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Article

Identification of Lactate as a Cardiac Protectant by Inhibiting Inflammation and Cardiac Hypertrophy Using a Zebrafish Acute Heart Failure Model

1
Biology Department, University of Wisconsin-River Falls, River Falls, WI 54022, USA
2
Department of Chinese Pharmaceutical Sciences and Chines Medicine Resources, China Medical University, Taichung 40402, Taiwan
3
Master Program for Food and Drug Safety, China Medical University, Taichung 40402, Taiwan
*
Authors to whom correspondence should be addressed.
Academic Editors: Yuhei Nishimura and Mary Meegan
Pharmaceuticals 2021, 14(3), 261; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030261
Received: 20 January 2021 / Revised: 7 March 2021 / Accepted: 9 March 2021 / Published: 15 March 2021
(This article belongs to the Special Issue Zebrafish as a Powerful Tool for Drug Discovery 2021)
Acute heart failure (AHF) commonly arises from decompensated chronic heart failure or sudden structural and functional breakdown causing a decrease in cardiac contractility and consequently fluid accumulation and systemic congestion. Current treatment for AHF aims at reducing fluid overload and improving hemodynamic which results in quick symptom relief but still poor prognostic outcome. This study utilizes a zebrafish AHF model induced by aristolochic acid (AA) to look for natural products that could attenuate the progression of AHF. The project started off by testing nearly seventy herbal crude extracts. Two of the positive extracts were from Chinese water chestnuts and are further studied in this report. After several rounds of chromatographical chemical fractionation and biological tests, a near pure fraction, named A2-4-2-4, with several hydrophilic compounds was found to attenuate the AA-induced AHF. A2-4-2-4 appeared to inhibit inflammation and cardiac hypertrophy by reducing MAPK signaling activity. Chemical analyses revealed that the major compound in A2-4-2-4 is actually lactate. Pure sodium lactate showed attenuation of the AA-induced AHF and inflammation and cardiac hypertrophy suppression as well, suggesting that the AHF attenuation ability in A2-4-2-4 is attributable to lactate. Our studies identify lactate as a cardiac protectant and a new therapeutic agent for AHF. View Full-Text
Keywords: acute heart failure; zebrafish; lactate; inflammation; cardiac hypertrophy acute heart failure; zebrafish; lactate; inflammation; cardiac hypertrophy
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MDPI and ACS Style

Haege, E.R.; Huang, H.-C.; Huang, C.-c. Identification of Lactate as a Cardiac Protectant by Inhibiting Inflammation and Cardiac Hypertrophy Using a Zebrafish Acute Heart Failure Model. Pharmaceuticals 2021, 14, 261. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030261

AMA Style

Haege ER, Huang H-C, Huang C-c. Identification of Lactate as a Cardiac Protectant by Inhibiting Inflammation and Cardiac Hypertrophy Using a Zebrafish Acute Heart Failure Model. Pharmaceuticals. 2021; 14(3):261. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030261

Chicago/Turabian Style

Haege, Elijah R., Hui-Chi Huang, and Cheng-chen Huang. 2021. "Identification of Lactate as a Cardiac Protectant by Inhibiting Inflammation and Cardiac Hypertrophy Using a Zebrafish Acute Heart Failure Model" Pharmaceuticals 14, no. 3: 261. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030261

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