title: Cellular Preoxygenation Partially Attenuates the Antitumoral Effect of Cisplatin despite Highly Protective Effects on Renal Epithelial Cells.
abstract: Our previous in vitro studies demonstrated that oxygen pretreatment significantly protects human embryonic renal tubular cell against acute cisplatin- (CP-) induced cytotoxicity. The present study was designed to investigate whether this protective effect is associated with decreasing therapeutic effects of cisplatin on malignant cells. For this purpose, cultured human embryonic kidney epithelial-like (AD293), cervical carcinoma epithelial-like (Hela), and ovarian adenocarcinoma epithelial-like (OVCAR-3) cells were subjected to either 2-hour pretreatment with oxygen (≥90%) or normal air and then to a previously determined 50% lethal dose of cisplatin for 24 hours. Cellular viability was evaluated via MTT and Neutral Red assays. Also, activated caspase-3 and Bax/Bcl-2 ratio, as the biochemical markers of cell apoptosis, were determined using immunoblotting. The hyperoxic preexposure protocol significantly protects renal AD293 cells against cisplatin-induced toxicity. Oxygen pretreatment also partially attenuated the cisplatin-induced cytotoxic effects on Hela and OVCAR-3 cells. However, it did not completely protect these cells against the therapeutic cytotoxic effects of cisplatin. In summary, the protective methods for reducing cisplatin nephrotoxic side effects like oxygen pretreatment might be associated with concurrent reduction of the therapeutic cytotoxic effects of cisplatin on malignant cells like cervical carcinoma (Hela) and ovarian adenocarcinoma (OVCAR-3) cells.
authors.affiliation: Razi Herbal Medicines Research Center and Department of Physiology, Lorestan University of Medical Sciences, Khorramabad, Iran.
authors.forename: Bahram
authors.initials: B
authors.lastname: Rasoulian
authors.affiliation: Department of Physiology and Pharmacology, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
authors.forename: Ayat
authors.identifier: 0000-0002-2027-272X
authors.initials: A
authors.lastname: Kaeidi
authors.affiliation: Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rezaei
authors.affiliation: Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Hajializadeh
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects*; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D018496:Hyperoxia / Q000473:pathology; D019194:Ischemic Preconditioning; D007668:Kidney / Q000187:drug effects*; D010100:Oxygen / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D010100:Oxygen