Ursodeoxycholic acid attenuates 5‑fluorouracil‑induced mucositis in a rat model

Abstract

Intestinal mucositis is a commonly encountered complication of chemotherapy. However, there are few effective treatments or preventive methods. Ursodeoxycholic acid (UDCA) stabilizes cell membranes, acts as an antioxidant and inhibits apoptosis, thereby exerting cytoprotective effects. The aim of the present study was to examine the ability of UDCA to protecting against chemotherapy-associated mucositis. Sprague-Dawley rats were randomly assigned to five groups: Control, vehicle + 5-fluorouracil (5-FU), 5-FU + UDCA (10 mg/kg/day), 5-FU + UDCA (100 mg/kg/day) and 5-FU + UDCA (500 mg/kg/day). Following randomization, a single dose of 5-FU was injected and varying amounts of UDCA was administered to each group. UDCA was administered orally to rats for 6 days, beginning 1 day prior to 5-FU administration. The rats were sacrificed 1 day following the last UDCA administration and intestinal tissue specimens were prepared for analysis. UDCA administration attenuated body weight loss, decreased inflammatory cytokine levels and curbed intestinal villus damage in the 10 and 100 mg/kg/day groups. When compared with the jejunal villi lengths in the vehicle+5-FU group (212.8±58.0 µm), those in the 5-FU + UDCA (10 mg/kg/day) and 5-FU + UDCA (100 mg/kg/day) groups were significantly greater [331.3±18.0 µm (P=0.001) and 310.0±112.6 µm (P=0.046), respectively]. Tumor necrosis factor-α and interleukin-6 levels were reduced in the 10 and 100 mg/kg/day UDCA groups (P<0.05). UDCA considerably attenuated the elevation in inflammatory cytokines and intestinal villus damage. The results of the study suggest that UDCA may be used as a protective agent against chemotherapy-associated intestinal mucositis.

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

“…Thus, it seems counterintuitive to use chemical chaperones such as TUDCA in cancer research, since their cytoprotective potential would rather benefit in maintaining neoplastic cells instead of eliminating them. Paradoxically, several reports from in-vitro and in-vivo studies inform that TUDCA/UDCA might have some favorable effects in therapy of certain types of cancer [175][176][177][178][179][180][181]. Early studies of the influence of TUDCA on growth of human cholangiocarcinoma Mz-ChA-1 cell line demonstrated that TUDCA suppressed the growth of the Mz-ChA-1 cells due to increased calcium signaling and downstream activation of PKC-α-and MAPK p42/44-dependent pathways [175].…”

“…Taking into consideration the cytoprotective activity of TUDCA/UDCA, it has been used as a co-therapeutic agent helping to deal with the outcomes of standard chemotherapeutic approaches [178]. UDCA when administrated to Sprague-Dawley rats treated with 5-fluorouracil (5-FU) protected animals against chemotherapy-induced intestinal mucositis, which is a common side effect of chemotherapy [178].…”

“…Taking into consideration the cytoprotective activity of TUDCA/UDCA, it has been used as a co-therapeutic agent helping to deal with the outcomes of standard chemotherapeutic approaches [178]. UDCA when administrated to Sprague-Dawley rats treated with 5-fluorouracil (5-FU) protected animals against chemotherapy-induced intestinal mucositis, which is a common side effect of chemotherapy [178]. As such, UDCA administration alleviated 5-FU-induced body weight loss, reduced inflammatory cytokine (TNF-α and IL-6) levels, and attenuated intestinal villus damage, suggesting beneficial effects of chemotherapy-associated mucositis [178].…”

Dipeptidyl-peptidase-4 (DPP-4) inhibitor ameliorates 5-flurouracil induced intestinal mucositis

“…We divided the mice into four groups: the control group, 5-FU group (5-FU), DPP-4 inhibitor and saline group (DPP-4i), and the DPP-4 inhibitor and 5-FU group (DPP-4i + 5-FU). Mucositis was made with a single intraperitoneal injection of 5-FU (400 mg/kg) (JW Pharmaceutical, Seoul, Korea) [10, 11]. Mice were administered a single intraperitoneal injection of 5-FU into the abdomen at day 2.…”

Probiotics, Prebiotics, Synbiotics, and Paraprobiotics as a Therapeutic Alternative for Intestinal Mucositis

“…Mucositis is an inflammation of the gastrointestinal tract (GIT), with symptoms that include diarrhea, abdominal pain, bleeding, fatigue, malnutrition, electrolyte imbalance, and infections, causing complications that may be life threatening (Sonis, 2004;Touchefeu et al, 2014;Kim S. et al, 2018). The cytotoxic effects of 5-FU in the GIT cells are a severe problem for oncological therapeutics, as they decrease the patient's ability to tolerate treatment, affecting the quality of life, directly influencing the success of therapy (Jamali et al, 2018).…”