Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.4.1.2 (glutamate dehydrogenase)
 4,380 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An isomeric mixture of S-[(1 and 2)-phenyl-2-hydroxyethyl]glutathione (PHEG), a glutathione conjugate of styrene, is moderately nephrotoxic. Its in vivo nephrotoxicity was characterized by significant elevations in the urinary excretion of glucose, gamma-glutamyl transpeptidase, glutamate dehydrogenase, N-acetyl-beta-D-glucosaminidase and lactic dehydrogenase 24 h after an i.v. administration of PHEG (0.5 mmol/kg) in male Fischer-344 rats. The histologic alterations consisted of moderate tubular damage with proximal tubule vacuolization and accumulation of tubular cast material, indicating an early sign of tubular necrosis. The data suggest that nephrotoxic injury induced by PHEG lies preferentially at the tubular region of the rat kidney involving several subcellular targets. The nephrotoxicity of PHEG was blocked by acivicin, a specific inhibitor of gamma-glutamyl transpeptidase, by phenylalanylglycine, an inhibitor of cysteinylglycine dipeptidase, as well as by probenecid, a competitive inhibitor of renal organic anion transport system. On the other hand, pretreatment with aminooxyacetic acid, a specific inhibitor of renal cysteine conjugate beta-lyase, failed to inhibit the nephrotoxicity of this glutathione conjugate. Similarly, prior administration of alpha-ketobutyrate, an inducer of renal cysteine conjugate beta-lyase, failed to potentiate its nephrotoxicity, suggesting an insignificant role of beta-lyase in such toxicity. A modest decline in renal cellular GSH due to PHEG but without any concomitant oxidation of GSH to GSSG and without any increase in lipid peroxidation indicates that oxidative stress may not be an important mechanism of its nephrotoxicity. Therefore, the following steps at least, are involved in the development of its nephrotoxicity: (1) renal tubular accumulation of PHEG via a probenecid-sensitive transport process; and (2) its renal metabolism via gamma-glutamyl transpeptidase and cysteinylglycine dipeptidase to the corresponding cysteine-S-conjugate.
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PMID:In vivo nephrotoxic action of an isomeric mixture of S-(1-phenyl-2-hydroxyethyl)glutathione and S-(2-phenyl-2-hydroxyethyl)glutathione in Fischer-344 rats. 167 68

Sheep received a single intragastric dose of 0.5, 1.0, 1.5, or 2.0 mmol F-/kg. Mild signs occurred at 1.5 mmol F-/kg and the animals recovered 2 days later. With the 2.0 mmol F-/kg dose all animals showed dullness, anorexia, and mild diarrhea which decreased from the third day. Dose-related congestion of duodenum, liver, kidney, and lung was observed in all animals. For the two higher doses kidney degeneration and tubular necrosis were associated with glomerular inflammation. Serum fluoride had a dose-related increase and was still significantly elevated on Day 7 for sheep given doses higher than or equal to 1.0 mmol F-/kg. Serum calcium and glucose levels were significantly lowered for all doses on the first day and the decrease was dose-related. In sheep given 2.0 mmol F-/kg total proteins and sodium were significantly lowered, whereas potassium and urea were increased (p less than 0.05); alkaline phosphatase (ALP) and lactic dehydrogenase (LDH) were both lowered (p less than 0.01) on the first day and ALP was still lowered on Day 7. For the highest dose glutamate dehydrogenase (GDH) was increased on Days 1 and 7 and gamma-glutamyl transferase (GGT) was increased on Day 1 and lowered on Day 7. Diuresis was increased for the two higher doses in Day 3 or 4 following dosage. A dose-related increase of daily fluoride excretion occurred for all doses on Day 1 and fluoride excretion was still significantly elevated on Day 7 except for the lowest dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental acute sodium fluoride poisoning in sheep: renal, hepatic, and metabolic effects. 286 58

During the summer of 1992 renal failure was diagnosed in 232 grazing cattle in 85 herds on the west coast of Norway. The salient clinical signs were depression, anorexia and melaena or fresh blood in the faeces; diarrhoea was also commonly observed. The serum concentrations of creatinine, urea, magnesium and phosphorus, and the activities of glutamate dehydrogenase, aspartate aminotransferase and creatine kinase were above normal and the serum calcium concentration was below normal. Post mortem examinations consistently revealed renal tubular necrosis. In some cases there was liver necrosis and also erosions at the base of the tongue, in the oesophagus and in the jejunum and colon. The toxicity was probably caused by the plant Narthecium ossifragum (bog asphodel).
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PMID:Nephrotoxicity of Narthecium ossifragum in cattle in Norway. 750 63

One calf was dosed during one day with an aqueous extract from 3.0 kg (wet weight) of Narthecium ossifragum and another was dosed on the same day with the insoluble plant residue. The concentrations of serum creatinine and magnesium increased only in the calf dosed with the aqueous extract, while the activity of glutamate dehydrogenase increased only in the serum of the calf dosed with the plant residue, so differentiating the nephrotoxic and hepatotoxic principles as water-soluble and water-insoluble compounds, respectively. One calf was dosed with 30 g (wet weight) N. ossifragum flower stems per kg live weight during one day and another was dosed with 30 g (wet weight) N. ossifragum leaves per kg live weight on the same day. The serum creatinine and urea concentrations and also the activities of glutamate dehydrogenase, aspartate aminotransferase and gamma-glutamyltransferase in the serum increased in the calf dosed with the flower stems, whereas there was only a slight temporary increase in the creatinine concentration in serum from the calf dosed with the leaves. However, histopathological examination of the kidneys of the calf dosed with the flower stems revealed severe tubular necrosis and degeneration. It therefore appears that both the toxic principles are present in the flower stems of N. ossifragum rather than in its leaves. The serum creatinine concentration was significantly increased in a non-ruminating calf dosed with an aqueous extract from 32 g (wet weight) N. ossifragum per kg liveweight during one day, showing the intrinsic nephrotoxicity of the plant.
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PMID:Further studies on the presence, qualities and effects of the toxic principles from Narthecium ossifragum plants. 906 86