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S Kawazoe

Publications and source records attributed to S Kawazoe.

23 records · Page 2Linked to original sources
PubMed1983

[Effect of adenosine triphosphate-magnesium chloride administration for post-ischemic acute renal failure (I)].

Models of post-ischemic acute renal failure were prepared in rats. The effects of adenosine triphosphate-magnesium chloride (ATP-MgCl2) administration following renal ischemia on possible changes in renal function and renal cellular metabolism following ischemia were studied using the model. The results obtained revealed the following: 1) Over 40 minute-renal ischemia led to significant lowerings of renal cellular ATP level and energy charge (EC) by as much as 45 to 57% and 4.1 to 7.4% of the control, respectively, at 90 min following re-establishment of renal blood flow. Significant increases in Na+ in renal tissues were observed, but no changes in K+. Further, lactate level in renal tissues tended to increase with prolonged ischemic time by as much as 27 to 31% of the control, with a renal cellular anaerobic metabolism observed. On the other hand, at 24 hr following recirculation of the kidney, plasma creatinine (P-Cr), blood urea nitrogen (BUN) and fraction excretion of sodium (FENa) increased significantly, and creatinine clearance (C-Cr) and urine osmotic pressure decreased significantly, as compared with the control, indicating ischemic acute renal failure. 2) Intravenous injection of ATP-MgCl2 at a dose of 25 mumole/kg and a rate of 1.0 mumol/min after 40 min of renal ischemia led to significant lowerings of P-Cr, BUN and FENa to 36, 35 and 35% of the control (injected with physiological saline solution), respectively, and to significant elevation of C-Cr and urine osmotic pressure by as much as 41 to 31% of the control respectively, at 24 hr after reperfusion. The above results suggested that the ischemic acute renal failure was caused by the decreases in renal cellular ATP and EC with ischemia, resulting in renal cellular metabolic disturbances. It was further suggested that ATP-MgCl2 administered for such a pathological condition could make significant improvements in renal function.

Acute Kidney Injury↗
PubMedDate not supplied

Possible role of thioformamide as a proximate toxicant in the nephrotoxicity of thiabendazole and related thiazoles in glutathione-depleted mice: structure-toxicity and metabolic studies.

In mice depleted of GSH by treatment with buthionine sulfoximine (BSO), thiabendazole (TBZ) causes renal injury characterized by an increase in serum urea nitrogen (SUN) concentration and by tubular necrosis. Previous studies have shown that TBZ requires metabolic activation before it produces nephrotoxicity and that the structure contributing to the toxicity of TBZ is the thiazole moiety of the molecule. TBZ and its thiazole analogues were examined for the ability to increase SUN concentration and serum alanine aminotransferase activity in GSH-depleted mice. Unsubstituted thiazole and thiazoles with 4- and/or 5-, and no 2-, substituents caused marked increases in SUN concentration, suggesting nephrotoxicity. Furthermore, the nephrotoxic potency of these thiazoles decreased with the increasing number and bulk of the 4- and/or 5-substituents. On the other hand, the target organ (the kidney or liver) and the toxic potency of 4-methylthiazoles were markedly altered with the type of substituents at the 2-position. These observations and the known toxicity of thiono-sulfur compounds led us to the hypothesis that the nephrotoxic thiazoles, which lack 2-substituents, would undergo microsomal epoxidation of the C-4,5 double bond and, after being hydrolyzed, the resulting epoxide would then be decomposed to form thioformamide, a possibly toxic metabolite. Evidence for this hypothesis was provided by the results that thioformamide and tert-butylglyoxal as the accompanying fragment were identified as urinary metabolites in mice dosed with 4-tert-butylthiazole and that thioformamide caused a marked increase in SUN concentration when administered to mice in combination with BSO.

Alanine Transaminase↗
PubMedDate not supplied

Formation of toxic metabolites from thiabendazole and other thiazoles in mice. Identification of thioamides as ring cleavage products.

The metabolism of three nephro- or hepatotoxic thiazoles--2-(thiazol-4-yl)benzimidazole (thiabendazole) (1a), 4-tert-butyl-2-methyl-thiazole (1b), and 2-(p-methoxyphenyl)-4-methylthiazole (1c)--was examined in mice with special regard to the formation of ring cleavage products. By GC/MS analyses of derivatized metabolites and comparison with authentic samples, thioformamide and benzimidazol-2-ylglyoxal as the accompanying fragment were identified as urinary metabolites in mice dosed with 1a. Similarly, 1b produced thioacetamide and tert-butylglyoxal, and 1c produced p-methoxy-thiobenzamide (and its S-oxide) and methylglyoxal. These results could be explained by the postulated metabolic pathways where thiazoles would undergo microsomal epoxidation of the C = C double bond and, after being hydrolyzed, the resulting epoxide would then be decomposed to form the corresponding thioamides and alpha-dicarbonyl fragments.

Animals↗