Sains Malaysiana 50(4)(2021): 945-952

http://doi.org/10.17576/jsm-2021-5004-06

 

Grape Seed Proanthocyanidin Improves Lipopolysaccharide-Induced Myocardial Toxicity in Mice

(Proantosianidin Biji AnggurMenambahbaik Ketoksikan Miokardium pada Tikus yang Diaruh Lipopolisakarida)

 

LIU XIANCHU1,2, LI SHA1, CHEN RUYAN1, LI YUE1, PENG HUAN3 & LIU MING1*

 

1Department of Human Movement Science, Institute of Physical Culture, Hunan University of Arts and Science, 415000 Changde, Hunan, People’s Republic of China

 

2Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, Hunan Normal University, 410081 Changsha, People’s Republic of China

 

3Department of Hematology, Xiangya Changde Hospital, 415000 Changde, Hunan, People’s Republic of China

 

Diserahkan: 16 Mei 2019/Diterima: 15 September 2020

 

ABSTRACT

Lipopolysaccharide (LPS) is an important pathogenic factor for sepsis which results in cardiovascular diseases and even mortality. Proanthocyanidin, one of the main components in grape seed, has a wide range of biological activities in various diseases. The mouse model was established by intraperitoneal injection with LPS. Grape seed proanthocyanidin (GSP) was administered continuously for 8 days. Our results showed that pre-treatment of GSP dramatically ameliorated the level of creatine kinase (CK) and lactate dehydrogenase (LDH) to defend against LPS-induced myocardial toxicity (p<0.01). Moreover, pre-treatment of GSP significantly mitigated the expression of matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9) to inhibit LPS-induced myocardial fibrosis (p<0.01). In addition, pre-treatment of GSP significantly increased superoxide dismutase (SOD) and catalase (CAT) activities to improve the level of malondialdehyde (MDA) and hydrogen peroxide (H2O2) (p<0.01). Lastly, pre-treatment of GSP relieved tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) activities to prevent inflammatory responses (p<0.01).

 

Keywords: Anti-inflammatory; anti-oxidant; grape seed proanthocyanidin; heart; lipopolysaccharide

 

ABSTRAK

Lipopolisakarida (LPS) adalah faktor patogen penting untuk sepsis yang mengakibatkan penyakit kardiovaskular dan juga kematian. Proantosianidin iaitu salah satu komponen utama dalam biji anggur mempunyai julat aktiviti biologi yang luas dalam pelbagai penyakit. Model tikus dibangunkan melalui suntikan intraperitoneum menggunakan LPS. Proantosianidin biji anggur (GSP) diberikan secara berterusan selama 8 hari. Hasil kajian kami menunjukkan bahawa pra-rawatan GSP meningkatkan tahap kreatina kinase (CK) dan laktat dehidrogenase (LDH) dengan secara dramatik untuk mempertahankan diri terhadap ketoksikan miokardium yang diaruh oleh LPS (p <0.01). Tambahan pula, pra-rawatan GSP secara signifikan mengurangkan pengekspresan matriks metallopeptida 2 (MMP-2) dan matriks metallopeptida 9 (MMP-9) dengan signifikan untuk menghalang fibrosis miokardium yang diaruh LPS (p <0.01). Di samping itu, pra-rawatan GSP meningkatkan aktiviti superoksida dismutase (SOD) dan katalase (CAT) dengan signifikan untuk meningkatkan tahap malondialdehida (MDA) dan hidrogen peroksida (H2O2) (p <0.01). Akhir sekali, pra-rawatan GSP menekan aktiviti faktor nekrosis tumor alfa (TNF-α) dan interleukin 6 (IL-6) untuk mencegah tindak balas keradangan (p <0.01).

 

Kata kunci: Anti-oksidan; anti-radang; jantung; lipopolisakarida; proantosianidin biji anggur

 

RUJUKAN

Bagchi, D., Garg, A., Krohn, R.L., Bagchi, M., Bagchi, D.J., Balmoori, J. & Stohs, S.J. 1998. Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice. General Pharmacology: The Vascular System 30(5): 771-776.

Bai, T., Hu, X., Zheng, Y., Wang, S., Kong, J. & Cai, L. 2016. Resveratrol protects against lipopolysaccharide-induced cardiac dysfunction by enhancing SERCA2a activity through promoting the phospholamban oligomerization. American Journal of Physiology-Heart and Circulatory Physiology 311(4): H1051-H1062.

Boghdady, N.A.E. 2013. Antioxidant and antiapoptotic effects of proanthocyanidin and ginkgo biloba extract against doxorubicin-induced cardiac injury in rats. Cell Biochemistry & Function 31(4): 344-351.

Chagnon, F., Metz, C.N., Bucala, R. & Lesur, O. 2005. Endotoxin-induced myocardial dysfunction: Effects of macrophage migration inhibitory factor neutralization. Circulation Research 96(10): 1095-1102.

Court, O., Kumar, A., Parrillo, J.E. & Kumar, A. 2002. Clinical review: Myocardial depression in sepsis and septic shock. Critical Care 6(6): 500-508.

Demirkaya, E., Avci, A., Kesik, V., Karslioglu, Y., Oztas, E., Kismet, E., Gokcay, E., Durak, I. & Koseoglu, V. 2009. Cardioprotective roles of aged garlic extract, grape seed proanthocyanidin, and hazelnut on doxorubicin-induced cardiotoxicity. Canadian Journal of Physiology & Pharmacology 87(8): 633-640.

Elias, R.J., Kellerby, S.S. & Decker, E.A. 2008. Antioxidant activity of proteins and peptides. Critical Reviews in Food Science and Nutrition 48(5): 430-441.

Goraca, A., Piechota, A. & Huk-Kolega, H. 2009. Effect of alpha-lipoic acid on LPS-induced oxidative stress in the heart. Journal of Physiology and Pharmacology 60(1): 61-68.

He, H., Chang, X., Gao, J., Zhu, L., Miao, M. & Yan, T. 2015. Salidroside mitigates sepsis-induced myocarditis in rats by regulating IGF-1/PI3K/Akt/GSK-3β signaling. Inflammation 38(6): 2178-2184.

Houde, V., Grenier, D. & Chandad, F. 2006. Protective effects of grape seed proanthocyanidins against oxidative stress induced by lipopolysaccharides of periodontopathogens. Journal of Periodontology 77(8): 1371-1379.

Lew, W.Y., Bayna, E., Molle, E.D., Contu, R., Condorelli, G. & Tang, T. 2014. Myocardial fibrosis induced by exposure to subclinical lipopolysaccharide is associated with decreased miR-29c and enhanced NOX2 expression in mice. PLoS ONE 9(9): e107556.

Lew, W.Y., Bayna, E., Molle, E.D., Dalton, N.D., Lai, N.C., Bhargava V., Mendiola, V., Clopton, P. & Tang, T. 2013. Recurrent exposure to subclinical lipopolysaccharide increases mortality and induces cardiac fibrosis in mice. PLoS ONE 8(4): e61057.

Li, F., Lang, F., Zhang, H., Xu, L., Wang, Y. & Hao, E. 2016. Role of TFEB mediated autophagy, oxidative stress, inflammation, and cell death in endotoxin induced myocardial toxicity of young and aged mice. Oxidative Medicine & Cellular Longevity 2016: 5380319.

Li, J., Li, J., Li, S., He, B., Mi, Y., Cao, H., Zhang, C. & Li, L. 2012. Ameliorative effect of grape seed proanthocyanidin extract on thioacetamide-induced mouse hepatic fibrosis. Toxicology Letters 213(3): 353-360.

Long, M., Zhang, Y., Li, P., Yang, S.H., Zhang, W.K., Han, J.X., Wang, Y. & He, J.B. 2016. Intervention of grape seed proanthocyanidin extract on the subchronic immune injury in mice induced by aflatoxin B1. International Journal of Molecular Sciences 17(4): 516.

Mansouri, E., Khorsandi, L. & Abdollahzade, F.A. 2015. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats. Veterinary Research Forum 6(2): 119-124.

Minasyan, H. 2017. Sepsis and septic shock: Pathogenesis and treatment perspectives. Journal of Critical Care 40: 229-242.

Polat, G., Ugan, R.A., Cadirci, E. & Halici, Z. 2017. Sepsis and septic shock: Current treatment strategies and new approaches. Eurasian Journal of Medicine 49(1): 53-58.

Suzuki, T., Suzuki, Y., Okuda, J., Kurazumi, T., Suhara, T., Ueda, T., Nagata, H. & Morisaki, H. 2017. Sepsis-induced cardiac dysfunction and β-adrenergic blockade therapy for sepsis. Journal of Intensive Care 5(1): 22.

Wang, Z., Wu, G., Liu, H., Xing, N., Sun, Y., Zhai, Y., Yang, B., Kong, A.N., Kuang, H. & Wang, Q. 2017a. Cardioprotective effect of the xanthones from Gentianella acuta against myocardial ischemia/reperfusion injury in isolated rat heart. Biomedicine & Pharmacotherapy 93: 626-635.

Wang, F., Jin, Z., Shen, K., Weng, T., Chen, Z., Feng, J., Zhang, Z., Liu, J., Zhang, X. & Chu, M. 2017b. Butyrate pretreatment attenuates heart depression in a mice model of endotoxin-induced sepsis via anti-inflammation and anti-oxidation. The American Journal of Emergency Medicine 35(3): 402-409.

Zhao, P., Wang, Y., Zeng, S., Lu, J., Jiang, T.M. & Li, Y.M. 2015. Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice. Immunopharmacology and Immunotoxicology 37(5): 428-433.

 

*Pengarang untuk surat-menyurat; email: liuminghappy36@163.com

   

 

 

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