Thymoquinone protects against 5‐Fluorouracil‐induced mucositis by NF‐κβ and HIF‐1 mechanisms in mice

Abstract

AbstractMucositis is among the most common side effects of 5‐Fluorouracil (5‐FU) and other cancer therapeutic drugs. Thymoquinone (TQ), a bioactive constituent extracted from Nigella sativa, has antioxidant and anti‐inflammatory properties and can modify acute gastrointestinal injury. To investigate the effects of TQ on mucositis induced by 5‐FU, studied animals were divided into four groups: control, 5‐FU unit dose (300 mg/kg) to cause oral and intestinal mucositis (OM and IM), TQ (2.5 mg/kg) and TQ (2.5 mg/kg) plus 5‐FU. Due to The molecular mechanisms, it was confirmed that the expression of NF‐κβ and HIF‐1 increases in OM. The serum levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), as well as pathological parameters, were assessed. Based on our results, the nuclear factor‐kappa β gene expression in the tongue was downregulated significantly in the 5‐FU + TQ compared to the 5‐FU. TQ treatment can diminish MDA, and a reduction in oxidative stress was shown. TQ could also reduce the severity of tissue destruction and damaging effects induced by 5‐FU on the tongue and intestine. We also observed lower villus length and width in the intestine of the 5‐FU group compared to the control group. According to our research's pathological, biochemical, and molecular results, treatment with TQ as an anti‐inflammatory and antioxidant compound may be the potential to improve and treat 5‐FU‐induced OM and IM, and TQ could be used against cancer treatment drugs and exhibit fewer adverse effects.