Ascorbic acid attenuates antineoplastic drug 5-fluorouracil induced gastrointestinal toxicity in rats by modulating the expression of inflammatory mediators.

ABSTRACT

Damage to the mucous membrane is a serious issue associated with chemotherapy. Gastrointestinal (GI) toxicity is complex and multistep process and unregulated production of reactive oxygen species (ROS) and inflammatory mediators play vital role in the development of GI toxicity. In the present study we have investigated the attenuating potential of vitamin C (vit. C) on 5 fluorouracil (5-FU) induced GI toxicity by targeting oxidative stress and inflammatory markers in Sprague Dawley (SD) rats. Rats were gavaged with vit. C (500 mg/kg b. wt.) or vehicle daily (day 1-10) and were given intraperitoneal injection of 5-FU (150 mg/kg b. wt.) or saline (control) on day 8 to induce mucositis. We found that vit. C supplementation attenuated 5-FU induced lipid peroxidation, myeloperoxidase (MPO) activity, activation of NF-kB and expression of COX-2. Histological observations further supported the protective potential of vit. C against 5-FU induced intestinal anomalies such as neutrophil infiltration, loss of cellular integrity, villus and crypt deformities. Thus the biochemical, molecular and histological findings of the present study demonstrate that oxidative stress and inflammation play vital role in 5-FU induced GI toxicity and the inhibitory potential of vit. C is may be due to the modulation of oxidative stress, activation of redox sensitive transcription factor and also its downstream target molecules.