Dietary supplementation of camel whey protein attenuates heat stress-induced liver injury by inhibiting NLRP3 inflammasome activation through the HMGB1/RAGE signalling pathway
Inflammasomes play an important role in promoting heat stress (HS) induced liver injury. Dietary supplementation of camel whey protein (CWP) has been shown to alleviate HS-induced tissue damage. However, whether and how dietary CWP supplementation can reduce HS-induced liver injury remains unclear....
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Elsevier
2021-09-01
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Series: | Journal of Functional Foods |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464621002334 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Donghua Du Wenting Lv Xiaoxia Jing Xueni Ma Jiya Wuen Surong Hasi |
spellingShingle |
Donghua Du Wenting Lv Xiaoxia Jing Xueni Ma Jiya Wuen Surong Hasi Dietary supplementation of camel whey protein attenuates heat stress-induced liver injury by inhibiting NLRP3 inflammasome activation through the HMGB1/RAGE signalling pathway Journal of Functional Foods Heat stress Liver injury Camel whey protein NLRP3 HMGB1 |
author_facet |
Donghua Du Wenting Lv Xiaoxia Jing Xueni Ma Jiya Wuen Surong Hasi |
author_sort |
Donghua Du |
title |
Dietary supplementation of camel whey protein attenuates heat stress-induced liver injury by inhibiting NLRP3 inflammasome activation through the HMGB1/RAGE signalling pathway |
title_short |
Dietary supplementation of camel whey protein attenuates heat stress-induced liver injury by inhibiting NLRP3 inflammasome activation through the HMGB1/RAGE signalling pathway |
title_full |
Dietary supplementation of camel whey protein attenuates heat stress-induced liver injury by inhibiting NLRP3 inflammasome activation through the HMGB1/RAGE signalling pathway |
title_fullStr |
Dietary supplementation of camel whey protein attenuates heat stress-induced liver injury by inhibiting NLRP3 inflammasome activation through the HMGB1/RAGE signalling pathway |
title_full_unstemmed |
Dietary supplementation of camel whey protein attenuates heat stress-induced liver injury by inhibiting NLRP3 inflammasome activation through the HMGB1/RAGE signalling pathway |
title_sort |
dietary supplementation of camel whey protein attenuates heat stress-induced liver injury by inhibiting nlrp3 inflammasome activation through the hmgb1/rage signalling pathway |
publisher |
Elsevier |
series |
Journal of Functional Foods |
issn |
1756-4646 |
publishDate |
2021-09-01 |
description |
Inflammasomes play an important role in promoting heat stress (HS) induced liver injury. Dietary supplementation of camel whey protein (CWP) has been shown to alleviate HS-induced tissue damage. However, whether and how dietary CWP supplementation can reduce HS-induced liver injury remains unclear. Thus, we evaluated the ability of rats supplemented with CWP to resist HS-induced liver injury. To induce liver injury, Sprague-Dawley rats were exposed to HS. The mechanism of action was confirmed using an antagonist of high mobility group box 1 (HMGB1) and the NLR pyrin domain containing 3 (NLRP3) inhibitor before HS. Histological changes in the livers of the HS rats were visualised using haematoxylin and eosin staining. The protein expression of HMG1, receptor for advanced glycation end products (RAGE), NLRP3, Caspase-3, and Bcl-2 were detected using immunohistochemistry or western blotting. The content of IL-1β, the activation of Caspase-1, and the level of alanine transaminase (ALT) were determined using commercial kits. We confirmed that HS activated NLRP3 in the liver, as evidenced by enhanced Caspase-1 activity and increased IL-1β content. Inhibition of NLRP3 activation reversed abnormal expression and nuclear translocation of Caspase-3 and Bcl-2, and alleviated apoptosis, necrosis, and subsequent liver injury. HS-induced hepatocyte NLRP3 activation is dependent on elevated extracellular HMGB1 levels. Glycyrrhizic acid, an antagonist of HMGB1, which is also an anti-inflammatory agent, inhibited HS-induced NLRP3 activation. Interestingly, CWP also reversed HS-induced abnormal expression of HMGB1, RAGE, NLRP3, IL-1β, ALT, Bcl-2, and Caspase-3, inhibited Caspase-1 activity, and alleviated apoptosis and liver histological changes. More importantly, CWP combined with glycyrrhizic acid completely prevented HS-induced hepatocyte apoptosis and injury. These results indicate that CWP ameliorates HS-induced liver injury by inhibiting the HMGB1/RAGE/NLRP3 axis. Dietary supplementation with CWP may be an effective strategy to prevent serious complications from HS. |
topic |
Heat stress Liver injury Camel whey protein NLRP3 HMGB1 |
url |
http://www.sciencedirect.com/science/article/pii/S1756464621002334 |
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doaj-59f767fd88ca4d67b7b7befde9fbb1022021-07-13T04:09:01ZengElsevierJournal of Functional Foods1756-46462021-09-0184104584Dietary supplementation of camel whey protein attenuates heat stress-induced liver injury by inhibiting NLRP3 inflammasome activation through the HMGB1/RAGE signalling pathwayDonghua Du0Wenting Lv1Xiaoxia Jing2Xueni Ma3Jiya Wuen4Surong Hasi5Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease/Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China; Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou 075131, Hebei, ChinaKey Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease/Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China; Department of Veterinary Medicine, College of Animal Science and Technology, Hebei North University, Zhangjiakou 075131, Hebei, ChinaKey Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease/Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, ChinaKey Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease/Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, ChinaKey Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease/Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, ChinaKey Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease/Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China; Inner Mongolia Institute of Camel Research, Alashan 750300, Inner Mongolia, China; Corresponding author at: Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease/Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot 010018, China.Inflammasomes play an important role in promoting heat stress (HS) induced liver injury. Dietary supplementation of camel whey protein (CWP) has been shown to alleviate HS-induced tissue damage. However, whether and how dietary CWP supplementation can reduce HS-induced liver injury remains unclear. Thus, we evaluated the ability of rats supplemented with CWP to resist HS-induced liver injury. To induce liver injury, Sprague-Dawley rats were exposed to HS. The mechanism of action was confirmed using an antagonist of high mobility group box 1 (HMGB1) and the NLR pyrin domain containing 3 (NLRP3) inhibitor before HS. Histological changes in the livers of the HS rats were visualised using haematoxylin and eosin staining. The protein expression of HMG1, receptor for advanced glycation end products (RAGE), NLRP3, Caspase-3, and Bcl-2 were detected using immunohistochemistry or western blotting. The content of IL-1β, the activation of Caspase-1, and the level of alanine transaminase (ALT) were determined using commercial kits. We confirmed that HS activated NLRP3 in the liver, as evidenced by enhanced Caspase-1 activity and increased IL-1β content. Inhibition of NLRP3 activation reversed abnormal expression and nuclear translocation of Caspase-3 and Bcl-2, and alleviated apoptosis, necrosis, and subsequent liver injury. HS-induced hepatocyte NLRP3 activation is dependent on elevated extracellular HMGB1 levels. Glycyrrhizic acid, an antagonist of HMGB1, which is also an anti-inflammatory agent, inhibited HS-induced NLRP3 activation. Interestingly, CWP also reversed HS-induced abnormal expression of HMGB1, RAGE, NLRP3, IL-1β, ALT, Bcl-2, and Caspase-3, inhibited Caspase-1 activity, and alleviated apoptosis and liver histological changes. More importantly, CWP combined with glycyrrhizic acid completely prevented HS-induced hepatocyte apoptosis and injury. These results indicate that CWP ameliorates HS-induced liver injury by inhibiting the HMGB1/RAGE/NLRP3 axis. Dietary supplementation with CWP may be an effective strategy to prevent serious complications from HS.http://www.sciencedirect.com/science/article/pii/S1756464621002334Heat stressLiver injuryCamel whey proteinNLRP3HMGB1 |