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Y Kera

Publications and source records attributed to Y Kera.

36 records · Page 2Linked to original sources
PubMed1988

The metabolism of acetaldehyde and not acetaldehyde itself is responsible for in vivo ethanol-induced lipid peroxidation in rats.

A single oral administration of ethanol (5 g/kg) to rats induced a marked increase in lipid peroxidation, in the liver and kidney within 9 hr, as assessed by malondialdehyde accumulation. The pretreatment with alcohol dehydrogenase (ADH) inhibitor, 4-methylpyrazole (1 mmol/kg) caused approximately 50% inhibition of the hepatic ADH activity and abolished this ethanol-induced lipid peroxidation. The disulfiram treatment (100 mg/kg) significantly inhibited 63% of the hepatic low Km aldehyde dehydrogenase (ALDH) but not the high Km ALDH. The cyanamide treatment (15 mg/kg) effectively decreased 83% of the low Km and 70% of the high Km ALDH in the liver. Although there was more than a 20-fold elevation of acetaldehyde levels by the inhibition of acetaldehyde metabolism with disulfiram or cyanamide, the ethanol-induced lipid peroxidation was significantly suppressed by pretreatment with these drugs. More than 90% inhibition of xanthine oxidase and dehydrogenase by the pretreatment with allopurinol (100 mg/kg), with no effect on the hepatic ADH and ALDH activities, did not alter the enhancement of lipid peroxidation following ethanol administration. We propose that the metabolism of acetaldehyde (probably via the low Km ALDH) and not acetaldehyde itself is responsible for the ethanol-induced lipid peroxidation in vivo and that the contribution of xanthine oxidase, as an initiator of lipid peroxidation through acetaldehyde oxidation is minute during acute intoxication.

Acetaldehyde↗
PubMed1988

Glutathione replenishment capacity is lower in isolated perivenous than in periportal hepatocytes.

The zonal distribution of GSH metabolism was investigated by comparing hepatocytes obtained from the periportal (zone 1) or perivenous (zone 3) region by digitonin/collagenase perfusion. Freshly isolated periportal and perivenous cells had similar viability (dye exclusion, lactate dehydrogenase leakage and ATP content) and GSH content (2.4 and 2.7 mumol/g respectively). During incubation, periportal cells slowly accumulated GSH (0.35 mumol/h per g), whereas in perivenous cells a decrease occurred (-0.14 mumol/h per g). Also, in the presence of either L-methionine or L-cysteine (0.5 mM) periportal hepatocytes accumulated GSH much faster (3.5 mumol/h per g) than did perivenous cells (1.9 mumol/h per g). These periportal-perivenous differences were also found in cells from fasted rats. Efflux of GSH was faster from perivenous cells than from periportal cells, but this difference only explained 10-20% of the periportal-perivenous difference in accumulation. Furthermore, periportal cells accumulated GSH to a plateau 26-40% higher than in perivenous cells. There was no significant difference in gamma-glutamylcysteine synthetase or glutathione synthetase activity between the periportal and perivenous cell preparations. The periportal-perivenous difference in GSH accumulation was unaffected by inhibition of gamma-glutamyl transpeptidase or by 5 mM-glutamate or -glutamine, but was slightly diminished by 2 mM-L-methionine. This suggests differences between periportal and perivenous cells in their metabolism and/or transport of (sulphur) amino acids. Our results suggest that a lower GSH replenishment capacity of the hepatocytes from the perivenous region may contribute to the greater vulnerability of this region to xenobiotic damage.

Amino Acids↗
PubMed1988

Depletion of hepatic glutathione by ethanol occurs independently of ethanol metabolism.

The mechanism of ethanol-induced depletion of hepatic glutathione (GSH) was studied in vivo and in isolated hepatocytes. Neither inhibition of ethanol metabolism with 4-methylpyrazole, nor a 10-fold elevation of acetaldehyde levels by inhibition of aldehyde dehydrogenase with cyanamide or disulfiram, affected the magnitude of the GSH depletion observed in vivo. The rate of intracellular GSH accumulation by isolated hepatocytes incubated with cysteine or methionine was not inhibited by the addition of 80 mM ethanol. A significantly decreased rate of GSH accumulation was, however, found in hepatocytes isolated from ethanol-intoxicated animals. Neither the in vivo pretreatment with ethanol nor its in vitro addition to isolated hepatocytes affected the rate of GSH efflux. The results suggest that ethanol itself, rather than its metabolic products, causes depletion of liver GSH, and that events occurring in vivo are required for such an effect to be exerted.

Acetaldehyde↗
PubMed1987

Acinar distribution of glutathione-dependent detoxifying enzymes. Low glutathione peroxidase activity in perivenous hepatocytes.

The acinar distribution of glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and glucose-6-phosphate dehydrogenase (G-6-PDH) was examined by analyzing periportal (p.p.) and perivenous (p.v.) rat hepatocytes selectively isolated by the digitonin-collagenase perfusion. The cytosolic GST activity was higher in p.v. cells, but the microsomal GST and cytosolic GR were found to be evenly distributed in the acinus. In contrast, the activity of both the Se-dependent GPx and the microsomal (Se-independent) GPx, as well as G-6-PDH, was much lower in the p.v. than in the p.p. cells. The heterogeneous distribution of GST, GPx and G-6-PDH was confirmed by analyzing liver perfusion effluents collected after ante- or retrograde digitonin infusion. The relatively low activities of GPx and G-6-PDH in the p.v. cells could partly explain the susceptibility of this region to chemical injury.

Animals↗
PubMed1987

Glutathione metabolism in isolated rat hepatocytes: acinar heterogeneity of detoxifying enzymes and effects of ethanol.

Periportal and perivenous hepatocytes were isolated by the digitonin-collagenase perfusion technique. The activity of the cytosolic glutathione S-transferase was higher in perivenous cells, but the cytosolic glutathione reductase and the microsomal glutathione S-transferase activities were evenly distributed. In contrast, both the Se-dependent and the microsomal Se-independent glutathione peroxidase activity and the glucose-6-phosphate dehydrogenase activity was much lower in perivenous hepatocytes, suggesting that these cells have a lowered detoxification capacity, which may contribute to their greater susceptibility to damage by xenobiotics. The mechanism of the ethanol-induced GSH depletion in vivo was studied by incubating conventionally isolated hepatocytes. In the absence of glutathione precursors, ethanol (80 mM) did not influence the GSH content, despite accumulation of acetaldehyde (10-100 MicroM). L-Methionine or L-cysteine stimulated GSH replenishment to in vivo rates. Ethanol oxidation resulted in acetaldehyde accumulation, but did not inhibit GSH replenishment from L-methionine and even stimulated that from L-cysteine. This seems to exclude conjugation of GSH with acetaldehyde as a mechanism by which ethanol suppresses GSH levels in vivo.

Animals↗
PubMed1985

Conjugation of acetaldehyde with cysteinylglycine, the first metabolite in glutathione breakdown by gamma-glutamyltranspeptidase.

Glutathione and its metabolites were examined for reactivity to acetaldehyde. When acetaldehyde was incubated with glutathione alone, there was only a slight decrease of acetaldehyde, while an apparently equimolar reaction between acetaldehyde and free sulfhydryl was observed with the addition of gamma-glutamyltranspeptidase. Cysteinylglycine, the first metabolite in the glutathione breakdown by gamma-glutamyltranspeptidase, showed a rapid and equimolar reactivity to acetaldehyde and such was comparable to the reaction seen with L-cysteine or D-penicillamine. In light of the chemical structure, cysteinylglycine probably conjugates with acetaldehyde to form thiazolidinecarboxylic acid derivatives, 2-methyl-thiazolidine-4-carbonyl-glycine, and if so, the alteration of glutathione metabolism by acetaldehyde during ethanol intoxication warrants further attention.

Acetaldehyde↗
PubMed1985

Suppression of acetaldehyde accumulation by 4-methylpyrazole in alcohol-hypersensitive Japanese.

Alcohol-sensitive Japanese subjects with facial flushing and an increase in heart rate during ethanol intoxication exhibited marked individual variation in accumulation of acetaldehyde. This variation correlated well with the intensity of the above mentioned physiological responses. Oral pretreatment with 10 mg/kg 4-methylpyrazole, which inhibited the ethanol elimination rate by 15-25%, strongly suppressed both acetaldehyde accumulation and the associated responses. Under this condition, the sensitivity to acetaldehyde appeared to be reduced, and the correlation between the acetaldehyde level and the physiological responses disappeared. The effectiveness of even a low dose of 4-methylpyrazole suggests its clinical usefulness for alleviation of acute acetaldehyde toxicity in alcohol-hypersensitive Japanese individuals as well as in disulfiram-treated alcoholics.

Acetaldehyde↗
PubMed1985

Ethanol induced changes in lipid peroxidation and nonprotein sulfhydryl content. Different sensitivities in rat liver and kidney.

Acute ethanol ingestion (5 g/Kg) led to an acceleration of lipid peroxidation and reduction in non-proteinic free sulfhydryl (NPFSH) levels in the rat liver and kidney. In the liver, progressive changes of these phenomena were inversely related, and maximal effects were observed 6 hr after ethanol ingestion. Unlike the liver, in the kidney, there was a rapid fall in NPFSH content followed by constantly reduced levels during ethanol intoxication, whereas acceleration of lipid peroxidation was detected only after 6-8 hr of ethanol. In addition, a lower dose (2 g/Kg) which caused no significant change in the liver, was effective in reducing renal NPFSH, but not in enhancing lipid peroxidation. These results suggest that acceleration of lipid peroxidation may not be required for the NPFSH decrease, at least in case of kidney.

Animals↗
PubMed1983

Comparative study of phenotypes on activity and plasma concentration in the genetic system of plasminogen.

Plasma antigen concentration of plasminogen was approximately 11-13 mg/100 ml in all phenotypes. Specific activities of common PLG 1-1 and second common PLG 2-1 were 16.52 +/- 1.43 U/mg (caseinolytic activity/milligram antigen concentration, mean +/- SD) and 17.22 +/- 2.14 U/mg, respectively. Caseinolytic activity, antigen concentration and specific activity of PLG 1-B were 0.80 +/- 0.23 U/ml, 11.39 +/- 2.44 mg/100 ml and 6.95 +/- 0.96 U/mg. Plasma plasminogen levels of three rare phenotypes (PLG 3-1, PLG 1-C and PLG 1-M) were at least in the normal ranges by immunological and biological assay.

Alleles↗
PubMed1982

Two new slow-moving variants of human serum albumin.

Two new slow-moving variants of human serum albumin were found in members of two unrelated Japanese families. These variants, different from each other and from the slow-moving variants described previously, were designated albumin "Okinoerabu' and albumin "Akasaka'. The mode of inheritance of each variant was consistent with an autosomal codominant trait. A very rare type, homozygote for a variant, albumin "Okinoerabu', was also detected. The segregation data of albumin and Gc showed no discrepancy from the postulation of a linkage between these two loci.

Electrophoresis, Agar Gel↗
PubMed1982

Three new variants in the plasminogen system.

Three new phenotypes of plasminogen system, named PLG 3-1, PLG 1-M and PLG 1-C, were found in sera from healthy Japanese persons by the agarose gel isoelectric focusing followed by the methods of immunofixation and caseinolysis. The present study indicates that at least the PLG 3 component is genetically determined. The existence of another PLG3 allele is postulated.

Adult↗