Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

AIM To investigate the effects of orally gavaged aqueous rhubarb extract(RE) on 5-fluorouracil(5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats(n = 8/group) were gavaged daily(1 mL) with water, high-dose RE(HDR; 200 mg/kg) or low-dose RE(LDR; 20mg/kg) for eight days. Intestinal mucositis was induced(day 5) with 5-FU(150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase(MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS B o d y w e i g h t w a s s i g n i f i c a n t l y r e d u c e d i n r a t s administered 5-FU compared to healthy controls(P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels(≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity(by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness(by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats(19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis.CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal inflammation, manifesting from 5-FU-induced intestinal mucositis.

Effects of commercially produced almond by-products on chemotherapy-induced mucositis in rats

AIM To determine if almond extracts reduce the severity of chemotherapy-induced mucositis as determined through biochemical,histological and behavioural markers.METHODS Intestinal mucositis is a debilitating condition characterized by inflammation and ulceration of the gastrointestinal mucosa experienced by cancer patients undergoing chemotherapy.Certain bioactive plant products have shown promise in accelerating mucosal repair and alleviating clinical symptoms.This study evaluated almond extracts for their potential to reduce the severity of chemotherapy-induced mucositis in Dark Agouti rats.Female Dark Agouti rats were gavaged(days 3-11) with either PBS,almond hull or almond blanched water extract at two doses,and were injected intraperitoneally with 5-fluorouracil(5-FU-150 mg/kg) or saline on day 9 to induce mucositis.Burrowing behavior,histological parameters and myeloperoxidase activity were assessed.RESULTS Bodyweight was significantly reduced in rats that received 5-FU compared to saline-treated controls(P < 0.05).Rats administered 5-FU significantly increased jejunal and ileal MPO levels(1048%; P < 0.001 and 409%; P < 0.001),compared to healthy controls.Almond hull extract caused a pro-inflammatory response in rats with mucositis as evidenced by increased myeloperoxidase activity in the jejunum when compared to 5-FU alone(rise 50%,1088 ± 96 U/g vs 723 ± 135 U/g,P = 0.02).Other extractrelated effects on inflammatory activity were minimal.5-FU significantly increased histological severity score compared to healthy controls confirming the presence of mucositis(median of 9.75 vs 0; P < 0.001).The extracts had no ameliorating effect on histological severity score in the jejunum or ileum.Burrowing behavior was significantly reduced in all chemotherapy-treated groups(P = 0.001).The extracts failed to normalize burrowing activity to baseline levels.CONCLUSION Almond extracts at these dosages offer little beneficial effect on mucositis severity.Burrowing provides a novel measure of affective state in studies of chemotherapyinduced mucositis.