title: Genetic overexpressing of GPx-1 attenuates cocaine-induced renal toxicity via induction of anti-apoptotic factors.
abstract: The present study investigates the role of the glutathione peroxidase (GPx)-1 gene in cocaine-induced renal damage in mice. Multiple doses of cocaine increased lipid peroxidation, protein oxidation, and glutathione oxidation in the kidney of the non-transgenic mice (non-TG mice). The enzymatic activities of GPx and glutathione reductase were significantly decreased in non-TG mice, whereas superoxide dismutase was increased in the early phase of cocaine exposure. Treatment with cocaine resulted in significant decreases in expression of Bcl-2 and Bcl-xl in the kidney of non-TG mice, which resulted in significant increases in Bax and cleaved-caspase 3. Consistently, cocaine-induced tubular epithelial vacuolization and focal tubular necrosis were mainly observed in the proximal tubules in the kidneys of non-TG mice. These renal pathologic changes were much less pronounced in GPx-1 TG than in non-TG mice. These results suggest that the GPx-1 gene is a protective factor against nephrotoxicity induced by cocaine via interactive modulations between antioxidant and cell survival signaling processes.
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.
authors: Huynh Nhu
authors: HN
authors: Mai
authors: Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Korea.
authors: Ji Hoon
authors: JH
authors: Jeong
authors: Department of Anatomy and Cell Biology, Medical School, Kangwon National University, Chunchon, Korea.
authors: Dae-Joong
authors: DJ
authors: Kim
authors: Department of Anatomy, College of Medicine, Chung-Ang University, Seoul, Korea.
authors: Yoon Hee
authors: YH
authors: Chung
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.
authors: Eun-Joo
authors: EJ
authors: Shin
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.
authors: Lan Thuy Ty
authors: LT
authors: Nguyen
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.
authors: Yunsung
authors: Y
authors: Nam
authors: Clinical Pharmacy, College of Pharmacy, Kangwon National University, Chunchon, Korea.
authors: Yu Jeung
authors: YJ
authors: Lee
authors: Department of Internal Medicine, Medical School, Kangwon National University, Chunchon, Korea.
authors: Eun-Hee
authors: EH
authors: Cho
authors: Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University, Seoul, Korea.
authors: Seung-Yeol
authors: SY
authors: Nah
authors: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
authors: Choon-Gon
authors: CG
authors: Jang
authors: Department of Animal Science, Cornell University, Ithaca, New York, USA.
authors: Xin Gen
authors: XG
authors: Lei
authors: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.
authors: Hyoung-Chun
authors: HC
authors: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D003042:Cocaine / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics*; D006706:Homeostasis / Q000187:drug effects; D007668:Kidney / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D003404:Creatinine; D005979:Glutathione Peroxidase; D003042:Cocaine; D019803:Glutathione Disulfide; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: GPx-1 overexpressing transgenic mice; cocaine; glutathione; kidney; oxidative stress