EFFECTS OF MENATETRENONE ON THE DECREASE IN CALCIUM BALANCE INDUCED BY VITAMIN-K-DEFICIENT DIET AND SODIUM LOADING IN RATS

The effects of menatetrenone (2-methyl-3-tetraprenyl-1,4-naphthoquinon e, MK-4) on calcium balance were studied in male Sprague-Dawley rats. Experiment 1: Rats in metabolic cages that were fed a vitamin K-defici ent diet and injected daily with latamoxef (100 mg/kg, i.p.) were eith er treated or untreated with MK-4 for 7 days. Daily food intake, urine volume and feces weight were determined, and calcium concentration in these samples was measured. Calcium balance was calculated as the dif ference between calcium intake and urinary and fecal calcium excretion . Cumulative calcium balance in the vitamin K-deficient group treated with latamoxef was lower than that in normal rats; this balance was si gnificantly improved by MK-4 (1 and 10 mg/kg, s.c.) administered for 7 days. Experiment 2: Rats were fed a vitamin K-deficient diet containi ng 4.6% sodium chloride for 6 weeks. MK-4 was administered as a dietar y supplement. Forty-eight-hour calcium balance, determined once a week , was significantly reduced compared with that of normal rats after 3 and 5 weeks; the balance was restored dose-dependently by MK-4 adminis tration (1 and 10 mg/kg). Experiment 3: Rats were subjected to the sam e experimental conditions as experiment 2 for 6 weeks, and intestinal calcium transport was determined using an everted gut-sac technique. C alcium transport was reduced by the high sodium, vitamin K-deficient d iet, and this reduction was restored by MK-4 administration (10 mg/kg) . These results suggest that MK-4 improves the reduced calcium balance by increasing intestinal calcium absorption in these rats.