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.