Peroxidation of lipids in serum and tissues of mice placed in low or high levels of oxygen was examined. After exposure to 100% oxygen for 3h, no significant differences were observed between control and exposed mice. However, exposure to 100% oxygen for 6h resulted in a decrease in oxygen consumption, an increase in lipid peroxides in tissues and serum, and the formation of hydroxyl radicals in tissues and serum. At low concentrations of oxygen (14% or 16%), a decrease in oxygen consumption, peroxidation of lipids and formation of hydroxyl radicals also were observed. Damage to mice was great with the lower oxygen concentrations of oxygen. There was a close correlation between the consumption of oxygen lipid peroxidation, formation of hydroxyl radicals.
The effect of taurine (TA) on acute paraquat (PQ) intoxication was investigated in rats. Treatment with TA was begun 10 min after rats received a s. c. injection of PQ 40 mg/kg. Saline (0.9 %) or 5% TA solution were infused i.v. for 5-6 min (short-interval infusion study). One hour after TA infusion, PQ concentration in the blood was increased and that in the urine was lowered, as compared with those in the saline-infused group. Significant increases of the PQ concentration was observed in kidney at 3 hours after TA administration. Excreted urine volume was significantly higher in the TA group during the time-period of 0-1 and 0-5 hours after the 5% TA administration compared with that of the saline group. However, there were no significant differences in total urinary PQ excretion between the two groups. Saline or 2.5% and 5% TA was infused continuously during the time-period of 0-1, 0-3 or 0-5 hours (long-interval infusion study). A marked increase in PQ concentration in blood and a reduction of PQ concentration in kidney were noticed during the time-period of 1-5 hours after the 5% TA infusion. Urinary excretion was remarkably accelerated by 5% TA infusion and the total urine volume increased to 20 times during the time-period 0-1 hour and 1.7 times during the time-period of 3-5 hours as compared with the saline control. In addition, urinary volume during the time-period of 0-5 hours almost reached that of 5% TA volume which infused to animals. The mortality rate of the groups that received either single or double short-time infusion of 5% TA was 100%. Thus, these results suggest that a long continuous infusion of 5% TA inceased urine output and inhibits of PQ accumulation in renal tissue despite a rise in blood PQ concentration.
S-(-)-9-Fluoro-2, 3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido-[1, 2, 3, -de] [1, 4] benzoxazine-6-carboxylic acid hemihydrate, DR-3355, a new quinolone antimicrobial agent, was administered by oral gavage to groups of ten male and ten female CD rats at dosages of 50, 200 or 800 mg/kg/day and to groups of three male and three female cynomolgus monkeys at dosages of 10, 30 or l00 mg/kg/day. Both species were treated for four weeks. The vehicle (0.5% sodium carboxymethyl cellulose)-treated group served as control. Rats at the high dose showed salivation, slight increases in total leucocyte and lymphocyte counts, slight changes in the plasma electrolyte balance, and minor reducions in urea concentration. The articular surfaces of the humerus and femur of rats at the high dose showed minor degenerative changes. Increased caecal weight occurred in rats at all the treatment groups. Monkeys at the high dose showed salivation, diarrhoea and lost weight. There was no microscopic change in the tissues examined. No effect levels under these conditions were established at 200 mg/kg/day in the rat, and 30 mg/kg/day in the monkey.