title: Protective effect of amifostine on busulfan induced DNA damage in human hepatoma cells.
abstract: Busulfan is one of the most effective chemotherapeutic agents used for the treatment of chronic myeloid leukemia. However, as a bifunctional alkylating agent, during clinical use several side effects may occur. In addition, several in vivo and in vitro studies of busulfan have shown a range of genotoxic effects including DNA strand break and inhibition of DNA synthesis. Amifostine, an organic thiophosphate compound, has been shown to exert an important cyto-protective effect in many tissues. The aim of this study was to explore whether amifostine protects against busulfan-induced genotoxicity in HepG2 cell line. Our results showed that amifostine reduced the genotoxic effects of busulfan significantly in both type of experiment conditions, as measured via comet assay. Furthermore, amifostine decreased the intracellular ROS generation induced by busulfan and also increased the intracellular GSH levels in HepG2 cells. Altogether, our results suggest a protective action of amifostine against busulfan cytotoxicity and genotoxicity via various pathways. The most protective effect was observed with amifostine when it was administrated 24 h before busulfan treatment.
authors: a Department of Pharmacology and Toxicology Faculty of Pharmacy and Pharmaceutical Sciences , Isfahan University of Medical Sciences , Isfahan , Iran (the Islamic Republic of).
authors: Nasrin
authors: N
authors: Ghassemi-Barghi
authors: a Department of Pharmacology and Toxicology Faculty of Pharmacy and Pharmaceutical Sciences , Isfahan University of Medical Sciences , Isfahan , Iran (the Islamic Republic of).
authors: Mahmoud
authors: M
authors: Etebari
authors: a Department of Pharmacology and Toxicology Faculty of Pharmacy and Pharmaceutical Sciences , Isfahan University of Medical Sciences , Isfahan , Iran (the Islamic Republic of).
authors: Abbas
authors: A
authors: Jafarian-Dehkordi
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D002066:Busulfan / Q000633:toxicity*; D018929:Cell Culture Techniques; D020552:Comet Assay; D019610:Cytoprotection; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016587:Antimutagenic Agents; D018906:Antineoplastic Agents, Alkylating; D017382:Reactive Oxygen Species; D002066:Busulfan; D005978:Glutathione; D004999:Amifostine
keywords: Amifostine; busulfan; comet assay; oxidative stress