PMID- 28595079 OWN - NLM STAT- MEDLINE DCOM- 20180501 LR - 20180501 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 49 DP - 2017 Aug TI - Curcumin reduces the risk of chronic kidney damage in mice with nonalcoholic steatohepatitis by modulating endoplasmic reticulum stress and MAPK signaling. PG - 161-167 LID - S1567-5769(17)30208-4 [pii] LID - 10.1016/j.intimp.2017.05.035 [doi] AB - Developing confirmation recommends that in patients with dynamic type of NAFLD, particularly nonalcoholic steatohepatitis (NASH) may have the pathogenic parts in the advancement of kidney damage. In this study we have examined the impact of curcumin on NASH instigated chronic kidney damage (CKD) and the putative mechanisms. To prepare this NASH model, neonatal C57BL/6J male mice were exposed to low-dose streptozotocin (STZ) and were fed high-fat diet (HFD) at the age of 4weeks and continued up to 14weeks, curcumin was given at 100mg/kg dose by oral gavage daily after 10weeks of STZ injection and continued for 4weeks along with HFD feeding. NASH incited mice demonstrated nephrotoxicity as proved by declining renal capacity, which was evaluated by measuring blood urea nitrogen and creatinine in serum and histopathological variations from the norm. These progressions were switched by curcumin treatment, which brought about huge change in renal capacity. Furthermore, curcumin markedly decreased NAD(P)H oxidase subunits (p67phox, p47phox, p22phox), nitrotyrosine and CYP2E1 renal protein expression as well as reduced pro-inflammatory cytokine expression (TNFalpha, IL-1beta, IFNgamma). Renal protein expression of mitogen activated protein kinases (MAPKs) (p-JNK, p-ERK1/2) and glucose regulated protein 78, CHOP were increased in NASH induced mice and curcumin treatment attenuated these increased expressions. In addition, curcumin treatment also decreased the apoptosis signaling proteins (cleaved caspase-3, cleaved caspase-12) in the NASH kidney. Taken together, our results suggest that curcumin preserves the renal function, probably by attenuating the ER stress mediated MAPK signaling. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Afrin, Mst Rejina AU - Afrin MR AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan. FAU - Arumugam, Somasundaram AU - Arumugam S AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan; Department of Hematology, Endocrinology and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, Niigata City 951-8510, Japan. Electronic address: somasundaram@med.niigata-u.ac.jp. FAU - Rahman, Md Azizur AU - Rahman MA AD - Department of Immunology and Medical Zoology, Faculty of Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata City 951-8510, Japan. FAU - Karuppagounder, Vengadeshprabhu AU - Karuppagounder V AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan. FAU - Harima, Meilei AU - Harima M AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan. FAU - Suzuki, Hiroshi AU - Suzuki H AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan; Department of Hematology, Endocrinology and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, Niigata City 951-8510, Japan. FAU - Miyashita, Shizuka AU - Miyashita S AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan. FAU - Suzuki, Kenji AU - Suzuki K AD - Department of Clinical Engineering and Medical Technology, Niigata University of Health and Welfare, Niigata City 950-3198, Japan. FAU - Ueno, Kazuyuki AU - Ueno K AD - Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan. FAU - Yoneyama, Hiroyuki AU - Yoneyama H AD - Stelic Institute & Co., Inc., Minato City, Tokyo 106-0044, Japan. FAU - Watanabe, Kenichi AU - Watanabe K AD - Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan; Department of Hematology, Endocrinology and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, Niigata City 951-8510, Japan. Electronic address: kenichiwatanabe2000@gmail.com. LA - eng PT - Journal Article DEP - 20170605 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 5W494URQ81 (Streptozocin) RN - AYI8EX34EU (Creatinine) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use MH - Apoptosis MH - Blood Urea Nitrogen MH - Creatinine/blood MH - Curcumin/*therapeutic use MH - Diet, High-Fat MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Humans MH - Kidney/*metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NADPH Oxidases/metabolism MH - Non-alcoholic Fatty Liver Disease/*drug therapy MH - Renal Insufficiency, Chronic/*drug therapy MH - Signal Transduction MH - Streptozocin/administration & dosage OTO - NOTNLM OT - Chronic kidney damage OT - ER stress OT - MAPK OT - Non-alcoholic fatty liver disease OT - Oxidative stress EDAT- 2017/06/09 06:00 MHDA- 2018/05/02 06:00 CRDT- 2017/06/09 06:00 PHST- 2016/12/23 00:00 [received] PHST- 2017/05/16 00:00 [revised] PHST- 2017/05/29 00:00 [accepted] PHST- 2017/06/09 06:00 [pubmed] PHST- 2018/05/02 06:00 [medline] PHST- 2017/06/09 06:00 [entrez] AID - S1567-5769(17)30208-4 [pii] AID - 10.1016/j.intimp.2017.05.035 [doi] PST - ppublish SO - Int Immunopharmacol. 2017 Aug;49:161-167. doi: 10.1016/j.intimp.2017.05.035. Epub 2017 Jun 5.