title: Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an in vitro study.
abstract: BACKGROUND
  Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approved antiobesity drug which is a potent inhibitor of intestinal lipases.
  
  
  OBJECTIVE
  In the current study, orlistat was evaluated for its genotoxic potential in human lymphocyte cells in vitro and was compared with that of another antiobesity drug sibutramine, presently withdrawn from market due its undesirable health effects. Caffeine intake may be an additional burden in people using anorectic drugs, therefore, further work is needed to be carried out to evaluate the possible effects of caffeine on orlistat-induced DNA damage.
  
  
  METHODS
  Human lymphocytes were exposed to orlistat (250, 500 and 1000 μg/ml), sibutramine (250, 500 and 1000 μg/ml) and caffeine (25, 50, 75, 100, 125 and 150 μg/ml) to assess their genotoxicity by comet assay in vitro. In addition, lymphocytes were co-incubated with caffeine (50, 75 and 100 μg/ml) and a single concentration of orlistat (250 μg/ml).
  
  
  RESULTS
  Orlistat and sibutramine were genotoxic at all concentrations tested, sibutramine being more genotoxic. Caffeine was found to be genotoxic at concentrations 125 μg/ml and above. Co-treatment of orlistat with non-genotoxic concentrations (50, 75 and 100 μg/ml) of caffeine lead to a decrease in DNA damage.
  
  
  CONCLUSIONS
  Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity.
authors.affiliation: a Cell Biology and Genetic Toxicology Laboratory, Centre of Advance Study, Department of Botany, University of Calcutta , Kolkata , India.
authors.forename: Manoswini
authors.initials: M
authors.lastname: Chakrabarti
authors.affiliation: a Cell Biology and Genetic Toxicology Laboratory, Centre of Advance Study, Department of Botany, University of Calcutta , Kolkata , India.
authors.forename: Ilika
authors.initials: I
authors.lastname: Ghosh
authors.affiliation: a Cell Biology and Genetic Toxicology Laboratory, Centre of Advance Study, Department of Botany, University of Calcutta , Kolkata , India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Jana
authors.affiliation: a Cell Biology and Genetic Toxicology Laboratory, Centre of Advance Study, Department of Botany, University of Calcutta , Kolkata , India.
authors.forename: Manosij
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: a Cell Biology and Genetic Toxicology Laboratory, Centre of Advance Study, Department of Botany, University of Calcutta , Kolkata , India.
authors.forename: Anita
authors.initials: A
authors.lastname: Mukherjee
mesh_terms: D000328:Adult; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000633:toxicity*; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D000077403:Orlistat
chemical_list: D019440:Anti-Obesity Agents; D007783:Lactones; D009153:Mutagens; D002110:Caffeine; D000077403:Orlistat
keywords: Caffeine; DNA damage; comet assay; lymphocyte; orlisat; sibutramine