The thyrotoxic effect of Rose bengal (RB) (4, 5, 6, 7-tetrachloro-2', 4', 5', 7'-tetraiodofluorescein disodium salt; Food Red No. 105) was examined in male (C57BL/6N × C3H/N) F1 mice. They were given drinking-water containing RB at levels of 0 (control), 0.125 and 0.250% for 2 weeks. The effect resulted in decreases in serum levels of 3, 5, 3'-triiodothyronine (T3) and thyroxine (T4), and slight increases in serum 3, 3', 5'-triiodothyronine (rT3) levels and thyroid weight, but no difference in the values for the body-weight gain, serum thyroid stimulating hormone (TSH) levels and thyroid peroxidase (TPO) activities. However, the in vitro inhibitory effect of RB on TPO activity was observed by addition of RB to the TPO-catalyzed guaiacol oxidation. These results suggest that RB might have weak goitrogenic properties, inhibiting the peripheral conversion of T4 to T3 and/or inhibiting TPO to lead a decrease of T4 and T3 formation.
The effects of p-tert-butylphenyl trnas-4-guanidinome-thylcyclohexane carboxylate hydrochloride (NCO-650) and its metabolite, p-tert-butylphenol(BP), on the drug-metabolizing enzymes and fine structure in the rat liver were examined. Aminopyrine demethylase activity was inhibited by the administration of NCO-650 and BP at a dose of 2 and 10mg/kg, p.o. The increases of microsomal cytochrome b5 and cytochrome P-450 contents were noticed at 1, 12 and 24 hr after NCO-650 and BP administration. Ascorbate-dependent lipid peroxidation of mitochondria and microsome increased by the administration of NCO-650 and BP, but NADPH-dependent lipid peroxidation decreased by these drugs. In the morphological observations of fine structure in the liver, NCO-650 and BP caused the swelling and decrease of rough endoplasmic reticulum and the increase of smooth endoplasmic reticulum. The morphological changes of liver fine structure were related to the changes of drug-metabolizing enzymes in the liver by the administration of NCO-650 and BP, which may be suggest the transitory and functional responses of these drugs in the liver. The effect of BP on the drug-metabolizing enzymes and fine structure in the liver was similar to that of NCO-650.
Organ distribution pattern, hepatic uptake ratio, and blood clearance were examined by giving <99m>Tc-phytate (<99m>Tc-P) to the normal rats. At the same time, the relation between the severity of hepatic function and blood clearance or hepatic uptake ratio of <99m>Tc-P was studied by using the rats with acute hepatic dysfunction experimentally induced by carbon tetrachloride (CCl4) administration. Furthermore, a comparative discussion on blood clearance test of <99m>Tc-P was made with serum transaminase test and with histological test of the liver. It appeared appropriate to administer <99m>Tc-P at the dose of 500μg/kg in order to obtain an effective blood clearance curve. A major part of <99m>Tc-p intravenously administered was take up into the liver, while the remainder of small amount into the spleen, kidneys, lung, and so on. Little was recognized in the thyroid gland. The hepatic uptake ratio of <99m>Tc-P reached the maximum 15 minutes after the administration. The disappearance rate of <99m>Tc-P from blood decreased with the increase in dose of CCl4 and with the passage of time after the CCl4 administration. The blood clearance test of <99m>Tc-P showed a sensitive reaction for the acute hepatic dysfunction induced by CCl4 equally to or higher than the serum transaminase test or histological test of the liver.
In order to evalute the long-term-safety of UFT which contained tegafur [1-(2-tetrahydrofuryl)-5-fluorouracil, FT-207] and uracil in molar ratio of 1:4, a nine-month chronic toxicity study was performed in dogs. In doses of 9.7 (as FT-207 : 3mg / kg), 16.2 (as FT-207 : 5mg / kg) and 24.3 (as FT-207 : 7.5 mg / kg) mg / kg, UFT was administered orally in both sexes of dogs once a day for 9 months and withdrawn for 1 month. Three control drugs, FT-207, uracil and 5-FU, were also included in present experiment at doses of 7.5, 420.0 and 5.0 mg/ kg, respectively. In this study, the two types of toxic behaviors and symptoms were observed in UFT, FT-207 and 5-FU. The first type was the acute and / or dynamic signs and the other type was the chronic and / or static signs. Slight decrease in food consumption was observed in males at the dose levels of 24.3 mg / kg of UFT group and in both sexes of 5-FU group. In the ECG test, high T-wave was observed in some males treated with UFT, FT-207 and 5-FU. Histopathologically, micro-vacuolizations were observed in various portions of the cerebrum in both survived and dead animals treated with UFT, FT-207 and 5-FU. After one month recovery period, significant changes were not observed in various examinations, but morphological changes in the cerebrum had been remained. In conclusion, it seemed that the maximum safety dose of UFT in dogs were the 9.7 mg / kg for males and less than 9.7 mg / kg for females.
Effects of styrene on wheel-running and ambulatory activities were investigated in mice. Sixty male mice (ICR strain) were divided into 10 groups of six mice each, and they were exposed to styrene of about 930, 425, 60, 25 or 0 ppm (control group) for 4 hours a day, 5 days a week over 2 weeks. The wheel-running and ambulatory activity tests were conducted during 2 weeks of the styrene exposure, and 1 week before and after the exposure. The wheel-running activity decreased at the high concentrations (930 and 425 ppm), and the decreased activity did not recover to the control level after cessation of the exposure. In the ambulatory activity test, styrene exposure resulted in the decrease in the activity, though the change was not concentration-dependent. The present results suggest that the behavioral effect of styrene is clearly detectable by means of wheel-running and ambulatory activities in mice.