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Volume 6, Issue 4
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Toru KAWANISHI, Yasuo OHNO, Atsushi TAKAHASHI, Hajime ISHIWATA, Akio T ...1981 Volume 6 Issue 4 Pages 261-270
Published: November 25, 1981
Released on J-STAGE: February 21, 2008
JOURNAL FREE ACCESSThe amounts of nitrosamine formed by the interaction of several drugs and nitrite in rat and guinea pig stomachs were estimated. The nitrosamine formation from aminopyrine and nitrite was much more in guinea pig stomachs than in rat stomachs. It seemed that this result was due to the difference in gastric contents of these animals. As the nitrosamine formation was also indicated in the interaction of a clinically prescribed dose of aminopyrine and very low doses of nitrite in rat and guinea pig stomachs, there is a possibility that the nitrosation of aminopyrine takes place in human stomachs, too. Minocycline also interacted with nitrite and formed N-nitrosodimethylamine. However, the amount of nitrosamine formed was less in minocycline than in aminopyrine. Oxytetracycline was not found to form nitrosamine in the stomachs of these animals. The effects of several compounds on the nitrosamine formation by the interaction of aminopyrine and nitrite were also investigated. Ascorbic acid, sodium erythorbate, propyl gallate and butylated hydroxyanisole reduced the nitrosamine formation but the effect of alphatocopherol, sorbic acid and butylated hydroxytoluene was not observed in the stomach.View full abstractDownload PDF (804K) -
Toru KAWANISHI, Yasuo OHNO, Momoko SUNOUCHI, Kin-ichi ONODA, Atsushi T ...1981 Volume 6 Issue 4 Pages 271-286
Published: November 25, 1981
Released on J-STAGE: February 21, 2008
JOURNAL FREE ACCESSThe alterations of biochemical parameters, namely, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in serum, hepatic microsomal drug oxidation systems, glucose-6-phosphate dehydrogenase and lysozomal enzymes in hepatic soluble fraction were investigated for the purpose of semiquantitatively estimating the hepatotoxicity caused by the interaction of several drugs and sodium nitrite in rats. The simultaneous administration of aminopyrine and sodium nitrite induced the alterations of these parameters. However, these alterations were not induced by the administration of antipyrine and sodium nitrite. Therefore the alterations were thought to be mainly due to N-nitrosodimethylamine formed. The administration of 0.4 mmole/kg of aminopyrine and 1.0 mmole/kg of sodium nitrite was thought to induce the alterations to almost the same extent as induced by 0.15 mmole/kg of N-nitrosodimethylamine. The simultaneous administrations of sodium nitrite and several other drugs with tertiary amino groups, namely, oxytetracycline, diphenhydramine, oleandomycin, erythromycin and minocycline induced small alterations of these parameters. However, these alterations were not thought to relate to the hepatic injury induced by N-nitrosodimethylamine. Therefore the amount of N-nitrosodimethylamine formed from these drugs in rats was thought to be rather small. We also investigated the effect of several antioxidants on the alterations of biochemical parameters induced by aminopyrine and sodium nitrite. Ascorbic acid, sodium erythorbate and propyl gallate inhibited these alterations. On the other hand, sorbic acid did not.View full abstractDownload PDF (1075K) -
Hirotoshi ITOH, Mamoru TADOKORO, Kiyoshi OIKAWA1981 Volume 6 Issue 4 Pages 287-300
Published: November 25, 1981
Released on J-STAGE: February 21, 2008
JOURNAL FREE ACCESSDelayed neurotoxicity experiments of an organophosphorus compound, TOCP, on hens and quails were carried out. The animals were orally exposed with TOCP in dose of 400 mg/kg, and maintained for 25 and 50days under observation, respectively. They were sacrificed and dissected at different periods after the exposure, and the histopathological examinations were made on those animals. During the periods of 50 days, no abnormal symptoms except for acute poisoning were noted in the quails. As to the hens, neurological disorders were observed from around 12 days of the experiment. In hens, the morphological alteration in the earlier stage of the experiment was perivascular cuffing of small round cells seen in the cerebrum, cerebellum and spinal cord. The major alteration was degeneration of axons and myelin in the white matter of the spinal cord. A minimal degree of these changes was found even in the hens in which the clinical signs of neurotoxicity had not yet been observed. Later the process expanded to the whole spinal cord as well as the sciatic nerve. The electron microscopy performed after 15 days revealed moderate change of myelin and axons. From these results, it was concluded that the clinical signs as well as the morphological changes were closely related to the exposure of the compound, TOCP.View full abstractDownload PDF (2226K) -
Junko NISHIKAWA, Alexander KAST1981 Volume 6 Issue 4 Pages 301-306
Published: November 25, 1981
Released on J-STAGE: February 21, 2008
JOURNAL FREE ACCESSAcute oral toxicity of the three Beta-adrenoceptor stimulants Orciprenalin, Fenoterol and Salbutamol as well as the two Beta-adrenoceptor blockers Pindolol and Bunitrolol was studied in singly-housed and aggregated male and female mice (ICR-JCL) and the results were compared with those in grouped mice (background studies). With a few exceptions, the acute toxic potency of the five test substance in mice appeared to be : Aggregated mice >grouped mice > singly-housed mice.View full abstractDownload PDF (550K) -
Mieko SAKAMOTO, Kazumoto CHIBA, Isao AGATA, Tamotsu HIGA, Masato KIYOT ...1981 Volume 6 Issue 4 Pages 307-314
Published: November 25, 1981
Released on J-STAGE: February 21, 2008
JOURNAL FREE ACCESSThe metabolic detoxication of bis(2-hydroxy-3, 5-dichlorophenyl)sulfoxide (BTS) in man was investigated. Bis(2-hydroxy-3, 5-dichlorophenyl)sulfide (BT) was identified in β-glucuronidase treated urine following the administration of BTS by thin-layer chromatography, gas chromatography, ultraviolet spectrum and quantitative analysis. No other metabolites were detectable. BT-glucuronide was also identified in urine. It was assumed that BTS was reduced to BT and successively conjugated with glucuronide in man, and excreted as BT-glucuronide in the urine.View full abstractDownload PDF (587K) -
Yukako OKUOKA, Atsushi ISHIHARA, Masaya TAKEUCHI, Yoshio MONMA, Tsuney ...1981 Volume 6 Issue 4 Pages 315-323
Published: November 25, 1981
Released on J-STAGE: February 21, 2008
JOURNAL FREE ACCESSIntracranial hemorrhage was induced in rats by low potent substances, glucose, NaCl and Na2SO4, intraperitoneally injected in enormous amounts, that is, 2800 mOsmol/L (J. Toxicol. Sci. 5, 290, 1980). The present study was undertaken to examine a mechanism of the above-mentioned phenomenon in detail from the aspects of the disturbance of water-electrolyte balances and the change in blood osmolality. After administration of hypertonic solutions, blood and abdominal fluid were obtained at intervals of 5 to 15 min and at death. Hypertonic solutions injected intraperitoneally induced rapid exchange in water and solutes across the peritoneum, thus causing an increase in abdominal fluid volume and plasma osmolality. Most interesting was the fact that a marked potassemia was produced and that the value of plasma potassium reached 10 mEq/L at death in all of groups of intraperitoneally injected rats. Thus, it is clear that the intracranial hemorrhage is accompanied by an increase in the plasma concentration of potassium which does not always run parallel with an increase in sodium concentration and osmotic pressure in rat plasma.View full abstractDownload PDF (659K) -
Akiko YAMAMOTO, Kyosuke YOSHIDA, Osamu WADA1981 Volume 6 Issue 4 Pages 325-333
Published: November 25, 1981
Released on J-STAGE: February 21, 2008
JOURNAL FREE ACCESSIn order to ascertain the origin of increased alkaline phosphatase in the urine of rabbits with injured proximal tubules, we studied the phosphatase by an isoenzyme examination, an inhibition test and an inactivation test. Male rabbits were daily injected subcutaneously with cadmium chloride at a dose of 1.5 mg Cd/kg/day. After treatment for three weeks, total activity of alkaline phosphatase and its isoenzyme patterns on agar-gel and disc-gel electrophoresis were examined in the liver, kidney cortex, plasma and urine, and compared with those of the control rabbits. Alkaline phosphatase activity in the urine of the cadmium treated rabbit was about eleven times higher than that of the control (p=<0.005), while enzyme activity of plasma showed almost no difference between the two groups. The isoenzyme patterns of alkaline phosphatase in both agar-gel and disc-gel electrophoresis showed that the main band of the isoenzymes of alkaline phosphatase obtained from urine of control rabbits migrated faster than that from plasma, liver, or kidney, while the main isoenzyme from urine of the cadmium group was consistent with the rapid migrating isoenzyme obtained from the kidney. Furthermore, in both groups, alkaline phosphatase activity in plasma was inactivated by the treatments of heat and urea, and inhibited by L-homoarginine, while the enzymes of the kidney and urine were not remarkably effected. The findings suggest that the increased urinary excretion of the enzyme after administration of cadmium to rabbits originates from the kidney.View full abstractDownload PDF (711K)
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