Effects of Camel Whey Protein on Hepatic Inflammation and High Mobility Group Protein B1/Toll Like Receptor 4/Nuclear Factor-&kappa;B Signaling Pathway in Heat Stressed Rats

WUENJiya; DU Donghua; MA Xueni; HASISurong

doi:10.3969/j.issn.1006-267x.2021.10.040

2021 , Vol. 33 >Issue 10: 5809 - 5816

DOI: https://doi.org/10.3969/j.issn.1006-267x.2021.10.040

MOLECULAR AND CELLULAR NUTRITION

Effects of Camel Whey Protein on Hepatic Inflammation and High Mobility Group Protein B1/Toll Like Receptor 4/Nuclear Factor-κB Signaling Pathway in Heat Stressed Rats

WUENJiya ,
DU Donghua ,
MA Xueni ,
HASISurong

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1. 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;
2. College of Animal Science and Technology, Hebei North University, Zhangjiakou 075131, China;
3. Inner Mongolia institute of Camel Research, Alashan 750300, China

Received date: 2021-03-24

Online published: 2021-10-16

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Abstract

This experiment was aimed to investigate the regulatory effects of camel whey protein (CWP) on hepatic inflammatory and relative signaling pathways in rats induced by heat stress (HS). SD rats at 6 weeks of age were selected and randomly divided into six groups after 2 weeks of adaptive feeding, with five replicates in each group, six in each replicate, and test period was 22 d. The normal control group (Control group) was fed a basal diet. The CWP control group (CWP group) fed 400 mg/kg BW CWP daily. HS induced liver injury group (HS group) was fed the basal diet and subjected to 2 h HS treatment daily from day 15 for 8 d. CWP low-, medium-, and high-dose intervention groups (L, M and H groups) were received 100, 200, and 400 mg/kg BW CWP daily and subjected to 2 h HS treatment daily for 8 consecutive days starting at day 15. Hepatic tumor necrosis factor-α (TNF-α), interleukins-1β (IL-1β), interleukins-6 (IL-6), interleukins-8 (IL-8), and interleukins-10 (IL-10) contents were measured by enzyme linked immunosorbent assay (ELISA), and hepatic high mobility group protein B1 (HMGB1), Toll like receptor 4 (TLR4), and phosphorylated nuclear factor-κB (p-NF-κB p65) protein expression was detected by immunohistochemistry and Western blotting. The results showed as follows:1) compared with the HS group, CWP intervention at 400 mg/kg effectively reduced hepatic TNF-α, IL-1β, IL-6 and IL-8 contents (P<0.05) and increased IL-10 content in HS rats (P<0.05). 2) Compared with the HS group, CWP reduced the nuclear translocation of HMGB1 protein in the liver of HS rats in a dose-dependent manner (P<0.01), but had no effect on the total protein expression (P>0.05), while it extremely significantly reduced TLR4 protein expression (P<0.001), significantly reduced p-NF-κB p65 protein expression (P<0.01) and nuclear translocation. Compared with the Control group, CWP intervention at 400 mg/kg had the best effect. Thus, it is concluded that CWP at 400 mg/kg administered before HS modulates the hepatic HMGB1/TLR4/NF-κB signaling pathway and alleviates inflammatory responses in HS rats.

Key words： camel whey protein; rat; liver; inflammatory response; signaling pathway; heat stress

Cite this article

WUENJiya , DU Donghua , MA Xueni , HASISurong . Effects of Camel Whey Protein on Hepatic Inflammation and High Mobility Group Protein B1/Toll Like Receptor 4/Nuclear Factor-κB Signaling Pathway in Heat Stressed Rats[J]. Chinese Journal of Animal Nutrition, 2021 , 33(10) : 5809 -5816 . DOI: 10.3969/j.issn.1006-267x.2021.10.040

References

[1] AKBARIAN A, MICHIELS J, DEGROOTE J, et al.Association between heat stress and oxidative stress in poultry;mitochondrial dysfunction and dietary interventions with phytochemicals[J].Journal of Animal Science and Biotechnology, 2016, 7:37.
[2] RAMADAN N K, BADR G, ABDEL-TAWAB H S, et al.Camel whey protein enhances lymphocyte survival by modulating the expression of survivin, bim/bax, and cytochrome C and restores heat stress-mediated pathological alteration in lymphoid organs[J].Iranian Journal of Basic Medical Sciences, 2018, 21(9):896-904.
[3] SLIMEN I B, NAJAR T, GHRAM A, et al.Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage.A review[J].International Journal of Hyperthermia, 2014, 30(7):513-523.

[4] GENG Y, MA Q, LIU Y N, et al.Heatstroke induces liver injury via IL-1β and HMGB1-induced pyroptosis[J].Journal of Hepatology, 2015, 63(3):622-633.

[5] YU R Q, JIANG S Y, TAO Y Q, et al.Inhibition of HMGB1 improves necrotizing enterocolitis by inhibiting NLRP3 via TLR4 and NF-κB signaling pathways[J].Journal of Cellular Physiology, 2019, 234(8):13431-13438.

[6] AVGOUSTI D C, HERRMANN C, KULEJ K, et al.A core viral protein binds host nucleosomes to sequester immune danger signals[J].Nature, 2016, 535(7610):173-177.

[7] TAKIZAWA T, SHIBATA M, KAYAMA Y, et al.High-mobility group box 1 is an important mediator of microglial activation induced by cortical spreading depression[J].Journal of Cerebral Blood Flow and Metabolism:Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 2017, 37(3):890-901.

[8] LI Z Y, CHEN D D, JIA Y F, et al.Methane-rich saline counteracts cholestasis-induced liver damage via regulating the TLR4/NF-κB/NLRP3 inflammasome pathway[J].Oxidative Medicine and Cellular Longevity, 2019, 2019:6565283.
[9] ANDERSSON U, TRACEY K J.HMGB1 is a therapeutic target for sterile inflammation and infection[J].Annual Review of Immunology, 2011, 29:139-162.
[10] BADR G, ABDEL-TAWAB H S, RAMADAN N K, et al.Protective effects of camel whey protein against scrotal heat-mediated damage and infertility in the mouse testis through YAP/Nrf2 and PPAR-gamma signaling pathways[J].Molecular Reproduction and Development, 2018, 85(6):505-518.
[11] BADR G.Camel whey protein enhances diabetic wound healing in a streptozotocin-induced diabetic mouse model:the critical role of β-defensin-1, -2 and -3[J].Lipids in Health and Disease, 2013, 12:46.
[12] MIHIC T, RAINKIE D, WILBY K J, et al.The therapeutic effects of camel milk:a systematic review of animal and human trials[J].Journal of Evidence-based Complementary & Alternative Medicine, 2016, 21(4):NP110-NP126.
[13] DU D H, LV W T, SU R, et al.Hydrolyzed camel whey protein alleviated heat stress-induced hepatocyte damage by activated Nrf2/HO-1 signaling pathway and inhibited NF-κB/NLRP3 axis[J].Cell Stress & Chaperones, 2021, 26(2):387-401.

[14] LIAN C J, WANG X D, QIU X J, et al.Collagen type Ⅱ suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin β1-SMAD1 interaction[J].Bone Research, 2019, 7:8.
[15] BADR G, RAMADAN N K, ABDEL-TAWAB H S, et al.Camel whey protein protects lymphocytes from apoptosis via the PI3K-AKT, NF-κB, ATF-3, and HSP-70 signaling pathways in heat-stressed male mice[J].Biochemistry and Cell Biology, 2018, 96(4):407-416.

[16] HASSANEIN T, RAZACK A, GAVALER J S, et al.Heatstroke:its clinical and pathological presentation, with particular attention to the liver[J].The American Journal of Gastroenterology, 1992, 87(10):1382-1389.
[17] KEW M, BERSOHN I, SEFTEL H, et al.Liver damage in heatstroke[J].The American Journal of Medicine, 1970, 49(2):192-202.

[18] WEIGAND K, RIEDIGER C, STREMMEL W, et al.Are heat stroke and physical exhaustion underestimated causes of acute hepatic failure?[J].World Journal of Gastroenterology, 2007, 13(2):306-309.

[19] LEON L R.Heat stroke and cytokines[J].Progress in Brain Research, 2007, 162:481-524.
[20] BADR G, RAMADAN N K, SAYED L H, et al.Why whey?camel whey protein as a new dietary approach to the management of free radicals and for the treatment of different health disorders[J].Iranian Journal of Basic Medical Sciences, 2017, 20(4):338-349.
[21] KAMAL H, JAFAR S, MUDGIL P, et al.Inhibitory properties of camel whey protein hydrolysates toward liver cancer cells, dipeptidyl peptidase-Ⅳ, and inflammation[J].Journal of Dairy Science, 2018, 101(10):8711-8720.

[22] PARK J S, GAMBONI-ROBERTSON F, HE Q B, et al.High mobility group box 1 protein interacts with multiple Toll-like receptors[J].American Journal of Physiology-Cell Physiology, 2006, 290(3):C917-C924.
[23] YIN H F, HUANG L H, OUYANG T, et al.Baicalein improves liver inflammation in diabetic db/db mice by regulating HMGB1/TLR4/NF-κB signaling pathway[J].International Immunopharmacology, 2018, 55:55-62.

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