Oxygen radical generation and endosulfan toxicity in Jurkat T-cells.
The mechanism by which endosulfan exposure causes cellular dysfunction in experimental animals and humans is not clear. In the present study, we provide experimental evidence in support of the role of oxidative stress in endosulfan toxicity. Using both cell free system and Jurkat cells as in vitro models, we demonstrate that endosulfan can generate oxygen radicals that is inhibitable by superoxide dismutase (SOD) and glutathione (GSH). In the cell culture model, oxygen radical generation in response to endosulfan was dose- (0-100 microM) and time-dependent (0-12 h). Two-color flowcytometric analysis showed that endosulfan mediated changes in delta psi(m) and generation of superoxide radicals do occur simultaneously in the affected cell population. It was hypothesized that endosulfan exerts a severe oxidative stress in Jurkat cells and this could be prevented or minimized by an antioxidant. To test this hypothesis, GSH was added exogenously and endosulfan toxicity was evaluated by alamarblue assay. In conclusion, our results demonstrate a role for reactive oxygen species (ROS) in endosulfan toxicity and that supplementation of antioxidants such as GSH may be useful in individuals who are at risk to endosulfan toxicity.
Kannan
Krishnaswamy
K
Department of Medicine/Arthritis Center, LSU Health Sciences Center, Shreveport, LA 71130, USA. kkanna@lsuhsc.edu
Jain
Sushil K
SK
D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D004726:Endosulfan / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides / Q000633:toxicity*; D007425:Intracellular Membranes / Q000187:drug effects; D019169:Jurkat Cells / Q000187:drug effects* / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D005978:Glutathione; D004726:Endosulfan