PMID- 29880071 OWN - NLM STAT- MEDLINE DCOM- 20190904 LR - 20190904 IS - 1475-2662 (Electronic) IS - 0007-1145 (Linking) VI - 120 IP - 4 DP - 2018 Aug TI - Curcumin attenuates hepatic fibrosis and insulin resistance induced by bile duct ligation in rats. PG - 393-403 LID - 10.1017/S0007114518001095 [doi] AB - Recent studies have strongly indicated the hepatoprotective effect of curcumin; however, the precise mechanisms are not well understood. This study aimed to determine the protective effect of curcumin on hepatic damage and hepatic insulin resistance in biliary duct ligated (BDL) fibrotic rat model. To accomplish this, male Wistar rats were divided into four groups (eight for each): sham group, BDL group, sham+Cur group and BDL+Cur group. The last two groups received curcumin at a dose of 100 mg/kg daily for 4 weeks. The mRNA/protein expression levels of Ras-related C3 botulinum toxin substrate 1 (Rac1), Rac1-GTP, dinucleotide phosphate oxidase 1 (NOX1), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signalling 3 (SOCS3), insulin receptor substrate 1 (IRS1), extracellular signal-regulated kinase 1 (ERK1), specific protein 1 (Sp1) and hypoxia-inducible factor-1alpha (HIF-1alpha) were measured by real-time PCR and Western blotting, respectively. Fasting blood glucose, insulin and Leptin levels were determined and homoeostasis model assessment-estimated insulin resistance, as an index of insulin resistance, was calculated. Curcumin significantly attenuated liver injury and fibrosis, including amelioration of liver histological changes, reduction of hepatic enzymes, as well as decreased expression of liver fibrogenesis-associated variables, including Rac1, Rac1-GTP, NOX1, ERK1, HIF-1alpha and Sp1. Curcumin also attenuated leptin level and insulin resistance, which had increased in BDL rats (P<0.05). Furthermore, compared with the BDL group, we observed an increase in IRS1 and a decrease in SOCS3 and STAT3 expression in the curcumin-treated BDL group (P<0.05), indicating return of these parameters towards normalcy. In conclusion, Curcumin showed hepatoprotective activity against BDL-induced liver injury and hepatic insulin resistance by influencing the expression of some genes/proteins involved in these processes, and the results suggest that it can be used as a therapeutic option. FAU - Eshaghian, Azam AU - Eshaghian A AD - 1Department of Biochemistry,School of Medicine,Shahid Sadoughi University of Medical Sciences and Health Services,Yazd,8915173149,Iran. FAU - Khodarahmi, Ameneh AU - Khodarahmi A AD - 1Department of Biochemistry,School of Medicine,Shahid Sadoughi University of Medical Sciences and Health Services,Yazd,8915173149,Iran. FAU - Safari, Fatemeh AU - Safari F AD - 2Department of Physiology,School of Medicine,Shahid Sadoughi University of Medical Sciences and Health Services,Yazd,8915173149,Iran. FAU - Binesh, Fariba AU - Binesh F AD - 3Department of Pathology,Shahid Sadoughi University of Medical Sciences,Yazd,8915173149,Iran. FAU - Moradi, Ali AU - Moradi A AD - 1Department of Biochemistry,School of Medicine,Shahid Sadoughi University of Medical Sciences and Health Services,Yazd,8915173149,Iran. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180608 PL - England TA - Br J Nutr JT - The British journal of nutrition JID - 0372547 RN - 0 (Hif1a protein, rat) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (Irs1 protein, rat) RN - 0 (STAT3 Transcription Factor) RN - 0 (Stat3 protein, rat) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.6.3.- (NADPH Oxidase 1) RN - EC 1.6.3.- (NOX1 protein, rat) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 3.6.1.- (Rac1 protein, rat) RN - EC 3.6.5.2 (rac1 GTP-Binding Protein) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - Bile Ducts/surgery MH - Curcumin/*pharmacology MH - Gene Expression Profiling MH - Homeostasis MH - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism MH - Inflammation MH - Insulin Receptor Substrate Proteins/metabolism MH - *Insulin Resistance MH - Ligation MH - Liver Cirrhosis/*drug therapy/pathology MH - Male MH - Malondialdehyde/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - NADPH Oxidase 1/metabolism MH - Rats MH - Rats, Wistar MH - STAT3 Transcription Factor/metabolism MH - rac1 GTP-Binding Protein/metabolism OTO - NOTNLM OT - BDL biliary duct ligated OT - DPPH 2 OT - ECM extracellular matrix OT - ERK1 extracellular signal-regulated kinase 1 OT - FBG fasting blood glucose OT - HIF-1alpha hypoxia-inducible factor-1alpha OT - HOMA-IR homoeostasis model assessment-estimated insulin resistance OT - HSC hepatic stellate cells OT - IR insulin resistance OT - IRS1 insulin receptor substrate 1 OT - JAK Janus kinase OT - MDA malondialdehyde OT - NOX1 dinucleotide phosphate oxidase 1 OT - ROS reactive oxygen species OT - Rac1 Ras-related C3 botulinum toxin substrate 1 OT - SOCS3 suppressor of cytokine signalling 3 OT - STAT3 signal transducer and activator of transcription 3 OT - Sp1 specific protein 1 OT - TGF-beta1 transforming growth factor-beta1 OT - iNOS inducible nitric oxide synthase OT - 2-diphenyl-1-picrylhydrazyl OT - Curcumin OT - Insulin receptor substrate 1 OT - Insulin resistance OT - Liver fibrosis OT - Suppressor of cytokine signalling 3 EDAT- 2018/06/09 06:00 MHDA- 2019/09/05 06:00 CRDT- 2018/06/09 06:00 PHST- 2018/06/09 06:00 [pubmed] PHST- 2019/09/05 06:00 [medline] PHST- 2018/06/09 06:00 [entrez] AID - S0007114518001095 [pii] AID - 10.1017/S0007114518001095 [doi] PST - ppublish SO - Br J Nutr. 2018 Aug;120(4):393-403. doi: 10.1017/S0007114518001095. Epub 2018 Jun 8.