Mitigative action of monoisoamyl-2,3-dimercaptosuccinate (MiADMS) against cadmium-induced damage in cultured rat normal liver cells

Toxicol In Vitro. 2011 Dec;25(8):1733-9. doi: 10.1016/j.tiv.2011.08.013. Epub 2011 Sep 3.

Abstract

Cadmium is non-essential, carcinogenic and multitarget pollutant in the environment. Monoisoamyl-2,3-dimercaptosuccinate (MiADMS) is an ester of dimercaptosuccinic acid that acts as an antioxidant and chelator. Therefore, the mitigative action of MiADMS on viability, morphology, antioxidative enzymes and cell cycle were studied on rat liver cells treated with cadmium chloride (CdCl2). The cells were treated with 150 μM CdCl2 alone or cotreated with 300 μM MiADMS (concurrently, 2 h or 4 h post-CdCl2 treatment) for 24 h. The viability of cells treated with CdCl2 alone was decreased in comparison to the control cells. Cotreatment with MiADMS resulted in an increase in cell viability in comparison to the CdCl2 alone treated cells. The CdCl2 treatment altered the morphological shape of the cells, while cotreatment with MiADMS restored the shape. Antioxidative enzymes activities were decreased in the cells treated with CdCl2 alone, while MiADMS cotreatment resulted in an increase in enzyme activities. The CdCl2 arrested the cells in S phase of the cell cycle. Cotreatment with MiADMS alleviated cell cycle arrest by shifting to G1 phase. These results clearly show the mitigative action of MiADMS on CdCl2 toxicity and may suggest that MiADMS can be used as an antidote against cadmium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Cadmium / toxicity*
  • Catalase / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Chelating Agents / pharmacology*
  • Environmental Pollutants / toxicity*
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Hepatocytes / drug effects*
  • Hepatocytes / enzymology
  • Hepatocytes / pathology
  • Rats
  • S Phase / drug effects
  • Succimer / analogs & derivatives*
  • Succimer / pharmacology

Substances

  • Antioxidants
  • Chelating Agents
  • Environmental Pollutants
  • Cadmium
  • monoisoamyl-2,3-dimercaptosuccinate
  • Succimer
  • Catalase
  • Glutathione Peroxidase
  • Glutathione Reductase