title: Hepatotoxicity and proteomic mechanism of Di-n-butyl-di-(4-chlorobenzohydroxamato)tin(IV) (DBDCT) in vivo.
abstract: Di-n-butyl-di-(4-chlorobenzohydroxamato)tin(IV) (DBDCT) is an anti-tumour organotin(IV) compound with hepatotoxicity. To investigate the hepatotoxicity and mechanisms of DBDCT in vivo, proteomic technology 2D gel combined with MALDI-TOF-MS was used in our research. Results indicated that DBDCT increased AST, AKP and ACP activities and decreased ALT activity. Further, sporadic eosinophilic changes and nuclear pyknosis were visible in hepatic pathological observation. Proteomic analysis showed that twenty-two proteins involved in amino acid, nucleic acid, carbohydrate and lipid metabolism, stress response, multicellular organism development and cell apoptosis were differentially expressed and identified. Notably, a considerable amount of the altered proteins, such as OAT, HPPD, M2GD, GSTM2, Glud1, GSTa, HS90β and PDIA3 participated in multi-metabolic pathways and oxidative stress reactions. Our findings indicated that the inhibition of enzyme activity and oxidative stress were the major mechanisms by which DBDCT induced hepatotoxicity, and the altered proteins could be potential drug targets for the further design of new type of organic tin with high activity and low toxicology.
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Jie-Ran
authors.initials: JR
authors.lastname: Luo
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Yun-Lan
authors.initials: YL
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ge
authors.affiliation: School of Pharmaceutical Science, Shanxi Medical University, Taiyuan 030001, PR China; Shanxi University of Traditional Chinese Medicine, Taiyuan 030024, PR China. Electronic address: sxlqs2012@163.com.
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D009947:Organotin Compounds / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D009947:Organotin Compounds; D020543:Proteome; C542282:dibutyldi(4-chlorobenzohydroxamato)tin(IV)
keywords: Di-n-butyl-di-(4-chlorobenzohydroxamato)tin(IV) (DBDCT); Hepatotoxicity; Mechanism; Proteomics