title: DMPS reverts morphologic and mitochondrial damage in OK cells exposed to toxic concentrations of HgCl2.
abstract: Mercuric chloride (HgCl(2)) is a highly toxic compound, which can cause nephrotoxic damage. In the present study effects of HgCl(2) on mitochondria integrity and energy metabolism, as well as antidotal effects of 2,3-dimercaptopropane-1-sulfonate (DMPS) were investigated in the opossum kidney derived cell line (OK). OK cell monolayers were incubated during 0, 1, 3, 6, and 9 h in serum-free culture medium containing 15 microM HgCl(2), either in the absence or in the presence of 60 microM DMPS in a 1:4 ratio. Intracellular ATP content, MTT reduction, and HSP70/HSP90 induction were studied; confocal, transmission electron microscopy, and light microscopy studies were also performed. For confocal analysis, a mitochondrial selective probe (MitoTracker Red CMXH2Ros) was used. Antioxidant activity of DMPS was also studied by the scavenging of the free radical 2, 2-diphenyl-1-picrylhydrazyl (DPPH) technique. A decrease of ATP content, an impaired ability to reduce tetrazolium, and dramatic changes on cellular and mitochondrial morphology, and energetic levels were found after either 6 or 9 h of HgCl(2) exposure. Increased expression of HSP90 and HSP70 were also seen. When OK cells were co-incubated with HgCl(2) and DMPS, cellular morphology, viability, intracellular ATP, and mitochondrial membrane potential were partially restored; a protective effect on mitochondrial morphology was also seen. DMPS also showed potent antioxidant activity in vitro. Mitochondrial protection could be the cellular mechanism mediated by DMPS in OK cells exposed to a toxic concentration of HgCl(2).
authors.affiliation: División de Biología Celular y Molecular Centro de Investigación Biomédica del Noreste. IMSS. Administración de Correos No. 4., Apartado Postal 020, Colonia Independencia, Monterrey, NL, CP 64720, México. pilarcarranza@cibinmty.net
authors.forename: Pilar
authors.initials: P
authors.lastname: Carranza-Rosales
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Guzmán-Delgado
authors.forename: Delia E
authors.initials: DE
authors.lastname: Cruz-Vega
authors.forename: Isaías
authors.initials: I
authors.lastname: Balderas-Rentería
authors.forename: A Jay
authors.initials: AJ
authors.lastname: Gandolfi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008627:Mercuric Chloride / Q000633:toxicity*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009893:Opossums; D014494:Unithiol / Q000494:pharmacology*
chemical_list: D000931:Antidotes; D000975:Antioxidants; D002614:Chelating Agents; D014494:Unithiol; D008627:Mercuric Chloride; D000255:Adenosine Triphosphate