Effect of trolox and quercetin on sulfur mustard-induced cytotoxicity in human peripheral blood lymphocytes

Objective: To evaluate the protective activity of antioxidants, viz. trolox and quercetin, against sulfur mustard (SM)-induced cytotoxicity. Materials and Methods: Cytotoxicity of various concentrations (20–640 μM) of SM, in the Division of Pharmacology presence or absence of 10 μM trolox or quercetin (-0.5, 0, or +0.5 h) was determined in and Toxicology, Defence Research and Development human peripheral blood lymphocytes after 6-h exposure. Cell viability was measured by Establishment, Jhansi Road, Trypan blue dye exclusion (TBDE). Further, a cytotoxic concentration of SM (80 μM) was Gwalior-474002, Madhya challenged by the two antidotes (-0.5 h) and cell viability was measured by TBDE and leakage Pradesh, India. of intracellular lactate dehydrogenase (LDH). Mitochondrial integrity and peroxide levels were measured by 3-4,5-dimethyl thiazol-Z-yl)-2,5-diphenyltetrazolium bromide and 2’,7’Received: 23.7.2005 dichlorofluoroscin diacetate assay, respectively. Morphological changes of cells exposed to Revised: 30.9.2005 320 μM SM (with or without antidotes) were also visualized under light microscope. Accepted: 16.12.2005 Results: On the basis of TBDE, SM caused cell death of approximately 50% at 80 μM and 100% at 640 μM, respectively. Pretreatment of trolox conferred significant protection comCorrespondence to: R. Bhattacharya pared with quercetin. Also, pretreatment of trolox significantly reduced cell death and LDH E-mail: leakage caused by 80 μM SM but did not prevent the loss of mitochondrial integrity. Trolox [email protected] significantly reduced the levels of peroxides generated by SM. The better protection offered by trolox was evidenced in cell morphology studies too. Conclusion: Pretreatment (-0.5 h) of trolox afforded significant protection against SM-in­ duced cytotoxicity in human lymphocytes. The protection was related to the antioxidant property of trolox, a water soluble analog of α-tocopherol.