The influence of single oral dose of anti-inflammatory, antipyretic and analgesic agents on urinary enzymes was investigated in rats as a indicator of nephrotoxic effect. Urinary LDH activity was significantly elevated by aspirin, ketophenylbutazone, aminopyrine, phenacetin and acetaminophen. These drugs increased also H/M ratio of LDH isoenzymes. Although other test drugs have no effect on LDH in urine phenylbutazone and indomethacin elevated GPT and Al-P, oxyphenbutazone did γ-GT and anthranilic acid derivatives did Al-P and γ-GT. Other drugs such as sodium salicylate, ibufenac, ibuprofen, bucolome, aminopropylone, sulfinpyrazone, benzydamine and mepirizole did not significantly influence any enzyme activities measured in urine.
Administration of chloropeptide, a hepatotoxic cyclic pentapeptide of Penicillium islandicum Sopp, caused a marked decline in the hepatic glycogen synthetase activity with concominant increase in NADP-dependent G-6-P dehydrogenase activity. The microsomalmixed function oxygenases were also reduced in the liver of rats following chloropeptide treatment.
The toxicity of toluene was evaluated in male mice by the narcotic effects and lethality. The i.p. LD50 of toluene for male mice was calculated to be 1.15g/kg according to the method of Weil. Pretreatment with phenobarbital, produced a marked decrease in the number of sleep induced by a test dose (0.96 g/kg i.p.) of toluene. By contrast, pretreatment with a variety of hepatic enzyme inhibitors such as CCl4, SKF 525A, pyrazole and cyanamide was found to produce an increase in the number of sleep and death, accompanied with the prolongation of sleeping time. The present results suggest that the toxicity of toluene is enhanced by the inhibition of any step of metabolism. Toluene is an organic solvent which has been used widely in industry and is contained in thinner as its major constituent.
The in vitro transfer of DDT through various media to rat adipose tissue was examined. About 15% of DDT was transferred through Krebs-Ringer solution to the tissue slices after 2-hr incubation at 37°C. The addition of albumin accelerated the transfer of DDT proportionally to the concentrations up to 1.0 %. Hemoglobin and γ-globulin showed a lesser accelerating activity, but protamine, trypsin and pepsin showed little or no effect. When the Krebs-Ringer solution was replaced by triglyceride suspensions, only a small amount of DDT was taken up by the adipose tissue. Ffflux experiments revealed that the adipose tissue scarcely released DDT into albumin solution or triglyceride suspensions. The results suggest that lipid may play an important role as a storage site of DDT and that albumin may behave as a carrier system.
Zinc ion, Cu2+ and Cd2+ at 10-4M or lower concentrations caused a marked decrease in the membrane potential of mucous epithelial cells in the isolated newt stomach without appreciable change in the effective membrane resistance and electrical coupling ratio. Cysteine and acetylpenicillamine antagonized the action of these ions. These ions as well as ouabain blocked the hyperpolarization of membrane due to an increase in intracellular Na+. The effect of the ions on the relationship between external K+-concentration and membrane potential was similar to that of ouabain. Discussion is made on the possibility that the ions inhibit active ion transport by combining with a SH-group of the cell mem brane and, thus, bring about a decrease in membrane potential.
The detoxication of 4-iodothymol was investigated in man. A new metabolite was isolated as a crystalline derivative from 4-iodothymol medicated urine and identified as 4-iodothymol glucuronide as a methyl acetyl derivative. The deiodinated metabolite of 4-iodothymol, thymoquinone, was also recognized in a very small amount in 4-iodothymol medicated urine.
The cytological changes induced in the spinal cords of rabbits by intracisternal injections of aluminum chloride have been studied at the light- and electron-microscopic level for examining the progress of the 100Å filament hypertrophy. A moderate increase in the number of the 100Å filament was detected in perikarya of neurones in anterior, lateral, and dorsal horns 4-5 days after aluminum injection. Tangles of 100Å filament were seen in perikarya and proximal parts of dendrites in these neurones 1-2 weeks after the administration of aluminum. In this stage the tangles were detected as large clear spots at light-microscopic level. The 100Å filament bundles developed in between clumps of densely aggregated endoplasmic reticulum keeping close contact with this and squeezing other organella out. In high resolution studies the 100Å filament closely resembled the neurofilament in normal neurones in size and appearances and was seen to be connected with each other via side arms coming out from its wall. Relations between the endoplasmic reticulum and the 100Å filament hypertrophy was discussed referring to intoxicating effects of aluminum compounds on the nucleus of the neuron.
M73101 was given orally to pregnant mice (0, 100, 400 and 800mg/kg/day) and rats (0, 100, 300 and 600mg/kg/day) during the major organo-genesis to assess the influences of prenatal and postnatal development of progeny. There were no apparent effects of M73101 on litter size, fetal mortality or sex ratio in both species, although slight decrease in body weight occurred in fetuses of mice and rats exposed to the largest dose. No external, intemal or skeletal malformations attributable to M73101 were observed in mouse and rat fetuses. No apparent influences of M73101 on postnatal development of mouse or rat offspring were seen.
Subacute toxicity test of AMI-U-II was carried out using male and female JCL:SD rats. The animals were given intravenously AMI-U-II(80, 40 and 20ml/kg) or reference solution (80 and 40ml/kg) for five weeks. Tachypnea, depression of spontaneous activity, blephdroptosis and edema of face were observed in rats treated with AMI-U-II or reference solution at highest dose. Food consumptions and gaining body weight were slightly reduced in male of these animals, but water intakes were increased in both sexes. Autopsies of the animals which died during five weeks showed pulmonary congestion and/or edema, ascites and pleural effusion. Microscopically, hydropic degeneration of liver cells and dilation of renal tubules and Bowman's capsules were shown. It seems likely that most of these findings were caused by hypervolumic administration of amino acid solution.