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

Abstract

<jats:p> 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<jats:sup>−1</jats:sup> body weight (b.wt.)) was given to the animals in group III and group IV. 5-FU (150 mg kg<jats:sup>−1</jats:sup> 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. </jats:p>

Induction of apoptosis and proliferation inhibition of hepatocellular carcinoma by 6-chloro-2-methoxy-N-(phenylmethyl)-9-acridinamine (BA): in vitro and vivo studies

“…However, previous research has shown that 5-FU causes nephrotoxicity [19] and hepatotoxicity [29]. These contradictory results may be due to the higher concentration of 5-FU used in these studies.…”

“…In our study, the physiological function of liver, kidney and lung tissue examined by H&E staining showed no obvious differences among BA (5 and 10 mg/kg), 5-FU (10 mg/kg) and the non-treated control. However, previous research has shown that 5-FU causes nephrotoxicity [ 19 ] and hepatotoxicity [ 29 ]. These contradictory results may be due to the higher concentration of 5-FU used in these studies.…”

“…These contradictory results may be due to the higher concentration of 5-FU used in these studies. 150 mg/kg 5-FU was used to study induced renal toxicity and liver damage [ 19 , 29 ], compared to our concentration of 10 mg/kg. When we compare studies that used the same 5-FU concentration as we did, we draw the same conclusion.…”

Enhanced antitumor efficacy and reduced toxicity of Abnormal Savda Munziq on tumor bearing mice treated with chemotherapy

“…Most of 5-FU were metabolized in the liver, and only about 15% of 5-FU were eliminated from the human body as the original urine. Moreover, Long term application of 5-FU can lead to liver injury [ 26 ]. Alanine transaminase (ALT) and aspartate transaminase (AST) are mainly distributed in liver cells, and their increased levels are consistent with the degree of liver cell damage.…”

Nephroprotective Potential of Alpha Lipoic Acid in 5-Fluorouracil-Induced Toxicity of Wistar Rats

“…This experimental design was as described by Al-Asmari et al 6 Wistar rats were randomly divided into six different groups (n=6 each). The first group received normal saline (1 mL/kg) and used as a negative control.…”