Immunosuppression and oxidative stress induced by subchronic exposure to carbosulfan in rat spleen: immunomodulatory and antioxidant role of N-acetylcysteine

Toxicol Mech Methods. 2014 Sep;24(6):417-27. doi: 10.3109/15376516.2014.928764. Epub 2014 Aug 4.


The present study was designed to determine the immunosuppressive effects of carbosulfan (CB) and their relationship with an increased formation of reactive oxygen species in rat. Further, we aimed to evaluate the protective effects of N-acetyl-cysteine (NAC) against immunopathological changes induced by CB. Carbosulfan (25 mg/kg) and NAC (2 g/l) were given daily to rats during 30 days, via oral gavage and drinking water, respectively. Cell-mediated immune function, cytokines production, biomarkers of cell redox state maintenance, lipid peroxidation and the activities of antioxidant enzymes were measured in the spleen. Our data showed an increase in WBC percent (28.42%), a reduction in spleen CD8 T-lymphocytes (-85.63%) and a decrease in immunosuppressive cytokines production such as INF-gamma and IL-4. There was a switch from Th1-type to Th2-type cytokines with an unbalance toward anti-inflammatory cytokines. Moreover, a significant decrease in reduced glutathione (-71.68%) and total thiols (-39.81%) levels were observed in treated rats. Conversely, malondialdehyde level in spleen was increased (-42.3%), while glutathione-S-transferase, glutathione peroxidase, superoxide dismutase and catalase activities were depleted. Our results suggest that subchronic CB administration affects cellular enzyme and non-enzyme-mediated antioxidant defense systems and promotes immunotoxicity in rat. On the other hand, our data showed protective effects of NAC. Indeed, there was a recovery of oxidative stress markers and cytokines production. The use of NAC, in our study, as a therapeutic agent showed interesting results against CB toxicity.

Keywords: Carbosulfan; N-acetylcysteine; immunotoxicity; oxidative stress; spleen.

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / pharmacology*
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Carbamates / administration & dosage*
  • Carbamates / toxicity*
  • Drug Administration Schedule
  • Immunomodulation / drug effects*
  • Lipid Peroxidation
  • Male
  • Oxidative Stress / drug effects*
  • Pesticides / toxicity
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Spleen / drug effects*


  • Antioxidants
  • Carbamates
  • Pesticides
  • carbosulfan
  • Acetylcysteine