title: Comparative effects of cocaine and cocaethylene on alveolar epithelial type II cells.
abstract: Abuse of cocaine (COC) and alcohol have been among the leading causes of non-prescription drug-related deaths in the USA and are known to cause acute and chronic lung diseases. The co-abuse of COC and alcohol results in the production of an active metabolite, cocaethylene (CE). The effects of COC and its metabolites on the respiratory system have been scarcely studied. This study was aimed at comparing the toxic effects of eqimolar concentration (1 mM) of COC and CE on alveolar epithelial type II cells. This was performed by measuring cell growth, viability, clonogenic activity, cell cycle and reactive oxygen species (ROS) generation. The treatment of CE and COC resulted in a significant inhibition of cell proliferation with the formation of an average of three colonies which measured about 1.74×10(-15) m each and 25 colonies each of about 5.73×10(-15) m, respectively, while untreated cells yielded 31 colonies of 8.75×10(-15) m (p<0.05). The treatments of CE and COC resulted in the reduction of the growth fraction of alveolar epithelial type II cells without significant decrease in viability. In addition, there was an approximately twofold increase in ROS generation as compared to the controls (p<0.05). Therefore, CE-induced inhibition of cellular proliferation may contribute to the pathogenesis of diffuse alveolar damage in co-abusers of COC and alcohol.
authors.affiliation: a Department of Pathology , University of Texas Medical Branch , Galveston , TX , USA.
authors.forename: Eseosa A
authors.initials: EA
authors.lastname: Bazuaye-Ekwuyasi
authors.affiliation: a Department of Pathology , University of Texas Medical Branch , Galveston , TX , USA.
authors.forename: John O
authors.initials: JO
authors.lastname: Ogunbileje
authors.affiliation: a Department of Pathology , University of Texas Medical Branch , Galveston , TX , USA.
authors.forename: Bhupendra S
authors.initials: BS
authors.lastname: Kaphalia
authors.affiliation: a Department of Pathology , University of Texas Medical Branch , Galveston , TX , USA.
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Eltorky
authors.affiliation: a Department of Pathology , University of Texas Medical Branch , Galveston , TX , USA.
authors.forename: Anthony O
authors.initials: AO
authors.lastname: Okorodudu
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003042:Cocaine / Q000031:analogs & derivatives* / Q000633:toxicity*; D003114:Colony-Forming Units Assay; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D006801:Humans; D013287:Illicit Drugs / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D013287:Illicit Drugs; D017382:Reactive Oxygen Species; C066444:cocaethylene; D003042:Cocaine
keywords: Cell proliferation; clonogenic assay; oxidative stress