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Rhein ameliorates lipopolysaccharide-induced intestinal barrier injury via modulation of Nrf2 and MAPKs

Zhuang, Shen, Zhong, Jia, Bian, Yifei, Fan, Yingsai, Chen, Qiyan, Liu, Ping, Liu, Zhongjie
Life sciences 2019 v.216 pp. 168-175
animal models, antioxidant activity, blood sampling, blood serum, catalase, diamine oxidase, glutathione peroxidase, histology, inflammation, interleukin-6, intraperitoneal injection, lactic acid, lipopolysaccharides, males, malondialdehyde, mitogen-activated protein kinase, nitric oxide, occludins, oral administration, oxidative stress, phosphorylation, protective effect, rats, small intestine, tumor necrosis factor-alpha
In this study, we explored the underlying mechanisms of protective effects of rhein against intestinal barrier injury in a rat model, induced by intraperitoneal injection of lipopolysaccharide (LPS).Twenty-four male rats were assigned equally to three groups. Rats were given an oral administration of rhein (66.7 mg/kg/day) or not for three continuous days. LPS or saline were injected intraperitoneally in an hour after the last oral administration. The rats were sacrificed at 7 h after LPS or saline administration. Both blood samples and intestinal samples were collected.Rhein pretreatment markedly inhibited the levels of serum diamine oxidase (DAO), D-lactate (D-lac) and intestinal histological damage, significantly recovered the levels of intestinal DAO, ZO-1 and occludin. Additionally, rhein suppressed LPS-induced intestinal inflammation and oxidative stress, by decreased serum and intestinal, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and nitric oxide levels, up-regulated intestinal catalase, glutathione peroxidase (GSH-Px) activities and HO-1 expression, and down-regulated malondialdehyde (MDA) level in the small intestine. Finally, rhein inhibited JNK, p38 MAPK phosphorylation and activated Nrf2 pathway.Rhein could exert the anti-inflammatory and anti-oxidative effects against LPS-induced intestinal barrier injury by suppressing p38 MAPK and JNK and activating Nrf2 pathway.