Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of antioxidants, reactive oxygen species (ROS) scavengers, and Ca2+ on cisplatin-induced renal cell injury were studied in rabbit renal cortical slices in vitro. Cisplatin induced LDH release and lipid peroxidation, inhibition of PAH uptake, and GSH depletion. These changes were significantly prevented by thiols (DTT and GSH), antioxidants (DPPD and BHA), and an iron chelator (deferoxamine). Superoxide dismutase partially reduced the cisplatin-induced LDH release without affecting the lipid peroxidation and the GSH depletion. Catalase did not affect the LDH release and the lipid peroxidation induced by cisplatin. Hydroxyl radical scavengers prevented the lipid peroxidation, whereas they did not alter the LDH release, the inhibition of PAH uptake, and the GSH depletion induced by cisplatin. Removal of Ca2+ or addition of EGTA to the incubation medium did not alter cisplatin effects on LDH release and lipid peroxidation. Buffering intracellular Ca2+ with quin-2/AM or inhibition of intracellular Ca2+ release with TMB-8 significantly reduced the cisplatin effect on LDH release without any effect on the lipid peroxidation and the GSH depletion. Ruthenium red attenuated the LDH release, the lipid peroxidation, and the inhibition of PAH uptake mediated by cisplatin. La3+ prevented the cisplatin effect on the LDH release, whereas it did not affect the lipid peroxidation, the inhibition of PAH uptake, and the GSH depletion by cisplatin. These results suggest that cisplatin induces a lethal cell injury by lipid peroxidation-dependent and -independent mechanisms and that the cell injury and the lipid peroxidation by cisplatin are iron-dependent. In addition, the data indicate that the Ca2+ released from intracellular stores, but not the Ca2+ moved from extracellular space, plays a role in the cisplatin-induced cell injury independent of lipid peroxidation.
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PMID:Effects of antioxidants and Ca2+ in cisplatin-induced cell injury in rabbit renal cortical slices. 934 94

Ascorbic acid (AA) is one of the most important endogenous reducing agents and can participate in a variety of cellular events. In vitro, AA can act as a potent oxidant agent in the presence of free metals, promote modifications in protein structures and form reactive oxygen species during its oxidation. We have observed that AA (above 6 mmol/l) inactivates delta-aminolevulinate dehidratase (delta-ALA-D), a sulfhydryl-containing enzyme and that the inhibitory action was considerably decreased when 3-morpholinepropanesulfonic acid buffer (MOPS - pH: 6.8; 100 mmol/l) was used in the delta-ALA-D activity assay instead of potassium phosphate buffer (PB - pH: 6.8; 100 mmol/l). delta-ALA-D inhibition, probably, is mediated by the oxidation of -SH groups caused by the auto-oxidation of AA promoted by metals or another oxidizing system present in liver supernatants. This hypothesis was confirmed by studying dithiothreitol (DTT - 400 micromol/l) oxidation, as a model of enzyme thiols, where we observed that the mechanism underlying DTT and delta-ALA-D oxidation caused by ascorbate is the same. The difference observed between different buffers may be related to the oxidation of Fe(II) to Fe(III) that was more accentuated in PB than in MOPS buffer. The presence of ethilenediamintetraacetic acid (EDTA - 100 micromol/l) and Fe(III) (5 micromol/l) stimulated DTT oxidation more in PB than in MOPS buffer. Deferroxamine (DF - 100 micromol/l) considerably decreased DTT oxidation. Catalase (0.4 mg/ml) and Superoxide dismutase (SOD - 300 U/ml) had only a modest effect on DTT oxidation. The present results suggest that delta-ALA-D inhibition by AA is mediated primarily by the oxidized form of AA and reactive oxygen species play only a modest role in the process.
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PMID:Oxidation of delta-ALA-D and DTT mediated by ascorbic acid: modulation by buffers depends on free iron. 1607 98