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Tytuł:
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Ergosterol Attenuates LPS-Induced Myocardial Injury by Modulating Oxidative Stress and Apoptosis in Rats.
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Autorzy:
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Xu J; Burn Wound Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Lin C; Burn Wound Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Wang T; Department of Infectious Internal Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Zhang P; Burn Wound Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Liu Z; Burn Wound Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Lu C; Burn Wound Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
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Źródło:
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Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2018; Vol. 48 (2), pp. 583-592. Date of Electronic Publication: 2018 Jul 18.
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Typ publikacji:
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Journal Article; Retracted Publication
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Język:
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English
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Imprint Name(s):
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Publication: 2019- : Düsseldorf, Germany : Cell Physiol Biochem Press GmbH & Co KG
Original Publication: Basel ; New York : S. Karger, 1991-2018.
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MeSH Terms:
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Apoptosis/*drug effects
Ergosterol/*pharmacology
Lipopolysaccharides/*toxicity
Oxidative Stress/*drug effects
Animals ; Apoptosis Regulatory Proteins/metabolism ; Cell Line ; Cell Survival/drug effects ; Creatine Kinase, MB Form/metabolism ; Ergosterol/chemistry ; Male ; Malondialdehyde/metabolism ; Myocardium/metabolism ; Myocardium/pathology ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; NF-E2-Related Factor 2/antagonists & inhibitors ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; RNA Interference ; RNA, Small Interfering/metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction/drug effects ; Superoxide Dismutase/metabolism
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Contributed Indexing:
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Keywords: Apoptosis; Ergosterol; Myocardial injury; Oxidative stress; Sepsis
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Substance Nomenclature:
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0 (Apoptosis Regulatory Proteins)
0 (Lipopolysaccharides)
0 (NF-E2-Related Factor 2)
0 (Nfe2l2 protein, rat)
0 (RNA, Small Interfering)
4Y8F71G49Q (Malondialdehyde)
EC 1.15.1.1 (Superoxide Dismutase)
EC 2.7.3.2 (Creatine Kinase, MB Form)
Z30RAY509F (Ergosterol)
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Entry Date(s):
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Date Created: 20180719 Date Completed: 20180918 Latest Revision: 20230912
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Update Code:
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20240105
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DOI:
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10.1159/000491887
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PMID:
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30021198
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Background/aims: Ergosterol (ER) is the primary sterol found in fungi and is named after the ergot fungus. A variety of pharmacological activities have been reported for ER, including antioxidative, anti-proliferative, and anti-inflammatory effects, although its role in sepsis remains unclear.
Methods: The protective effect of ER on lipopolysaccharide (LPS)-induced sepsis myocardial injury was evaluated both in vivo and in vitro. Rats were pretreated with ER and then with LPS. Histopathology of heart tissues was first performed. Subsequently, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), creatine kinase MB fraction (CK-MB), and lactate dehydrogenase (LDH) in serum and heart tissues were assessed by enzyme-linked immunosorbent assay kits. Western blotting was further used to evaluate the expression of antioxidant proteins (HO-1 and cytochrome c) and apoptosis associated proteins (Bcl-2, Bax, cleaved-caspase-3, cleaved-caspase-9, and cleaved-PARP). In addition, the effects of ER on oxidative stress biomarkers and apoptosis proteins were also detected in LPS-treated H9C2 cells. Moreover, small interfering Nrf2 RNA was transfected to H9C2 cells to study the role of Nrf2 signaling in connection with the protective effects of ER.
Results: Pretreatment with ER ameliorated the histopathological changes in heart tissue induced by LPS injection, increased SOD activity, and reduced MDA content, and CK-MB and LDH levels. Furthermore, ER restored the expression of Nrf-2 and HO-1 in rat hearts, attenuating apoptotic damage via up-regulation of Bcl-2 in combination with the inhibition of Bax, cytochrome c, cleaved-caspase-3 and 9, and PARP, as revealed by western blot. When Nrf2 was blocked by siRNA, the effects of ER on SOD and MDA activity, as well as the expression of the antioxidant proteins and apoptosis-associated proteins were abolished.
Conclusions: We demonstrated that ER has a cardioprotective effect in LPS-induced sepsis model through modulation of the antioxidant activity and anti-apoptosis effects and this process might be regulated by Nrf2 signaling.
(© 2018 The Author(s). Published by S. Karger AG, Basel.)
Retraction in: Cell Physiol Biochem. 2023 Aug 31;57(4):314. (PMID: 37697994)
