title: A Schiff base derivative for effective treatment of diethylnitrosamine-induced liver cancer in vivo.
abstract: Hepatocellular carcinoma is one of the most prevalent cancers, with a high morbidity rate, even in developed countries. In the present study, the curative effect of the Schiff base (SB) heterodinuclear copper(II)Mn(II) complex on diethylnitrosamine (DEN)-induced liver carcinoma was investigated. Hepatocarcinoma was initiated by an injection of DEN and promoted by phenobarbital (0.05%) in the diet. In addition, the potential nephrotoxicity of SB was evaluated in a cisplatin-induced nephrotoxicity model. Rats were administered the SB complex (1 and 2 mg/kg body weight/day) for 24 weeks, and cancer progression was investigated by macroscopic, histopathological, and western blot examinations. The administration of SB decreased the incidence and the number of hepatic nodules in a dose-dependent manner by regulating inflammation response and the apoptotic pathway. Western blot analyses from the livers of rats treated with SB after DEN induction showed significantly enhanced Bax and caspase-3 levels, with a marked decrease in the levels of Bcl-2, NF-κB p65 and cyclooxygenase (COX)-2. Results from the nephrotoxicity study showed that, whereas cisplatin increased serum urea nitrogen and creatinine levels, no increase in serum biochemical parameters was detected in SB-treated animals. Moreover, protein levels of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 were lower, whereas nuclear factor-κB (NF-κB p65) and activator protein-1 levels were higher in the kidneys of cisplatin-treated animals compared with that of the SB groups. Therefore, the SB complex could be an alternative chemotherapeutic option for liver cancer treatment once its safety in clinical applications has been examined.
authors.affiliation: aDepartment of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul bDepartment of Pharmaceutical Toxicology, University of Inonu, Malatya cDepartment of Chemistry, Faculty of Sciences and Arts, Süleyman Demirel University, Isparta dDepartment of Animal Nutrition, Faculty of Veterinary Medicine eDepartment of Biology, Faculty of Science fDepartment of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey.
authors.forename: Selami
authors.initials: S
authors.lastname: Demirci
authors.forename: Ayşegül
authors.initials: A
authors.lastname: Doğan
authors.forename: Neşe
authors.initials: N
authors.lastname: Başak
authors.forename: Dilek
authors.initials: D
authors.lastname: Telci
authors.forename: Bülent
authors.initials: B
authors.lastname: Dede
authors.forename: Cemal
authors.initials: C
authors.lastname: Orhan
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tuzcu
authors.forename: Kazm
authors.initials: K
authors.lastname: Şahin
authors.forename: Nurhan
authors.initials: N
authors.lastname: Şahin
authors.forename: İbrahim Hanifi
authors.initials: İH
authors.lastname: Özercan
authors.forename: Fikrettin
authors.initials: F
authors.lastname: Şahin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D056831:Coordination Complexes / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D003300:Copper; D004052:Diethylnitrosamine; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008345:Manganese; D017208:Rats, Wistar; D012545:Schiff Bases / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012545:Schiff Bases; D004052:Diethylnitrosamine; D008345:Manganese; D003300:Copper; D002945:Cisplatin