PMID- 33405053 OWN - NLM STAT- MEDLINE DCOM- 20211215 LR - 20240229 IS - 1466-1268 (Electronic) IS - 1355-8145 (Print) IS - 1355-8145 (Linking) VI - 26 IP - 2 DP - 2021 Mar TI - Hydrolyzed camel whey protein alleviated heat stress-induced hepatocyte damage by activated Nrf2/HO-1 signaling pathway and inhibited NF-kappaB/NLRP3 axis. PG - 387-401 LID - 10.1007/s12192-020-01184-z [doi] AB - Liver damage is the most severe complication of heat stress (HS). Hydrolyzed camel whey protein (CWP) possesses bioactive peptides with obviously antioxidant and anti-inflammatory activities. The current study aims to investigate whether CWP that is hydrolyzed by a simulated gastrointestinal digestion process, named S-CWP, protects BRL-3A hepatocytes from HS-induced damage via antioxidant and anti-inflammatory mechanisms. BRL-3A cells were pretreated with S-CWP before being treated at 43 degrees C for 1 h, and the levels of the cellular oxidative stress, inflammation, apoptosis, biomarkers for liver function, the activities of several antioxidant enzymes, and the cell viability were analyzed. The expression level of pivotal proteins in correlative signaling pathways was evaluated by western blotting. We confirmed that S-CWP alleviated HS-induced hepatocytes oxidative stress by decreased reactive oxygen species (ROS), nitric oxide (NO), 8-Hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation (LPO), protein carbonylation (PCO), and the activities of NADPH oxidase while enhanced superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), heme oxygenase-1 (HO-1) activities, and GSH content. S-CWP suppressed HS-induced inflammatory response by reducing the phosphorylation of NF-kappaB p65, the expression of NLRP3, and caspase-1 and finally alleviated caspase-3-mediated apoptosis. S-CWP also alleviated HS-induced hepatocyte injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and restoring Heat Shock Protein 70 (HSP70) expression. Furthermore, S-CWP treatment significantly enhanced the expression of NF-E2-related nuclear factor erythroid-2 (Nrf2) and HO-1. The antioxidant and anti-inflammatory effects of S-CWP were weakened by ML385, a specific Nrf2 inhibitor. Additionally, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, significantly reversed S-CWP-induced reduction in the phosphorylation of NF-kappaB p65. Thus, our results revealed that S-CWP protected against HS-induced hepatocytes damage via activating the Nrf2/HO-1 signaling pathway and inhibiting NF-kappaB/NLRP3 axis. FAU - Du, Donghua AU - Du D AD - Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. AD - Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, 075131, Hebei, China. FAU - Lv, Wenting AU - Lv W AD - Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. AD - Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou, 075131, Hebei, China. FAU - Su, Rina AU - Su R AD - Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. FAU - Yu, Chunwei AU - Yu C AD - Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. FAU - Jing, Xiaoxia AU - Jing X AD - Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. FAU - Bai, Nuwenqimuge AU - Bai N AD - Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. FAU - Hasi, Surong AU - Hasi S AD - Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, 010018, China. surong@imau.edu.cn. AD - Inner Mongolia institute of Camel Research, Badain Jaran, 075131, Inner Mongolia, China. surong@imau.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210106 PL - Netherlands TA - Cell Stress Chaperones JT - Cell stress & chaperones JID - 9610925 RN - 0 (Antioxidants) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Hmox1 protein, rat) RN - 0 (Milk Proteins) RN - 0 (NF-E2-Related Factor 2) SB - IM MH - Animals MH - Rats MH - Antioxidants/pharmacology MH - Apoptosis/drug effects MH - *Camelus MH - Cell Line MH - Heme Oxygenase (Decyclizing)/metabolism MH - *Hepatocytes/drug effects MH - *Milk Proteins/pharmacology MH - *Oxidative Stress/drug effects MH - NF-E2-Related Factor 2 PMC - PMC7925754 OTO - NOTNLM OT - Apoptosis OT - Camel whey protein OT - Heat stress OT - Hepatocyte OT - Oxidative stress COIS- The authors declare that they have no conflict of interest. EDAT- 2021/01/07 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/09/01 CRDT- 2021/01/06 12:21 PHST- 2020/07/15 00:00 [received] PHST- 2020/11/27 00:00 [accepted] PHST- 2020/11/16 00:00 [revised] PHST- 2021/01/07 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/01/06 12:21 [entrez] PHST- 2021/09/01 00:00 [pmc-release] AID - S1355-8145(23)00527-8 [pii] AID - 1184 [pii] AID - 10.1007/s12192-020-01184-z [doi] PST - ppublish SO - Cell Stress Chaperones. 2021 Mar;26(2):387-401. doi: 10.1007/s12192-020-01184-z. Epub 2021 Jan 6.