<i>N</i>-Acetylcysteine Treatment Restores the Protective Effect of Heart Ischemic Postconditioning in a Murine Model in the Early Stages of Atherosclerosis
<b>Background/Objectives:</b> Ischemic postconditioning (IP) is a well-established intervention that mitigates this damage by activating endogenous cardioprotective pathways. However, the presence of comorbidities such as dyslipidemia can disrupt these protective mechanisms and abolish t...
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2025-07-01
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| author | Tamara Zaobornyj Virginia Perez Georgina Ossani Tamara Mazo Eugenia Godoy Jorge Godoy Yohana Yanaje Camila Musci-Ferrari Mario Contin Valeria Tripodi Magali Barchuk Gabriela Berg Ricardo J. Gelpi Martin Donato Veronica D’Annunzio |
| author_facet | Tamara Zaobornyj Virginia Perez Georgina Ossani Tamara Mazo Eugenia Godoy Jorge Godoy Yohana Yanaje Camila Musci-Ferrari Mario Contin Valeria Tripodi Magali Barchuk Gabriela Berg Ricardo J. Gelpi Martin Donato Veronica D’Annunzio |
| author_sort | Tamara Zaobornyj |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Ischemic postconditioning (IP) is a well-established intervention that mitigates this damage by activating endogenous cardioprotective pathways. However, the presence of comorbidities such as dyslipidemia can disrupt these protective mechanisms and abolish the infarct-sparing effect typically induced by IP. In this context, identifying pharmacological strategies to restore cardioprotection is of clinical relevance. This study aimed to evaluate whether <i>N</i>-acetylcysteine (NAC), a glutathione precursor with antioxidant properties, can restore the infarct-limiting effect of IP compromised by HFD-induced oxidative stress. <b>Methods:</b> Male mice were fed a control diet (CD) or HFD for 12 weeks. NAC (10 mM) was administered in drinking water for 3 weeks before ex vivo myocardial ischemia/reperfusion (I/R) injury (30 min ischemia/60 min reperfusion). In IP groups, six cycles of brief I/R were applied at the onset of reperfusion. Infarct size, ventricular function, redox status (GSH/GSSG), lipid profile, and histology were evaluated. <b>Results:</b> NAC improved the lipid profile (HDL/non-HDL ratio) and enhanced the infarct-sparing effect of IP in CD-fed mice. In HFD-fed mice, NAC restored the efficacy of IP, significantly reducing infarct size (HFD-I/R-NAC: 39.7 ± 4.5% vs. HFD-IP-NAC: 26.4 ± 2.0%, <i>p</i> < 0.05) without changes in ventricular function. The ratio of oxidized/reduced glutathione (GSSG/GSH) is depicted. Under basal conditions, the hearts of mice fed an HFD exhibited a shift towards a more oxidized state compared to the control diet CD group. In the I/R protocol, a significant shift towards a more oxidized state was observed in both CD and HFD-fed animals. In the IP protocol, the GSSG/GSH ratio revealed a tendency to basal values in comparison to the I/R protocol. The analysis indicates that animals subjected to I/R and IP protocols in conjunction with NAC show a tendency to reach basal values, thus suggesting a potential for the reduction in ROS. <b>Conclusions:</b> NAC treatment mitigates oxidative stress and restores the cardioprotective effect of ischemic postconditioning in a model of early-stage atherosclerosis. These findings support NAC as a potential adjunct therapy to improve myocardial resistance to reperfusion injury under dyslipidemic conditions |
| format | Article |
| id | doaj-art-c212bb8ad9f942a8bfd16426f3e5f460 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-c212bb8ad9f942a8bfd16426f3e5f4602025-08-20T03:56:49ZengMDPI AGPharmaceuticals1424-82472025-07-01187101410.3390/ph18071014<i>N</i>-Acetylcysteine Treatment Restores the Protective Effect of Heart Ischemic Postconditioning in a Murine Model in the Early Stages of AtherosclerosisTamara Zaobornyj0Virginia Perez1Georgina Ossani2Tamara Mazo3Eugenia Godoy4Jorge Godoy5Yohana Yanaje6Camila Musci-Ferrari7Mario Contin8Valeria Tripodi9Magali Barchuk10Gabriela Berg11Ricardo J. Gelpi12Martin Donato13Veronica D’Annunzio14Instituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaInstituto de Fisiopatología Cardiovascular (INFICA), Facultad de Ciencias Médicas, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaDepartamento de Patología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Fisiopatología Cardiovascular (INFICA), Facultad de Ciencias Médicas, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Fisiopatología Cardiovascular (INFICA), Facultad de Ciencias Médicas, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Fisiopatología Cardiovascular (INFICA), Facultad de Ciencias Médicas, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Fisiopatología Cardiovascular (INFICA), Facultad de Ciencias Médicas, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Bioquímica y Medicina Molecular (IBIMOL UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaDepartamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaDepartamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Cátedra de Bioquímica Clínica I, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Cátedra de Bioquímica Clínica I, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Fisiopatología Cardiovascular (INFICA), Facultad de Ciencias Médicas, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Fisiopatología Cardiovascular (INFICA), Facultad de Ciencias Médicas, Universidad de Buenos Aires, Buenos Aires 1114, ArgentinaInstituto de Fisiopatología Cardiovascular (INFICA), Facultad de Ciencias Médicas, Universidad de Buenos Aires, Buenos Aires 1114, Argentina<b>Background/Objectives:</b> Ischemic postconditioning (IP) is a well-established intervention that mitigates this damage by activating endogenous cardioprotective pathways. However, the presence of comorbidities such as dyslipidemia can disrupt these protective mechanisms and abolish the infarct-sparing effect typically induced by IP. In this context, identifying pharmacological strategies to restore cardioprotection is of clinical relevance. This study aimed to evaluate whether <i>N</i>-acetylcysteine (NAC), a glutathione precursor with antioxidant properties, can restore the infarct-limiting effect of IP compromised by HFD-induced oxidative stress. <b>Methods:</b> Male mice were fed a control diet (CD) or HFD for 12 weeks. NAC (10 mM) was administered in drinking water for 3 weeks before ex vivo myocardial ischemia/reperfusion (I/R) injury (30 min ischemia/60 min reperfusion). In IP groups, six cycles of brief I/R were applied at the onset of reperfusion. Infarct size, ventricular function, redox status (GSH/GSSG), lipid profile, and histology were evaluated. <b>Results:</b> NAC improved the lipid profile (HDL/non-HDL ratio) and enhanced the infarct-sparing effect of IP in CD-fed mice. In HFD-fed mice, NAC restored the efficacy of IP, significantly reducing infarct size (HFD-I/R-NAC: 39.7 ± 4.5% vs. HFD-IP-NAC: 26.4 ± 2.0%, <i>p</i> < 0.05) without changes in ventricular function. The ratio of oxidized/reduced glutathione (GSSG/GSH) is depicted. Under basal conditions, the hearts of mice fed an HFD exhibited a shift towards a more oxidized state compared to the control diet CD group. In the I/R protocol, a significant shift towards a more oxidized state was observed in both CD and HFD-fed animals. In the IP protocol, the GSSG/GSH ratio revealed a tendency to basal values in comparison to the I/R protocol. The analysis indicates that animals subjected to I/R and IP protocols in conjunction with NAC show a tendency to reach basal values, thus suggesting a potential for the reduction in ROS. <b>Conclusions:</b> NAC treatment mitigates oxidative stress and restores the cardioprotective effect of ischemic postconditioning in a model of early-stage atherosclerosis. These findings support NAC as a potential adjunct therapy to improve myocardial resistance to reperfusion injury under dyslipidemic conditionshttps://www.mdpi.com/1424-8247/18/7/1014ischemia/reperfusion injuryischemic postconditioninghigh-fat dietredox balance<i>N</i>-acetylcysteine |
| spellingShingle | Tamara Zaobornyj Virginia Perez Georgina Ossani Tamara Mazo Eugenia Godoy Jorge Godoy Yohana Yanaje Camila Musci-Ferrari Mario Contin Valeria Tripodi Magali Barchuk Gabriela Berg Ricardo J. Gelpi Martin Donato Veronica D’Annunzio <i>N</i>-Acetylcysteine Treatment Restores the Protective Effect of Heart Ischemic Postconditioning in a Murine Model in the Early Stages of Atherosclerosis Pharmaceuticals ischemia/reperfusion injury ischemic postconditioning high-fat diet redox balance <i>N</i>-acetylcysteine |
| title | <i>N</i>-Acetylcysteine Treatment Restores the Protective Effect of Heart Ischemic Postconditioning in a Murine Model in the Early Stages of Atherosclerosis |
| title_full | <i>N</i>-Acetylcysteine Treatment Restores the Protective Effect of Heart Ischemic Postconditioning in a Murine Model in the Early Stages of Atherosclerosis |
| title_fullStr | <i>N</i>-Acetylcysteine Treatment Restores the Protective Effect of Heart Ischemic Postconditioning in a Murine Model in the Early Stages of Atherosclerosis |
| title_full_unstemmed | <i>N</i>-Acetylcysteine Treatment Restores the Protective Effect of Heart Ischemic Postconditioning in a Murine Model in the Early Stages of Atherosclerosis |
| title_short | <i>N</i>-Acetylcysteine Treatment Restores the Protective Effect of Heart Ischemic Postconditioning in a Murine Model in the Early Stages of Atherosclerosis |
| title_sort | i n i acetylcysteine treatment restores the protective effect of heart ischemic postconditioning in a murine model in the early stages of atherosclerosis |
| topic | ischemia/reperfusion injury ischemic postconditioning high-fat diet redox balance <i>N</i>-acetylcysteine |
| url | https://www.mdpi.com/1424-8247/18/7/1014 |
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