Curcuminoids from Curcuma longaL. reduced intestinal mucositis induced by 5-fluorouracil in mice: Bioadhesive, proliferative, anti-inflammatory and antioxidant effects

AbstractIntroductionIntestinal mucositis is a frequent limiting factor in anticancer therapy and there is currently no broadly effective treatment targeted to cure this side effect.ObjectiveThis study aimed to evaluate the effects of a mucoadhesive formulation containing curcuminoids (MFC) from Curcuma longa L. on the pathogenesis of 5-fluorouracil (5-FU)-induced intestinal mucositis.MethodsThree intraperitoneal 5-FU injections (200mg/kg) were used to induce intestinal mucositis in adult Swiss male mice. Treatment was provided orally (MFC 3.75, 7.5 and 15mg/kg), thirty minutes before 5-FU injections, daily until euthanasia. Duodenal samples were collected to perform morphometric and histopathological analysis, to investigate the expression of Ki-67, p53, Bax and Bcl-2 by immunohistochemistry, to evaluate neutrophil activity myeloperoxidase (MPO)-mediated and oxidative stress by malondialdehyde (MDA) determination. Mice body weight was assessed as well.ResultsAs expected, 5-FU induced a significant weight loss (∼17%, P<0.001), shortening in villi height (∼55.4%) and crypts depth (∼47%), and increased (∼64%) the histological severity score when compared to other groups (P<0.05). These pathological changes were markedly alleviated by the three MFC treatment doses (P<0.05), in special with the dose MFC 15mg/kg. This dose also stimulated cell proliferation by ∼90% in the epithelial cells lining from villi and crypts (P<0.05), reduced MPO levels and MDA formation by 60% and 44%, respectively (P