Comparative study on the influence of subcutaneous administration of diphenyl and dicholesteroyl diselenides on sulphydryl proteins and antioxidant parameters in mice.
Although in vitro data from our previous studies show that the antioxidant effect and reactions of both diphenyl diselenide (DPDS) and dicholesteroyl diselenide (DCDS) towards thiol-containing proteins differ considerably, the present study sought to evaluate the interaction of both organodiselenides with thiol-containing proteins in vivo. Mice were injected subcutaneously with DPDS or DCDS previously dissolved in soya bean oil at doses of 0.5 mmol kg⁻¹ body weight for four consecutive days. The activities of delta aminolevulinic acid dehydratase (ALA-D), Na+/K+-ATPase, and isoforms of lactate dehydrogenase (LDH) and catalase were investigated. In addition, the antioxidant status of the mice was determined by measuring the levels of glutathione (GSH), vitamin C (Vit C) and thiobarbituric acid reactive substances. The results show that both diselenides significantly increased the levels of GSH and Vit C but did not markedly alter other antioxidant indices. With respect to the thiol-containing enzymes that were evaluated, DPDS and not DCDS caused a marked reduction in the activities of hepatic ALA-D; however, both diselenides inhibited all isoforms of LDH evaluated. In addition, the activities of cerebral Na+/K+-ATPase were not markedly inhibited by both diselenides, suggesting that this cerebral enzyme may not be a molecular target of organodiselenides toxicity. Taken together, the pharmacological and toxicological chemistry of organoselenium compounds is complex and multifactorial and is dependent on delicate equations which include vehicle solution, animal species and mode of delivery.
Kade
I J
IJ
Postgraduate Programme in Biochemical Toxicology, Centre for Natural and Exact Sciences, Federal University of Santa Maria, CEP 97105-900, Camobi, Santa Maria, RS, Brazil. ijkade@yahoo.com
Rocha
J B T
JB
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000032:analysis / Q000378:metabolism; D001555:Benzene Derivatives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002374:Catalase / Q000378:metabolism; D002784:Cholesterol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D007279:Injections, Subcutaneous; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism
D000975:Antioxidants; D001555:Benzene Derivatives; D007527:Isoenzymes; D016566:Organoselenium Compounds; D011506:Proteins; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; C539240:dicholesteroyl diselenide; C061132:diphenyldiselenide; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D000623:Porphobilinogen Synthase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D001205:Ascorbic Acid