Pre-treatment with galectin-1 attenuates lipopolysaccharide-induced myocarditis by regulating the Nrf2 pathway

Galectin-1 (Gal-1), a member of a highly conserved family of animal lectins, plays a crucial role in controlling inflammation and neovascularization. However, the potential role of Gal-1 in preventing myocarditis remains uncertain. We aimed to explore the functions and mechanisms of Gal-1 in preventing myocarditis. In vivo, C57/BL6 mice were pre-treated with or without Gal-1 and then exposed to lipopolysaccharide (LPS) to induce myocarditis. Subsequently, cardiac function, histopathology, inflammation, oxidative stress, and apoptosis of myocardial tissues were detected. Following this, qRT-PCR and Western blotting were applied to measure iNOS, COX2, TXNIP, NLRP3 and Caspase-1 p10 expressions. In vitro, H9c2 cells pre-treated with different doses of Gal-1 were stimulated by LPS to induce myocarditis models. CCK8, flow cytometry and reactive oxygen species (ROS) assay were then employed to estimate cell viability, apoptosis and oxidative stress. Furthermore, Nrf2 and HO-1 protein expressions were evaluated by Western blotting in vivo and in vitro. The results showed that in vivo, Gal-1 pre-treatment not only moderately improved cardiac function and cardiomyocyte apoptosis, but also ameliorated myocardial inflammation and oxidative damage in mice with myocarditis. Furthermore, Gal-1 inhibited TXNIP-NLRP3 inflammasome activation. In vitro, Gal-1 pre-treatment prevented LPS-induced apoptosis, cell viability decrease and ROS generation. Notably, Gal-1 elevated HO-1, total Nrf2 and nuclear Nrf2 protein expressions both in vivo and in vitro. In conclusion, pre-treatment with Gal-1 exhibited cardioprotective effects in myocarditis via anti-inflammatory and antioxidant functions, and the mechanism may relate to the Nrf2 pathway, which offered new solid evidence for the use of Gal-1 in preventing myocarditis.

Dimensions

Altmetric

PlumX Metrics

Downloads

Publication Facts

This article

Author statements

Data availability

N/A

16%

External funding

N/A

32%

Competing interests

N/A

11%

This journal

Other journals

Articles accepted

58%

33%

Days to publication

161

145

Indexed in

GS
M
S
WS

Editor & editorial board: profiles
Academic society: N/A
Publisher: PAGEPress Publications, Pavia, Italy

PFL

How useful do you find this label?

	1	2	3	4	5
Not useful						Very useful

I'm associated with...

Citations

Chen L, Hou X, Zhang M, Zheng Y, Zheng X, Yang Q, et al. MicroRNA-223-3p modulates dendritic cell function and ameliorates experimental autoimmune myocarditis by targeting the NLRP3 inflammasome. Mol Immunol 2020;117:73-83. DOI: https://doi.org/10.1016/j.molimm.2019.10.027

Fan S, Hu K, Zhang D, Liu F. Interference of circRNA HIPK3 alleviates cardiac dysfunction in lipopolysaccharide-induced mice models and apoptosis in H9C2 cardiomyocytes. Ann Transl Med 2020;8:1147. DOI: https://doi.org/10.21037/atm-20-5306

Hou X, Fu M, Cheng B, Kang Y, Xie D. Galanthamine improves myocardial ischemia-reperfusion-induced cardiac dysfunction, endoplasmic reticulum stress-related apoptosis, and myocardial fibrosis by suppressing AMPK/Nrf2 pathway in rats. Ann Transl Med 2019;7:634. DOI: https://doi.org/10.21037/atm.2019.10.108

Padappayil R, Chandini Arjun A, Vivar Acosta J, Ghali W, Mughal M. Acute myocarditis from the use of selective androgen receptor modulator (SARM) RAD-140 (testolone). Cureus 2022;14:e21663. DOI: https://doi.org/10.7759/cureus.21663

Al-Obaidi N, Mohan S, Liang S, Zhao Z, Nayak B, Li B, et al. Galectin-1 is a new fibrosis protein in type 1 and type 2 diabetes. FASEB J 2019;33:373-87. DOI: https://doi.org/10.1096/fj.201800555RR

Naqvi M, Memon M, Jamil T, Naqvi S, Aimulajiang K, Gadahi J, et al. Galectin domain containing protein from Haemonchus contortus modulates the immune functions of goat PBMCS and regulates CD4+ T-helper cells in vitro. Biomolecules 2020;10:116. DOI: https://doi.org/10.3390/biom10010116

Brinchmann M, Patel D, Iversen M. The role of galectins as modulators of metabolism and inflammation. Mediators Inflamm 2018;2018:9186940. DOI: https://doi.org/10.1155/2018/9186940

Hisrich B, Young R, Sansone A, Bowens Z, Green L, Lessey B, et al. Role of human galectins in inflammation and cancers associated with endometriosis. Biomolecules 2020;10:230. DOI: https://doi.org/10.3390/biom10020230

van der Hoeven N, Hollander M, Yıldırım C, Jansen M, Teunissen P, Horrevoets A, et al. The emerging role of galectins in cardiovascular disease. Vascul Pharmacol 2016;81:31-41. DOI: https://doi.org/10.1016/j.vph.2016.02.006

Seropian I, Cerliani J, Toldo S, Van Tassell B, Ilarregui J, González G, et al. Galectin-1 controls cardiac inflammation and ventricular remodeling during acute myocardial infarction. Am J Pathol 2013;182:29-40. DOI: https://doi.org/10.1016/j.ajpath.2012.09.022

Wang R, Li D, Ouyang J, Tian X, Zhao Y, Peng X, et al. Leonurine alleviates LPS-induced myocarditis through suppressing the NF-кB signaling pathway. Toxicology 2019;422:1-13. DOI: https://doi.org/10.1016/j.tox.2019.04.011

Liu Y, Lou G, Li A, Zhang T, Qi J, Ye D, et al. AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages. EBioMedicine 2018;36:140-50. DOI: https://doi.org/10.1016/j.ebiom.2018.08.054

Steinl D, Xu L, Ochoa-Espinosa A, Punjabi M, Kaufmann B. Non-invasive contrast enhanced ultrasound molecular imaging of inflammation in autoimmune myocarditis for prediction of left ventricular fibrosis and remodeling. PLoS One 2019;14:e0224377. DOI: https://doi.org/10.1371/journal.pone.0224377

Jiang X, Tang Q, Zhang J, Wang H, Bai L, Meng P, et al. Autophagy-dependent release of zinc ions is critical for acute lung injury triggered by zinc oxide nanoparticles. Nanotoxicology 2018;12:1068-91. DOI: https://doi.org/10.1080/17435390.2018.1513094

Paknahad M, Yancheshmeh F, Soleimani A. Cardiovascular complications of COVID-19 vaccines: A review of case-report and case-series studies. Heart Lung 2023;59:173-80. DOI: https://doi.org/10.1016/j.hrtlng.2023.02.003

Dobrică E, Cozma M, Găman M, Voiculescu V, Găman A. The involvement of oxidative stress in psoriasis: a systematic review. Antioxidants (Basel) 2022;11:282. DOI: https://doi.org/10.3390/antiox11020282

Hu Y, Wang J, Du W, Wu N, Wang S, Zhang C, et al. Antiresistin neutralizing antibody alleviates doxorubicin-induced cardiac injury in mice. Dis Markers 2022;2022:3040521. DOI: https://doi.org/10.1155/2022/3040521

Chou M, Lee Y, Wang Y, Cheng S, Cheng H. Cytotoxic and anti-inflammatory triterpenoids in the vines and leaves of Momordica charantia. Int J Mol Sci 2022;23:1071. DOI: https://doi.org/10.3390/ijms23031071

Zhao Q, Yin L, Zhang L, Jiang D, Liu L, Ji H. Chitoheptaose promotes heart rehabilitation in a rat myocarditis model by improving antioxidant, anti-inflammatory, and antiapoptotic properties. Oxid Med Cell Longev 2020;2020:2394704. DOI: https://doi.org/10.1155/2020/2394704

Osonoi S, Mizukami H, Itabashi C, Wada K, Kudoh K, Igawa A, et al. Increased oxidative stress underlies abnormal pain threshold in a normoglycemic Japanese population. Int J Mol Sci 2020;21:8306. DOI: https://doi.org/10.3390/ijms21218306

Wang L, Zhu L, Gong L, Zhang X, Wang Y, Liao J, et al. Effects of Activated charcoal-herb extractum complex on antioxidant status, lipid metabolites and safety of excess supplementation in weaned piglets. Animals (Basel) 2019;9:1151. DOI: https://doi.org/10.3390/ani9121151

Cao H, Yang B, Zhao Y, Deng X, Shen X. The pro-apoptosis and pro-inflammation role of LncRNA HIF1A-AS1 in Coxsackievirus B3-induced myocarditis via targeting miR-138. Cardiovasc Diagn Ther 2020;10:1245-55. DOI: https://doi.org/10.21037/cdt-20-545

Khodir A, Samra Y, Said E. A novel role of nifuroxazide in attenuation of sepsis-associated acute lung and myocardial injuries; role of TLR4/NLPR3/IL-1β signaling interruption. Life Sci 2020;256:117907. DOI: https://doi.org/10.1016/j.lfs.2020.117907

Wang C, Xu Y, Wang X, Guo C, Wang T, Wang Z. Dl-3-n-butylphthalide inhibits NLRP3 inflammasome and mitigates Alzheimer's-like pathology via Nrf2-TXNIP-TrX axis. Antioxid Redox Signal 2019;30:1411-31. DOI: https://doi.org/10.1089/ars.2017.7440

Wang B, Lim J, Kajikawa T, Li X, Vallance B, Moutsopoulos N, et al. Macrophage β2-integrins regulate IL-22 by ILC3s and protect from lethal Citrobacter rodentium-induced colitis. Cell Rep 2019;26:1614-26.e5. DOI: https://doi.org/10.1016/j.celrep.2019.01.054

Huang X, Liu W, Zhou Y, Sun M, Yang H, Zhang C, et al. Galectin-1 ameliorates lipopolysaccharide-induced acute lung injury via AMPK-Nrf2 pathway in mice. Free Radic Biol Med 2020;146:222-33. DOI: https://doi.org/10.1016/j.freeradbiomed.2019.11.011

Wang X, Wang Z, Wu H, Jia W, Teng L, Song J, et al. Sarcodon imbricatus polysaccharides protect against cyclophosphamide-induced immunosuppression via regulating Nrf2-mediated oxidative stress. Int J Biol Macromol 2018;120:736-44. DOI: https://doi.org/10.1016/j.ijbiomac.2018.08.157

Yang M, Mao G, Ouyang L, Shi C, Hu P, Huang S. Crocetin alleviates myocardial ischemia/reperfusion injury by regulating inflammation and the unfolded protein response. Mol Med Rep 2020;21:641-8. DOI: https://doi.org/10.3892/mmr.2019.10891

Huang K, Lin M, Hsu H, Hsu Y, Huang T, Lu I, et al. Pinocembrin reduces keratinocyte activation and ameliorates imiquimod-induced psoriasis-like dermatitis in BALB/c mice through the heme oxygenase-1/signal transducer and activator of Transcription 3 pathway. Evid Based Complement Alternat Med 2022;2022:7729836. DOI: https://doi.org/10.1155/2022/7729836

Yang J, Sun M, Yuan Q, Tang S, Dong M, Zhang R, et al. Keap1-Nrf2 signaling activation by Bardoxolone-methyl ameliorates high glucose-induced oxidative injury in human umbilical vein endothelial cells. Aging (Albany NY) 2020;12:10370-80. DOI: https://doi.org/10.18632/aging.103263

Ethics Approval

all animal experiments were performed according to the guidelines of laboratory animal care and were approved by the Animal Experimentation Ethics Committee of Zhejiang Eyong Pharmaceutical Research and Development Center, Hangzhou, China

Supporting Agencies

Huzhou Cardiovascular and Cerebrovascular Disease Discipline Group, Huzhou City Public Welfare Application Research Project

How to Cite

Shen, L., Lu, K., Chen, Z., Zhu, Y., Zhang, C., & Zhang, L. (2023). Pre-treatment with galectin-1 attenuates lipopolysaccharide-induced myocarditis by regulating the Nrf2 pathway . European Journal of Histochemistry, 67(4). https://doi.org/10.4081/ejh.2023.3816

Download Citation

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.

Pre-treatment with galectin-1 attenuates lipopolysaccharide-induced myocarditis by regulating the Nrf2 pathway

Authors