http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
In vitro and in vivo evaluation of the mechanisms of citalopraminduced hepatotoxicity
Elham Ahmadian,Aziz Eftekhari,Javad Khalili Fard,Hossein Babaei,Alireza Mohajjel Nayebi,Daryoush Mohammadnejad,Mohammad Ali Eghbal 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.11
Even though citalopram is commonly used inpsychiatry, there are several reports on its toxic effects. So,the current study was designed to elucidate the mechanismsof cytotoxic effects of in vitro and in vivo citalopramtreatment on liver and the following cytolethal events. Forin vitro experiments, freshly isolated rat hepatocytes wereexposed to citalopram along with/without various agents. To do in vivo studies liver function enzyme assays andhistological examination were performed. In the in vitroexperiments, citalopram (500 lM) exposure demonstratedcell death, a marked elevation in ROS formation, mitochondrialpotential collapse, lysosomal membrane leakiness,glutathione (GSH) depletion and lipid peroxidation. In vivo biochemistry panel assays for liver enzymesfunction (AST, ALT and GGTP) and histological examinationconfirmed citalopram (20 mg/kg)-induced damage. citalopram-induced oxidative stress cytotoxicity markerswere significantly prevented by antioxidants, ROS scavengers,MPT pore sealing agents, endocytosis inhibitors,ATP generators and CYP inhibitors. Either enzymeinduction or GSH depletion were concomitant with augmentedcitalopram-induced damage both in vivo andin vitro which were considerably ameliorated withantioxidants and CYP inhibitors. In conclusion, it is suggestedthat citalopram hepatotoxicity might be a result ofoxidative hazard leading to mitochondrial/lysosomal toxicconnection and disorders in biochemical markers whichwere supported by histomorphological studies.