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Dose-Dependent Effects of Long-Term Administration of Hydrogen Sulfide on Myocardial Ischemia-Reperfusion Injury in Male Wistar Rats: Modulation of RKIP, NF-κB, and Oxidative Stress.
Int J Mol Sci. 2020 Feb 19; 21(4)IJ

Abstract

Decreased circulating levels of hydrogen sulfide (H2S) are associated with higher mortality following myocardial ischemia. This study aimed at determining the long-term dose-dependent effects of sodium hydrosulfide (NaSH) administration on myocardial ischemia-reperfusion (IR) injury. Male rats were divided into control and NaSH groups that were treated for 9 weeks with daily intraperitoneal injections of normal saline or NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg), respectively. At the end of the study, hearts from all rats were isolated and hemodynamic parameters were recorded during baseline and following IR. In isolated hearts, infarct size, oxidative stress indices as well as mRNA expression of H2S-, nitric oxide (NO)-producing enzymes, and inflammatory markers were measured. In heart tissue following IR, low doses of NaSH (0.28 and 0.56 mg/kg) had no effect, whereas an intermediate dose (1.6 mg/kg), improved recovery of hemodynamic parameters, decreased infarct size, and decreased oxidative stress. It also increased expression of cystathionine γ-lyase (CSE), Raf kinase inhibitor protein (RKIP), endothelial NO synthase (eNOS), and neuronal NOS (nNOS), as well as decreased expression of inducible NOS (iNOS) and nuclear factor kappa-B (NF-κB). At the high dose of 5.6 mg/kg, NaSH administration was associated with worse recovery of hemodynamic parameters and increased infarct size as well as increased oxidative stress. This dose also decreased expression of CSE, RKIP, and eNOS and increased expression of iNOS and NF-κB. In conclusion, chronic treatment with NaSH has a U-shaped concentration effect on IR injury in heart tissue. An intermediate dose was associated with higher CSE-derived H2S, lower iNOS-derived NO, lower oxidative stress, and inflammation in heart tissue following IR.

Authors+Show Affiliations

Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran.Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran.Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY 10031, USA.Department of Physiology and Pharmacology, Karolinska Institute, 17177 Stockholm, Sweden.Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32093102

Citation

Jeddi, Sajad, et al. "Dose-Dependent Effects of Long-Term Administration of Hydrogen Sulfide On Myocardial Ischemia-Reperfusion Injury in Male Wistar Rats: Modulation of RKIP, NF-κB, and Oxidative Stress." International Journal of Molecular Sciences, vol. 21, no. 4, 2020.
Jeddi S, Gheibi S, Kashfi K, et al. Dose-Dependent Effects of Long-Term Administration of Hydrogen Sulfide on Myocardial Ischemia-Reperfusion Injury in Male Wistar Rats: Modulation of RKIP, NF-κB, and Oxidative Stress. Int J Mol Sci. 2020;21(4).
Jeddi, S., Gheibi, S., Kashfi, K., Carlström, M., & Ghasemi, A. (2020). Dose-Dependent Effects of Long-Term Administration of Hydrogen Sulfide on Myocardial Ischemia-Reperfusion Injury in Male Wistar Rats: Modulation of RKIP, NF-κB, and Oxidative Stress. International Journal of Molecular Sciences, 21(4). https://doi.org/10.3390/ijms21041415
Jeddi S, et al. Dose-Dependent Effects of Long-Term Administration of Hydrogen Sulfide On Myocardial Ischemia-Reperfusion Injury in Male Wistar Rats: Modulation of RKIP, NF-κB, and Oxidative Stress. Int J Mol Sci. 2020 Feb 19;21(4) PubMed PMID: 32093102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dose-Dependent Effects of Long-Term Administration of Hydrogen Sulfide on Myocardial Ischemia-Reperfusion Injury in Male Wistar Rats: Modulation of RKIP, NF-κB, and Oxidative Stress. AU - Jeddi,Sajad, AU - Gheibi,Sevda, AU - Kashfi,Khosrow, AU - Carlström,Mattias, AU - Ghasemi,Asghar, Y1 - 2020/02/19/ PY - 2020/01/12/received PY - 2020/02/05/revised PY - 2020/02/14/accepted PY - 2020/2/26/entrez PY - 2020/2/26/pubmed PY - 2021/1/5/medline KW - H2S-producing enzymes KW - NF-κB KW - NO-producing enzymes KW - RKIP KW - hydrogen sulfide KW - infarct size KW - ischemia–reperfusion injury KW - nitric oxide KW - oxidative stress JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 4 N2 - Decreased circulating levels of hydrogen sulfide (H2S) are associated with higher mortality following myocardial ischemia. This study aimed at determining the long-term dose-dependent effects of sodium hydrosulfide (NaSH) administration on myocardial ischemia-reperfusion (IR) injury. Male rats were divided into control and NaSH groups that were treated for 9 weeks with daily intraperitoneal injections of normal saline or NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg), respectively. At the end of the study, hearts from all rats were isolated and hemodynamic parameters were recorded during baseline and following IR. In isolated hearts, infarct size, oxidative stress indices as well as mRNA expression of H2S-, nitric oxide (NO)-producing enzymes, and inflammatory markers were measured. In heart tissue following IR, low doses of NaSH (0.28 and 0.56 mg/kg) had no effect, whereas an intermediate dose (1.6 mg/kg), improved recovery of hemodynamic parameters, decreased infarct size, and decreased oxidative stress. It also increased expression of cystathionine γ-lyase (CSE), Raf kinase inhibitor protein (RKIP), endothelial NO synthase (eNOS), and neuronal NOS (nNOS), as well as decreased expression of inducible NOS (iNOS) and nuclear factor kappa-B (NF-κB). At the high dose of 5.6 mg/kg, NaSH administration was associated with worse recovery of hemodynamic parameters and increased infarct size as well as increased oxidative stress. This dose also decreased expression of CSE, RKIP, and eNOS and increased expression of iNOS and NF-κB. In conclusion, chronic treatment with NaSH has a U-shaped concentration effect on IR injury in heart tissue. An intermediate dose was associated with higher CSE-derived H2S, lower iNOS-derived NO, lower oxidative stress, and inflammation in heart tissue following IR. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/32093102/Dose_Dependent_Effects_of_Long_Term_Administration_of_Hydrogen_Sulfide_on_Myocardial_Ischemia_Reperfusion_Injury_in_Male_Wistar_Rats:_Modulation_of_RKIP_NF_κB_and_Oxidative_Stress_ L2 - https://www.mdpi.com/resolver?pii=ijms21041415 DB - PRIME DP - Unbound Medicine ER -