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)

The specific activities of D-3-hydroxybutyrate dehydrogenase (BDH) and glutamate dehydrogenase (GDH) are reduced in the liver and kidney of rats intoxicated with 2.5 mg Cd/kg body wt and sacrificed after 24 h; conversely ketone-body concentration is strongly increased in both of these organs and blood. In the same animals a great stimulation of antioxidant enzymes glutathione reductase and glutathione peroxidase occurs. The prooxidant state induced by cadmium in liver mitochondria and microsomes is unaffected by superoxide dismutase, catalase, or mannitol, whereas it is completely blocked by vitamin E thus excluding the involvement of reactive oxygen species in this process. The mechanism by which cadmium induces lipid peroxidation has been investigated by measuring the effect of this metal on liposomes. Ninety-minute treatment of liposomes with CdCl2 does not induce any lipid peroxidation. In contrast, Fe2+ ions under the same conditions cause strong liposome peroxidation. It has also been observed that cadmium promotes a time-dependent iron release from biological membranes. When lipid peroxidation is induced by a low concentration (5 microM) of FeCl2, in place of CdCl2, the characteristics of this process and the sensitivity to the various antioxidants used are similar to those observed with Cd. From these results we conclude that the prooxidative effect of cadmium is an indirect one since it is mediated by iron. With regard to the inhibitory effect on BDH and GDH following cadmium intoxication, it does not appear to be imputable to lipid peroxidation since in vitro investigations indicate that the presence of vitamin E does not remove the inhibition at all.
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PMID:Enzyme activity alteration by cadmium administration to rats: the possibility of iron involvement in lipid peroxidation. 934 63

Livers of fasted rats were perfused over 120 min in a recirculating hemoglobin-free system. Hepatotoxic injury induced by the addition of 1-butanol (130.2 mmol/l), CdCl2 (0.1 mmol/l), CuCl2 (0.03 mmol/l), Na3VO4 (2 mmol/l) or t-butylhydroperoxide (t-BuOOH, 0.5 mmol/l) to the perfusate was shown by strong increases in lactate dehydrogenase (LDH) and glutamate-pyruvate transaminase (GPT) release, decreased oxygen consumption between 50 and 60%, and a nearly complete suppression of bile flow. Hepatic adenosine triphosphate (ATP) and reduced glutathione (GSH) concentrations were reduced by between 30 and 80%, and 20 and 80% respectively. Only Na3VO4 and t-BuOOH evoked increased releases of glutamate dehydrogenase (GLDH) in the perfusate. Malondialdehyde (MDA) concentrations were enhanced by all toxicants in the perfusate and by all except 1-butanol in the liver. The MDA increase, however, was much higher after Na3VO4 and t-BuOOH than after the other toxicants. When glycine (12 mmol/l) was added 30 min before the toxicants to the perfusate it prevented the enzyme releases induced by all hepatotoxic agents by about 80%. Furthermore, glycine prevented the Na3VO4 induced increase of MDA in liver and perfusate, the hepatic ATP and GSH level reductions induced by 1-butanol and attenuated the reduction of oxygen consumption induced by CuCl2 and t-BuOOH. Glycine, however, did not reverse the reductions of oxygen consumption induced by CdCl2 and Na3VO4, the suppressions of bile flow and, with the exception of 1-butanol, the decreases of hepatic ATP levels induced by all agents.
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PMID:Influence of glycine on the damage induced in isolated perfused rat liver by five hepatotoxic agents. 970 6

Twelve male and female Wistar rats each received cadmium (as CdCl2) in their diet at concentrations of 0, 10, 50, and 250 ppm for 72 weeks. After 1, 4, 8, 13, 18, 26, 32, 45, 57, and 68 weeks a total of 8 enzymes from different cellular compartments of the nephron were measured. At the end of the study period, the kidneys were examined histopathologically. Concentrations up to and including 50 ppm did not induce any adverse effect. At 250 ppm, growth of male and female animals was markedly retarded. Significantly increased activities of the cytosolic phosphohexose isomerase were excreted by males and females receiving 250 ppm at all timepoints from week 13. The values of the mitochondrial glutamate dehydrogenase were mostly elevated from week 1 to 57, however, due to a wide scatter range, were only occasionally significantly different from control values. The brush border enzymes (gamma-glutamyl transferase, alkaline phosphatase and leucine arylamidase) were not changed in a relevant manner in female rats, while in 250 ppm males the excreted activity of ALP and LAP from week 1 to week 18, and that of GGT during the entire study period were significantly lower than the control values. Excretion of the lysosomal enzymes aryl sulfatase A, beta-galactosidase, and beta-N-acetyl-D-glucosaminidase was at no time influenced in a noteworthy manner. Histopathology after 72 weeks revealed chronic but also acute degenerative changes in the kidneys of 250 ppm males and females. A comparison of published data on persons having undergone high cadmium exposure with the results presented here shows remarkable differences.
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PMID:Time course of chronic oral cadmium nephrotoxicity in Wistar rats: excretion of urinary enzymes. 1053 56