PMID- 30194055 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 227 DP - 2018 Dec 5 TI - Sagittaria sagittifolia polysaccharide protects against isoniazid- and rifampicin-induced hepatic injury via activation of nuclear factor E2-related factor 2 signaling in mice. PG - 237-245 LID - S0378-8741(18)30221-6 [pii] LID - 10.1016/j.jep.2018.09.002 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: The Sagittaria sagittifolia L. polysaccharide (SSP) is a purified form of a homogeneous polysaccharide isolated from the root tubers of S. sagittifolia, which has been used as a protectant against hepatotoxicity induced by coadministration of isoniazid and rifampicin. However, the protective effect of SSP against isoniazid- and rifampicin-induced liver injury has never been studied. AIM OF THE STUDY: In this study, the hepatoprotective effect of SSP and its underlying mechanism were investigated in mice with isoniazid- and rifampicin-induced liver injury. MATERIALS AND METHODS: Liver injury was induced in mice by intragastric administration of isoniazid and rifampicin, and the mice were divided into the following six groups: standard control (administration of saline by gavage), model (intragastric administration of isoniazid and rifampicin at 100 mg/kg/day each), positive control (100 mg/kg/day silymarin by gavage 4 h after isoniazid and rifampicin administration), and SSP-treated (200, 400, or 800 mg/kg/day SSP by gavage after isoniazid and rifampicin administration). Subsequently, blood and liver samples were collected from all the animals and were assessed. RESULTS: SSP significantly alleviated the liver injury, as evidenced by decreased activities of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase in the serum and a decreased level of malondialdehyde in the liver, as well as by an increased level of glutathione and increased activities of superoxide dismutase and catalase in the liver. SSP also effectively reduced the pathological tissue damage. The gene and protein expression of cytochrome P450 (CYP) 2E1 and CYP3A4 was inhibited by SSP. The gene and protein expression of nuclear factor erythroid 2-related factor 2 (NRF2), glutamate-cysteine ligase, and heme oxygenase-1 were induced by SSP, whereas that of Kelch-like ECH-associated protein 1 was inhibited. CONCLUSIONS: SSP exerts a protective effect against isoniazid- and rifampicin-induced liver injury in mice. The underlying mechanisms may involve activation of NRF2 and its target antioxidant enzymes and inhibition of the expression of CYPs. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Wang, Jing AU - Wang J AD - Chinese Medical Institute, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. FAU - Luo, Weizao AU - Luo W AD - Chongqing Academy of Chinese Materia Medical, 34 Huangjuezhen Pass South Road, Nan'an Qu, Chongqing 400065, China. FAU - Li, Bing AU - Li B AD - Chinese Medical Institute, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. FAU - Lv, Junping AU - Lv J AD - Beijing Institute of Biomedicine, 15 New Palace Gate Road, Haidian Qu, Beijing 100091, China. FAU - Ke, Xiuhui AU - Ke X AD - Chinese Medical Institute, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. FAU - Ge, Dongyu AU - Ge D AD - Chinese Medical Institute, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. FAU - Dong, Ruijuan AU - Dong R AD - Chinese Medical Institute, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. FAU - Wang, Chunguo AU - Wang C AD - School of Chinese Materia Medical, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. FAU - Han, Yue AU - Han Y AD - Chinese Medical Institute, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. FAU - Zhang, Cong AU - Zhang C AD - Chinese Medical Institute, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. FAU - Yu, Haichuan AU - Yu H AD - Department of Orthopaedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, 5 Seaborne, Dongcheng Qu, Beijing 100700, China. FAU - Liao, Yan AU - Liao Y AD - Chinese Medical Institute, Beijing University of Chinese Medicine, 11N 3rd Ring Rd E, Chaoyang Qu, Beijing 100029, China. Electronic address: liaoyanaa@sohu.com. LA - eng PT - Journal Article DEP - 20180905 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Polysaccharides) RN - 0 (Protective Agents) RN - EC 1.14.13.- (Cytochrome P-450 CYP2E1) RN - EC 1.14.14.1 (Cytochrome P-450 CYP3A) RN - EC 1.14.14.1 (cytochrome P450 3A4, mouse) RN - V83O1VOZ8L (Isoniazid) RN - VJT6J7R4TR (Rifampin) SB - IM MH - Animals MH - Chemical and Drug Induced Liver Injury/drug therapy/*metabolism/pathology MH - Cytochrome P-450 CYP2E1/genetics MH - Cytochrome P-450 CYP3A/genetics MH - Isoniazid MH - Male MH - Mice, Inbred BALB C MH - NF-E2-Related Factor 2/*metabolism MH - Polysaccharides/*pharmacology/therapeutic use MH - Protective Agents/*pharmacology/therapeutic use MH - Rifampin MH - *Sagittaria MH - Signal Transduction/drug effects OTO - NOTNLM OT - CYP2E1 OT - CYP3A4 OT - Hepatoprotective mechanism OT - NRF2 signaling EDAT- 2018/09/09 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/09/09 06:00 PHST- 2018/01/20 00:00 [received] PHST- 2018/08/22 00:00 [revised] PHST- 2018/09/02 00:00 [accepted] PHST- 2018/09/09 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/09/09 06:00 [entrez] AID - S0378-8741(18)30221-6 [pii] AID - 10.1016/j.jep.2018.09.002 [doi] PST - ppublish SO - J Ethnopharmacol. 2018 Dec 5;227:237-245. doi: 10.1016/j.jep.2018.09.002. Epub 2018 Sep 5.