Thymoquinone protects against 5-Fluorouracil-induced mucositis by NF-κβ and HIF-1 mechanisms in mice |
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Authors: | Fatemeh Madani Sohrab Kazemi Fatemeh Shirafkan Mandana Lotfi Seyed M. Hosseini Ali A. Moghadamnia |
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Affiliation: | 1. Student Research Committee, Health Research Center, Babol University of Medical Sciences, Babol, Iran;2. Cellular and Molecular Biology Research Center, Health Research Center, Babol University of Medical, Babol University of Medical Sciences, Babol, Iran;3. Department of Pharmacology and Toxicology, Babol University of Medical Sciences, Babol, Iran;4. Department of Veterinary Parasitology, Babol-Branch, Islamic Azad University, Babol, Iran |
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Abstract: | Mucositis 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. |
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Keywords: | 5-Fluorouracil HIF-1 mucositis NF-κB thymoquinone |
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