Inhibitory effect of ebselen on lactate dehydrogenase activity from mammals: a comparative study with diphenyl diselenide and diphenyl ditelluride.
Ebselen is a seleno compound whose antioxidant properties have been attributed to its thiol-peroxidase and thioredoxin-like activity. However, the excessive oxidation of thiols can be potentially toxic. Thus, this work investigated whether lactate dehydrogenase (LDH) can be a possible in vitro target to the toxicity of ebselen, in comparison with diphenyl diselenide [(PhSe)(2)] and diphenyl ditelluride [(PhTe)(2)]. Ebselen was the most potent inhibitor of LDH. A maximal inhibitory effect was obtained at 2 μM to LDH purified and at 20 μM to LDH from heart and liver homogenates. Moreover, (PhSe)(2), followed by (PhTe)(2), also presented a significant inhibitory effect on LDH activity. DL-dithiothreitol (DTT) was able to revert the inhibition of LDH induced by all compounds tested, confirming the involvement of essential thiol groups on LDH inhibition by organochalcogens. In conclusion, our results show that liver and heart LDH may be a possible target for the toxicity of organochalcogens at relative low concentrations. Our results also indicate that the use of LDH, as a marker of cell viability, may be biased by a direct inhibitory effect of ebselen or other chalcogenides on LDH, resulting in false protection in an in vitro system.
Programa de Pós-Graduação em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, Brasil.
Thiago H
TH
Lugokenski
Liz G
LG
Müller
Paulo S
PS
Taube
João B T
JB
Rocha
Maria E
ME
Pereira
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000633:toxicity*; D001393:Azoles / Q000737:chemistry / Q000633:toxicity*; D001555:Benzene Derivatives / Q000737:chemistry / Q000633:toxicity*; D015415:Biomarkers / Q000032:analysis; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D054833:Isoindoles; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D015394:Molecular Structure; D009206:Myocardium / Q000201:enzymology; D009942:Organometallic Compounds / Q000737:chemistry / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000975:Antioxidants; D001393:Azoles; D001555:Benzene Derivatives; D015415:Biomarkers; D054833:Isoindoles; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; D013438:Sulfhydryl Compounds; C434247:diphenylditelluride; C061132:diphenyldiselenide; C042986:ebselen; D007770:L-Lactate Dehydrogenase; D004229:Dithiothreitol