Mitigation of 5-fluorouracil-induced liver damage in rats by vitamin C via targeting redox-sensitive transcription factors.

ABSTRACT

Adverse complications associated with antineoplastic drug-based cancer therapy are the major clinical drawbacks. Oxidative stress and inflammation play a major role in the damage due to cancer therapy. In the current study, we investigated the modulatory effect of vitamin C (Vit. C) on liver toxicity induced by 5-fluorouracil (5-FU) in rats. Animals were divided into four groups. Animals in group I received vehicle. Oral gavage of Vit. C (500 mg kg-1 body weight (b.wt.)) was given to the animals in group III and group IV. 5-FU (150 mg kg-1 b.wt.) was injected intraperitoneally to the animals in group II and group III. Findings of the present study revealed that oral administration of Vit. C significantly ameliorated the level of lipid peroxidation and the activity of myeloperoxidase. Vit. C administration markedly reduced the activation of nuclear factor κB and expression of cyclooxygenase 2, whereas nuclear translocation of nuclear factor erythroid 2-related factor 2 was increased. Hepatic histopathological analyses further supported the protective effect of Vit. C. Findings of the current study demonstrate that the toxic free radicals and inflammatory mediators generated due to chemotherapy play a critical role in 5-FU-induced hepatic damage. Attenuating action of Vit. C may be due to the modulation of redox-sensitive transcription factors and associated target molecules.