Role of HSP27 and reduced glutathione in modulating malathion-induced apoptosis of human peripheral blood mononuclear cells: ameliorating effect of N-acetylcysteine and curcumin.
Malathion exerts cholinergic effects at high doses. However, a consequence of low dose (non-cholinergic) exposure causes immunotoxicity and oxidative stress. Hence, this study was designed to find out (i) the cytotoxic and apoptotic effects of cholinergic and non-cholinergic doses of malathion using cultured peripheral blood mononuclear cells (PBMCs) and (ii) the role of GSH and HSP27 and (iii) protective effects of N-acetylcysteine (GSH inducer) and curcumin (HSP27 inducer). In low doses, malathion caused mild depletion of GSH, threefold increase in HSP27 level and a range bound cytotoxicity and apoptosis of PBMC. In contrast, cholinergic dose exposures caused severe GSH depletion and exhibited dose dependent cytotoxicity and necrosis without any significant effect on HSP27 levels. Curcumin increased the levels of HSP27 in PBMC only in presence of low doses and not at high doses of malathion. Both NAC and curcumin were able to prevent malathion-mediated apoptosis of PBMC effectively at non-cholinergic doses and at this concentration of malathion, HSP27 induction keeps apoptosis and GSH depletion under control. Also NAC and curcumin may act as potential therapeutic agents to prevent malathion-induced immunotoxicity.
Ahmed
Tanzeel
T
Environmental Biochemistry and Immunology Laboratory, Department of Biochemistry, University College of Medical Sciences and G.T.B. Hospital (University of Delhi), Dilshad Garden, Delhi 110 095, India.
Tripathi
Ashok K
AK
Suke
Sanvidhan G
SG
Kumar
Vivek
V
Ahmed
Rafat S
RS
Das
Shukla
S
Banerjee
Basu Dev
BD
D000111:Acetylcysteine / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008294:Malathion / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010575:Pesticides / Q000633:toxicity*; D020011:Protective Agents / Q000494:pharmacology*; D018675:Toxicity Tests
D016166:Free Radical Scavengers; D055551:HSP27 Heat-Shock Proteins; D010575:Pesticides; D020011:Protective Agents; D005978:Glutathione; D003474:Curcumin; D008294:Malathion; D000111:Acetylcysteine