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Biomedical subjects

H Ishiwata

Publications and source records attributed to H Ishiwata.

At least 73 records · Page 4Linked to original sources

Intestinal distribution, absorption and secretion of dimethylamine and its biliary and urinary excretion in rats.

In the gastro-intestinal tract of male Wistar rats fed a commercial diet containing 23.6 ppm dimethylamine (DMA), the concentration of DMA was highest (11.2 +/- 2.1 ppm) in the stomach and declined towards the lower regions. In contrast, the highest DMA concentration (6.6 +/- 2.5 ppm) was observed in the upper small intestine in rats fed a diet containing only 1.0 ppm DMA. DMA was absorbed in the intestines, and the disappearance curves were monoexponential. The t1/2 values for DMA in the ligated stomach, upper and lower small intestine, caecum and large intestine were 198, 8.3, 11.6, 31.5 and 11.0 min, respectively. The DMA concentration in the blood had increased to 3.0 +/- 1.0 ppm (from a pre-injection level of 0.28 +/- 0.06 ppm) 5 min after the injection of 250 micrograms DMA into the ligated upper small intestine. The disappearance curve for DMA in the blood was monoexponential and the t1/2 for the initial 15 min was 12.5 min when 250 micrograms DMA was injected into a femoral vein. The peak concentrations of DMA in the intestine and bile, respectively, were 15.6 +/- 12.6 ppm (at 15 min) and 3.7 +/- 1.9 ppm (at 30 min after the iv injection of DMA). In this 30-min period, urinary DMA increased from 17.3 +/- 9.4 to 139 +/- 23 ppm. These results show that, following ingestion, DMA is absorbed from the intestine into the blood, from which it disappears rapidly, the major part being excreted in the urine while a small proportion is excreted in the bile or secreted into the intestine, where it may be reabsorbed.

Animals↗

Absorption, secretion and excretion of dimethylamine in rats.

The dimethylamine (DMA) concentration in the gastrointestinal tract of Wistar male rats fed a commercial diet containing 23.6 mg/kg DMA was highest (11.2 +/- 2.1 mg/kg) in the stomach and decreased from the upper region to the lower region. In contrast, the highest DMA concentration (6.6 +/- 2.5 mg/kg) in the upper small intestine was observed in rats fed a low-DMA diet containing 1.0 mg/kg DMA. DMA absorption was observed in the intestines and the absorbtion curves were monoexponential. The biological half-lives (t1/2) of DMA in the ligated stomach, upper and lower small intestine, caecum and large intestine were 198, 8.3, 11.6, 31.5 and 11.0 min, respectively. The DMA concentration in blood increased from 0.3 +/- 0.1 mg/kg to 3.0 +/- 1.0 mg/kg 5 min after injection of 250 micrograms DMA into the ligated upper small intestine. The disappearance curve of DMA in blood was monoexponential and the half-life for the initial 15 min was 12.5 min when 250 micrograms DMA were injected through a femoral vein. Intestinal secretion of DMA (15.6 +/- 12.6 mg/kg) was observed 15 min after the injection. Urinary DMA increased from 17.3 +/- 9.4 to 139 +/- 23 mg/kg within 30 min of intravenous injection of DMA. These results show that the behaviour of DMA in rats is as follows: (Formula: see text)

Animals↗

Studies on nitrosamine formation by the interaction between drugs and nitrite. I. Measurement of the amount of nitrosamine formed in rat and guinea pig stomachs.

The 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 alpha tocopherol, sorbic acid and butylated hydroxytoluene was not observed in the stomach.

Aminopyrine↗

Drug-nitrite interactions: species and sex differences in the formation of dimethylnitrosamine and its effects on the hepatic enzyme activities.

Aminopyrine interacted with sodium nitrite in the stomachs of rats and guinea pigs forming dimethylnitrosamine, which affected the hepatic microsomal drug metabolism and certain hepatic enzyme activities. Sex and species differences in changes in the enzyme activities were observed after single or simultaneous administration of aminopyrine and sodium nitrite. A protective effect on dimethylnitrosamine formation with ascorbic acid and alpha-tocopherol was observed. The in vivo formation of dimethylnitrosamine by several antibiotics and an antihistaminic drug with tertiary amino group was also examined.

Aminopyrine↗

Transplacental carcinogenesis and chemical determination of 1-butyl-1-nitrosourea in stomach content after simultaneous oral administration of 1-butylurea and sodium nitrite to ACI/N rats.

Solutions of 100 mg/kg 1-butylurea and 50 mg/kg sodium nitrite were administered daily by a stomach tube to pregnant ACI/N rats from the 13th to 21st day of gestation. Neurogenous tumors were induced in their offspring. The incidence of tumours and mean survival time of rats with nervous tumours were 64% (23/36) and 309 (189672) days respectively. Localization and histological findings of the nervous tumors were similar to those observed previously in rats whose mothers received 1-butyl-1-nitrosourea (BNU) during pregnancy. Neurogenous tumors did not develop in the offspring of the mothers that received 100 mg/kg of 1-butylurea alone in the same manner. In several rats of both group, a few spontaneous tumors of the testis, pituitary gland, urinary bladder, uterus, and colon were detected. In vivo formation BNU in stomach content after intubation of 1-butylurea and sodium nitrite was determined. BNU was detected in the stomach content at levels of 25 ppm at 30 min and 23 ppm at 60 min after administration. The concentration of BNU in the stomach content corresponded to 48.3 and 29.2 microng/rat, respectively.

Animals↗