Alleviation of 5-fluorouracil-induced intestinal mucositis in rats by vitamin E via targeting oxidative stress and inflammatory markers.
BackgroundIntestinal mucositis is a major concern related with cancer therapy. It is well established that overproduction of reactive oxygen species and inflammatory mediators plays vital role in the pathogenesis of mucositis. The aim of the study was to investigate the modulatory effect of vitamin E (vit. E) on 5-fluorouracil (5-FU)-induced intestinal mucositis by targeting oxidative stress and inflammatory markers in rats. MethodsRats were randomly divided into four groups of six animals each. All four-group animals received normal standard diet and water throughout the experimental period which last up to 10 days. Rats were gavaged with vit. E (300 mg/kg b. wt.) daily for 10 days (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. Results We found that vit. E supplementation ameliorated 5-FU-induced lipid peroxidation, myeloperoxidase activity, activation of nuclear factor κB, expression of cyclooxygenase-2, inducible nitric oxide synthase and mucin depletion. Vit. E administration also attenuated 5-FU-induced histological anomalies such as neutrophil infiltration, loss of cellular integrity, villus and crypt deformities. ConclusionsFindings of the study suggest that vit. E inhibits 5-FU-induced mucositis via modulation of oxidative stress, activation of redox sensitive transcription factor and its downstream targets.
Abdulrahman Khazim
AK
Al-Asmari
Abdul Quaiyoom
AQ
Khan
Sarah A
SA
Al-Asmari
Abdulqadir
A
Al-Rawi
Saud
S
Al-Omani
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005472:Fluorouracil; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009077:Mucins / Q000378:metabolism; D052016:Mucositis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015415:Biomarkers; D009077:Mucins; D016328:NF-kappa B; D014810:Vitamin E; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D005472:Fluorouracil