The protective effects of thiol-containing compounds on mercuric chloride-induced acute inhibition of enzymes from mouse kidney.
The inhibitory effect of mercuric chloride on mouse kidney enzymes and the treatment of this inhibition with some thiol-containing compounds, e.g., dithiothreitol (DTT), dimercaptosuccinic acid (DMS) and D-penicillamine (Pen) was examined. To produce a significant inhibition of renal enzymes in vivo, it was necessary to administer 5 mg Hg/kg/day, s.c., once daily for 3 doses, and to sacrifice the animals 1 day after the last injection. With this Hg dose, microsomal Mg2+-Na+-K+-ATPase, mitochondrial Mg2+-HCO-3-ATPase and supernatant carbonic anhydrase activities decreased to about 30%, 70% and 60% of normal values, respectively. Combined administration of DTT (5-20 mg/kg, i.p.) and DMS (5-20 mg/kg, i.p.) with HgCl2 restored the enzyme activities to near normal or normal levels in parallel to the administered doses. The effect of Pen was slightly less than that of the above 2 compounds. This may be due to the number of thiol radicals, as Pen is a monothiol and the other 2 compounds are dithiol compounds. Since the toxicity of DMS is very low compared with DTT, DMS may be more suitable for the treatment of mercury poisoning.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000931:Antidotes; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use; D004229:Dithiothreitol / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008627:Mercuric Chloride; D008628:Mercury / Q000037:antagonists & inhibitors; D008630:Mercury Poisoning; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D010396:Penicillamine / Q000627:therapeutic use*; D004113:Succimer / Q000627:therapeutic use*; D013438:Sulfhydryl Compounds / Q000627:therapeutic use*
D000931:Antidotes; D002257:Carbonic Anhydrase Inhibitors; D013438:Sulfhydryl Compounds; D008627:Mercuric Chloride; D004113:Succimer; D000251:Adenosine Triphosphatases; D008628:Mercury; D010396:Penicillamine; D004229:Dithiothreitol