PT prolongation than female rats on vitamin K-deficient diet (Jolly et al, 1977;Matsuura et al, 1988). In another study, administration of antibiotics prolonged PT in vitamin K-deficient female rats (Matsuura et al, 1988). PT prolongation in male rats fed a vitamin K-deficient diet was recovered by the administration of estradiol (Jolly et al, 1977;Uchida et al, 1985), since estrogen increases vitamin K absorption from the digestive tract (Jolly et al, 1977).…”

In vitro effect of beta-lactam antibiotics and N-methyl-tetrazolethiol on microsomal vitamin K epoxide reductase in rats.

“…Their data suggested that the inhibition site of antibiotics is the biosynthetic process of clotting factors in mammalian liver, but not the intestinal bacteria synthesizing menaqui nones. In the antibiotics-induced hypopro thrombinemic rats, the accumulation of endogenous substrates for gamma-glutamyl carboxylase was detected (22). However, microsomal carboxylation activity in the hypoprothrombinemic rats was not altered when the activity was determined by the use of either MK-4-H2 or MK-4 plus NAD H as a cosubstrate (5, 7, 23).…”