Hesperetin alleviates DMH induced toxicity via suppressing oxidative stress and inflammation in the colon of Wistar rats.

Abstract

1,2-Dimethylhydrazine (DMH), a colon-specific environmental toxicant is one among the carcinogen responsible for the cause of colon cancer. The present study was designed to evaluate the protective effect of Hesperetin (HST) against colon toxicity induced by DMH in Wistar rats. HST, a flavonoid widely found in citrus fruits possesses several biological activities including anti-microbial, anti-oxidant properties among others. A single dose of DMH (40 mg/kg body weight) was administered subcutaneously on 1st day for induction of colon toxicity followed by oral treatment with HST at a dose of 20 mg/kg bodyweight for 14 consecutive days. DMH administration leads to excessive ROS generation, resulting in an imbalance in redox homeostasis and causing membrane lipid peroxidation, which is also partly due to the decrease in the level of tissue antioxidant machinery. Our result showed HST significantly ameliorates DMH-induced lipid peroxidation and also substantially increases the activity/level of various anti-oxidant proteins (GR, GPx, GST, GSH, and SOD). HST was also found to reduce the expression of inflammatory proteins (TNF-α, IL-6, i-NOS, COX-2, NF-kB-p65), goblet cell disintegration as well as mucin depletion (sulfo and sialomucin) in the colon that was found to be elevated upon administration of DMH. Our histological results further provide confirmation of the protective role of HST against DMH-induced pathological alterations. The results of the present study demonstrate supplementation of HST is beneficial in ameliorating DMH-induced toxicity by suppressing oxidative stress, inflammation, goblet cell disintegration as well mucin depletion in the colon of Wistar rats.