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

Abstract

IntroductionIntestinal 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 (200 mg/kg) were used to induce intestinal mucositis in adult Swiss male mice. Treatment was provided orally (MFC 3.75, 7.5 and 15 mg/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 15 mg/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 < 0.05).ConclusionsOur data suggest the therapeutic potential of the formulation for treating intestinal mucositis in mice. Supplementary studies are underway searching for the elucidation of mechanisms involved in the protective effects of MFC in order to make this formulation a clinical tool for mucositis treatment.

Mulberry leaf extract fermented withLactobacillus acidophilusA4 ameliorates 5-fluorouracil-induced intestinal mucositis in rats

“…In addition, curcuminoids from the plant Curcuma longa L. have demonstrated protective action against duodenal mucosa damage caused by 5‐FU (dos Santos Filho et al . ). However, there has been limited research exploring the effect of mulberry leaf taken in combination with 5‐FU in normal animals.…”

“…It has been reported that the herbal extract Iberogast â reduced the severity of 5-FU-induced mucositis in rats (Wright et al 2009). In addition, curcuminoids from the plant Curcuma longa L. have demonstrated protective action against duodenal mucosa damage caused by 5-FU (dos Santos Filho et al 2016). However, there has been limited research exploring the effect of mulberry leaf taken in combination with 5-FU in normal animals.…”

“…The antimetabolite 5-FU is one of the most commonly used chemotherapeutic agents in clinical oncology, owing to its cytotoxic effect. 5-FU-induced intestinal mucositis in animal models is commonly used to evaluate the protective effect of novel therapeutic materials (Wright et al 2009;dos Santos Filho et al 2016).…”

Effects of turmeric and curcumin on oral mucositis: A systematic review

“…None of the healthy volunteers experienced toxicity nor reported adverse reactions, indicating that both formulations were biochemical, cytological, and clinically safe (dos Santos Filho, Arantes, et al, 2018). The same research group had already demonstrated the chemoprotective effect of the formulation containing curcuminoids on 5-FU-induced toxicity in HaCaT cells and in 5-FU-induced intestinal mucositis in mice(dos Santos Filho et al, 2016;dos Santos Filho, da Silva, et al, 2018). Similarly,Van't Land et al (2004) investigated the effects of curcumin on intestinal mucositis induced by methotrexate in rats and found that inhibition of NF-kB activation with curcumin was effective throughout the entire gastrointestinal tract.…”

Mucoadhesive formulation containing Curcuma longa L. reduces oral mucositis induced by 5‐fluorouracil in hamsters

“…To overcome this limitation, we developed a mucoadhesive system capable of solubilizing a high amount of curcuminoids. In addition, the mucoadhesive constituent (poloxamer 407) probably improved the interaction of the curcumin with the mucin that covers the mucosa, promoting a prolonged and localized contact between the pharmaceutically active agent and the absorptive tissue (Dos Santos Filho et al, ).…”