Effects of butane-2,3-dione thiosemicarbazone oxime on testicular damage induced by cadmium in mice

J Toxicol Sci. 2012;37(5):899-910. doi: 10.2131/jts.37.899.

Abstract

Our group of studies investigated the action of butane-2,3-dione thiosemicarbazone oxime against the testicular damage caused by cadmium chloride (CdCl(2)) in mice. Mice received a single injection of CdCl(2 )(5 mg/kg, intraperitoneally) and, after thirty minutes, the oxime (10 mg/kg, subcutaneously) was administered. Twenty four hours after the last administration, the animals were killed by cervical dislocation and the testes and serum were removed for analysis. The parameters determined were δ-aminolevulinate dehydratase (δ-ALA-D), myeloperoxidase (MPO), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities. The levels of thiobarbituric acid-reactive substances (TBARS), nonprotein thiols (NPSH), ascorbic acid, cadmium and testosterone were also determined. In addition, histological analysis and cytokines quantification (IL-1, IL-6, IL-10, TNF-α and IFN-γ) were performed. Our results demonstrated that the oxime was effective in restoring the inhibition in δ-ALA-D activity induced by CdCl(2). The activation of MPO and increase in IL-1, IL-6, TNF-α and IFN-γ levels induced by CdCl(2) were also reduced by oxime. IL-10, which was reduced by cadmium, was restored by oxime administration. In addition, the oxime was effective in restoring the increase in TBARS levels and the reduction on NPSH levels induced by CdCl(2). Our results demonstrated that oxime was effective in containing the histological alterations induced by CdCl(2). In addition, oxime was able to increase the testosterone levels, reduced by cadmium exposure. In conclusion, the oxime tested was effective in reducing the testicular damage induced by CdCl(2) in mice. The beneficial effects of this oxime are related to its antioxidant and anti-inflammatory action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Cadmium / pharmacokinetics
  • Cadmium / toxicity*
  • Cytokines / blood
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / metabolism
  • Male
  • Mice
  • Oximes / pharmacology
  • Oximes / therapeutic use*
  • Peroxidase / metabolism
  • Porphobilinogen Synthase / metabolism
  • Sulfhydryl Compounds / metabolism
  • Testicular Diseases / chemically induced
  • Testicular Diseases / drug therapy*
  • Testicular Diseases / metabolism
  • Testicular Diseases / pathology
  • Testosterone / blood
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Thiosemicarbazones / pharmacology
  • Thiosemicarbazones / therapeutic use*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Oximes
  • Sulfhydryl Compounds
  • Thiobarbituric Acid Reactive Substances
  • Thiosemicarbazones
  • butane-2,3-dione thiosemicarbazone oxime
  • Cadmium
  • Testosterone
  • Peroxidase
  • Glutathione Peroxidase
  • Glutathione Transferase
  • Porphobilinogen Synthase