Heart failure remains a significant global health burden, affecting millions and contributing to high morbidity and mortality. The pathophysiology of heart failure involves multiple mechanisms, among which oxidative stress plays a central role. Excessive production of reactive oxygen species (ROS) leads to cellular damage, inflammation, and apoptosis, particularly in cardiomyocytes. This study investigated the protective effects of N-acetylcysteine (NAC), a potent antioxidant, on oxidative stress, nuclear factor kappa B (NF-κB) activation, and cardiomyocyte apoptosis in an experimental model of doxorubicin-induced heart failure in Japanese white rabbits.
A total of 50 rabbits were used, with 10 serving as controls. Heart failure was induced by intravenous administration of doxorubicin at 1 mg/kg twice weekly for eight weeks. Rabbits developing heart failure were divided into two groups: 12 untreated (HF group) and 13 receiving daily oral NAC at 300 mg/kg for four weeks. Echocardiographic and hemodynamic assessments revealed significant impairments in cardiac function in the HF group, including increased left ventricular end-diastolic diameter (LVEDD) and pressure (LVEDP), reduced ejection fraction (EF), and diminished maximal and minimal rates of left ventricular pressure rise (+dp/dtmax and -dp/dtmin).Sugemalimab Formula These parameters improved significantly in the NAC-treated group, indicating enhanced cardiac performance.
Oxidative stress markers were markedly elevated in the HF group. Total antioxidant capacity (tAOC) in serum and myocardium was significantly reduced, while levels of 8-iso-prostaglandin F2 (8-iso-PGF2), a reliable indicator of lipid peroxidation, were substantially increased. Glutathione (GSH) levels were also decreased in the HF group. NAC treatment effectively restored tAOC and GSH levels and significantly reduced 8-iso-PGF2 concentrations, demonstrating its ability to enhance antioxidant defenses and reduce oxidative damage.
Apoptosis was assessed using the TUNEL assay. The apoptotic index was significantly higher in the HF group compared to controls, and this increase was attenuated by NAC treatment. Immunohistochemical analysis showed upregulated expression of pro-apoptotic Bax and downregulated anti-apoptotic Bcl-2 in the HF group, resulting in a decreased Bcl-2/Bax ratio. NAC reversed these changes, promoting cell survival. Western blot analysis confirmed increased NF-κBp65 expression and activity in the HF group, associated with elevated inducible nitric oxide synthase (iNOS) levels and reduced phosphorylation of IκB-α.Ixekizumab Autophagy NAC treatment normalized these protein expressions, suggesting inhibition of NF-κB activation.PMID:34473924
Correlation analyses revealed that myocardial apoptosis was positively correlated with LVEDP, NF-κBp65 expression, and 8-iso-PGF2 levels, but negatively correlated with +dp/dtmax, -dp/dtmin, and the Bcl-2/Bax ratio. These findings highlight the interplay between oxidative stress, inflammatory signaling, and cell death in heart failure progression.
In conclusion, N-acetylcysteine exerts significant cardioprotective effects in a rabbit model of heart failure by reducing oxidative stress, suppressing NF-κB activation, and inhibiting cardiomyocyte apoptosis. These results support the potential therapeutic value of antioxidants like NAC in mitigating structural and functional deterioration in heart failure, although further clinical validation is warranted.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com