Diadzein ameliorates 5-fluorouracil-induced intestinal mucositis by suppressing oxidative stress and inflammatory mediators in rodents.

Affiliation

College of Pharmacy, Seoul National University, Seoul, South Korea. Electronic address: [Email]

Abstract

5-Fluorouracil (5-FU) is one of the most commonly prescribed anti-cancer agent. However, its use is associated with several debilitating adverse effects such as intestinal mucositis (IM) and myelosuppression. Oxidative stress and inflammation are major contributors in the development of mucositis. Diadzein is known for its potent anti-inflammatory and anti-oxidative activities from decades. The present study focused on investigating the effects of diadzein on intestinal mucositis induced by 5-FU by mainly focusing on oxidative stress and inflammatory markers in mice. Mucositis was induced in mice by administration of 5-FU (50 mg/kg, i.p.), once daily for three days and diadzein (1, 5, 10 mg/kg) was administered once daily for seven days. Diadzein pretreatment was found to reduce the severity of mucosal injury in a dose-dependent manner. Diadzein significantly reversed weight loss, relieved diarrhea, and improved histopathological deformities associated with inflammation. Moreover, diadzein remarkably improved the intestinal wall histopathology by reducing inflammatory mediators infiltration and prevented suppression of antioxidants (glutathione, glutathione sulfo-transferase, and catalase) by 5-FU administration. Furthermore, nitrite production in intestinal tissue was reduced by diadzein consistent with the observed modulation of inflammatory markers. Additionally, diadzein also improved the amended microflora profile, by reducing the number of pathogenic bacteria and increasing the abundance of probiotics. Taken together, the behavioral, biochemical and histological outcomes of the present study demonstrates that diadzein has significant anti-mucositis properties in 5-FU induced mucositis model, and the attenuative potential of diadzein might be due to inhibition of oxidative stress and inflammatory mediators.

Keywords

5-Flourouracil,Diadzein,Diarrhea,Histopathology,Mucositis,