title: Mitochondrial aldehyde dehydrogenase activity protects against lipopolysaccharide‑induced cardiac dysfunction in rats.
abstract: Myocardial dysfunction in sepsis is associated with an increased risk of mortality. The mitochondrial aldehyde dehydrogenase (ALDH2) enzyme is crucial for protecting the heart from ischemic injury. The aim of the present study was to determine the role of ALDH2 in cardiac dysfunction induced by lipopolysaccharide (LPS). Male rats were treated intraperitoneally with LPS, and their stroke volume and cardiac output were evaluated using an M‑mode echocardiograph. The expression levels and activity of ALDH2, nitric oxide content and inducible nitric oxide synthase (iNOS) activity, and the opening of the mitochondrial permeability transition pore (MPTP) were also evaluated. Treatment with LPS (5, 10, or 20 mg/kg) resulted in a steady decrease in cardiac output and stroke volume. The ALDH2 activity was decreased in a dose‑dependent manner; however, the ALDH2 protein expression levels remained unchanged. Alda‑1, a specific activator of ALDH2, increased the activity of ALDH2 and lessened LPS‑induced cardiac dysfunction. A marked opening of the MPTP was observed 12 h following treatment with LPS, which was prevented by Alda‑1. The improvement in cardiac function in response to treatment with Alda‑1, was partially prevented by treatment with the MPTP inhibitor atractyloside. LPS treatment induced an increase in iNOS activation and inhibition of ALDH2 activity. The iNOS selective inhibitor, aminoguanidine, partially reversed the LPS‑induced ALDH2 activity decrease and MPTP opening. These results indicate that ALDH2 activity may have a role in protecting against LPS‑induced cardiac dysfunction. The potential mechanism may involve inhibition of MPTP opening and iNOS expression.
authors.affiliation: Department of Ultrasonography, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Jin-Bin
authors.initials: JB
authors.lastname: Yan
authors.affiliation: Department of Pharmacology, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Zheng
authors.affiliation: Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Xing-Hui
authors.initials: XH
authors.lastname: Song
authors.affiliation: Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Yue-Liang
authors.initials: YL
authors.lastname: Shen
authors.affiliation: Department of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Chen
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D001278:Atractyloside / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology; D004452:Echocardiography; D006146:Guanidines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001549:Benzamides; D052117:Benzodioxoles; D006146:Guanidines; D008070:Lipopolysaccharides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C531525:N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide; D001278:Atractyloside; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D000444:Aldehyde Dehydrogenase; C004479:pimagedine