Genotoxicity of chloroquine in rat liver cells: protective role of free radical scavengers.
The genotoxic effect of chloroquine (CQ), a 4-aminoquinoline antimalarial drug was investigated in rat liver cells using the alkaline comet assay. Chloroquine (0-1000 micromol/L) significantly increased DNA strand breaks of rat liver cells dose-dependently. Rat liver cells exposed to CQ (100-500 micromol/L) and treated with endonuclease III and formamidopyrimidine-DNA glycosylase, the bacterial DNA repair enzymes that recognize oxidized pyrimidine and purine, respectively, showed greater DNA damage than those not treated with the enzymes, providing evidence that CQ induced oxidation of purines and pyrimidines. Treatment of cells with 5 mmol/L N-acetylcysteine, an intracellular reactive oxygen species (ROS) scavenger, and 100 micromol/L and 250 micromol/L deferoxamine, an established iron chelator, significantly decreased the CQ-induced strand breaks and base oxidation, respectively. Similarly, the formation of DNA strand breaks and oxidized bases was prevented by vitamin C (10 micromol/L) (a water-soluble antioxidant), quercetin (50 micromol/L) (an antioxidant flavonoid), and kolaviron (30 micromol/L and 90 micromol/L) (an antioxidant and a liver hepatoprotective phytochemical). The results indicate that the genotoxicity of CQ in rat liver cells might involve ROS and that free radical scavengers may elicit protective effects in these cells.
Farombi
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Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria. olatunde_farombi@yahoo.com
D000818:Animals; D002478:Cells, Cultured; D002738:Chloroquine / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects*; D018384:Oxidative Stress; D051381:Rats
D016166:Free Radical Scavengers; D002738:Chloroquine