title: Tolerance of ARPE 19 cells to organophosphorus pesticide chlorpyrifos is limited to concentration and time of exposure.
abstract: Age related macular degeneration is a blinding disease common in elder adults. The prevalence of age related macular degeneration has been found to be 1.8% in the Indian population. Organophosphates are widely used insecticides with well documented neurological effects, and the persistent nature of these compounds in the body results in long term health effects. Farmers exposed to organophosphorus pesticides in USA had an earlier onset of age related macular degeneration when compared to unexposed controls. A recent study found significant levels of an organophosphate, termed chlorpyrifos, in the blood samples of Indian farmers. Therefore, in understanding the link between age related macular degeneration and chlorpyrifos, the need for investigation is important. Our data show that ARPE-19 (retinal pigment epithelial cells) exhibit a cytoprotective response to chlorpyrifos as measured by viability, mitochondrial membrane potential, superoxide dismutase activity, and increased levels of glutathione peroxidase and reduced glutathione, after 24 h exposure to chlorpyrifos. However, this cytoprotective response was absent in ARPE-19 cells exposed to the same range of concentrations of chlorpyrifos for 48 h. These results have physiological significance, since HPLC analysis showed that effects of chlorpyrifos were mediated through its entry into ARPE-19 cells. HPLC analysis also showed that chlorpyrifos remained stable, as we recovered up to 80% of the chlorpyrifos added to 6 different ocular tissues.
authors.affiliation: RS Mehta Jain Department of Biochemistry and Cell biology, No. 41, College road, Chennai 600041, India.
authors.forename: Narayanan
authors.initials: N
authors.lastname: Gomathy
authors.affiliation: RS Mehta Jain Department of Biochemistry and Cell biology, No. 41, College road, Chennai 600041, India.
authors.forename: Venil N
authors.initials: VN
authors.lastname: Sumantran
authors.affiliation: RS Mehta Jain Department of Biochemistry and Cell biology, No. 41, College road, Chennai 600041, India.
authors.forename: A
authors.initials: A
authors.lastname: Shabna
authors.affiliation: RS Mehta Jain Department of Biochemistry and Cell biology, No. 41, College road, Chennai 600041, India. Electronic address: drkns@snmail.org.
authors.forename: K N
authors.initials: KN
authors.lastname: Sulochana
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004390:Chlorpyrifos / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010575:Pesticides / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D010575:Pesticides; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D004390:Chlorpyrifos
keywords: AMD; Chlorpyrifos; HPLC; Oxidative stress