Sadao Iguchi

Intrahepatic Delivery of Glutathione by Conjugation to Dextran

Glutathione was covalently attached to dextran (T-40) by the CNBr activation method. The compound obtained was a water-soluble powder containing 10 (w/w%) glutathione, which was gradually released from the conjugate in aqueous media. Mice depleted of glutathione by treatment with buthionine sulfoximine, a potent inhibitor of γ-glutamylcysteine synthetase, exhibited a significant increase in hepatic glutathione level after intravenous injection of the conjugate. In mice given a lethal dose of acetaminophen, the survival rate increased progressively with coadministration of the conjugate, whereas little improvement was found when free glutathione was given. The conjugate maintained the serum transaminase activities at lower level after acetaminophen administration. These findings suggest that the dextran conjugate of glutathione is transported into hepatic cells and is intracellulary hydrolyzed to free form, which protects mice from hepatotoxicity due to acetaminophen.

Studies of isoniazid metabolism in isolated rat hepatocytes by mass fragmentography.

Isoniazid metabolism in isolated rat hepatocytes was studied by mass fragmentography using single ion monitoring. Isoniazid and its metabolites were determined as the trimethylsilylated derivatives of acetylisoniazid and diacetylhydrazine and of the benzaldehyde hydrazones of isoniazid and acetylhydrazine. Deuterated analogues served as internal standards. Hydrazine was quantitated as benzalazine using 15N-labeled hydrazine as an internal standard. The method is well suited for the microanalysis of isoniazid metabolism, from which it was clarified that the greater part of hydrazine, a hazardous metabolite of isoniazid, was formed through the direct hydrolysis of isoniazid itself as expected.

High-performance liquid chromatographic determination of nitrite in environmental samples by the use of hydralazine

Abstract A high-performance liquid chromatographic (HPLC) procedure with UV and fluorometric detectors has been developed for the determination of nitrite by use of hydralazine. Hydralazine reacts with nitrite ion under acidic conditions at 37°C to form tetrazolo[5,1-a]phthalazine (Tetra-P) almost quantitatively. Without extraction, the determination of Tetra-P by reversed-phase HPLC was simple, specific, sensitive and reliable over the range 0.001–0.10 ppm of nitrite nitrogen. This procedure using hydralazine is one of the most useful methods for routine analysis of nitrites in foods biological fluids and ambient waters.

Increased hydrazine excretion associated with systemic lupus erythematosus

Abstract Thirty patients with systemic lupus erythematosus (SLE) were given isoniazid (INH) and their acetylation phenotypes determined. Of 30 patients, 2 were slow acetylators (7%), 28 rapid acetylators. This was approximately equivalent to the ratio in the control group (12%) and to the prevalence in the general population (10%). Urinary excretion of the metabolite hydrazine was determined in 10 SLE patients and 9 controls. The significantly higher hydrazine excretion from SLE patients as compared with that from controls suggested an aberration of metabolism in the SLE patients.

Seasonal variation in urinary excretion of aminopyrine and its metabolites in man.

The data of urinary excretion of aminopyrine and its metabolites were collected for two years using eight of male healthy volunteers. In conclusion, individual differences among subjects were remarkable. Besides, seasonal variations were demonstrated statistically.