Histological and Immunohistochemical Study of the Potential Protective Effect of N-Acetylcysteine Against Sorafenib Induced Cardiotoxicity in Adult Male Albino Rats | ||
| Egyptian Journal of Histology | ||
| Articles in Press, Accepted Manuscript, Available Online from 25 February 2025 | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejh.2025.347269.2187 | ||
| Author | ||
| Dalia El-sayed El-ghazouly* | ||
| Histology Department, Faculty of Medicine, Menoufia University, Shibin El-kom, Egypt | ||
| Abstract | ||
| Background: Sorafenib (SOR) is a tyrosine kinase inhibitor currently being used to treat hepatocellular and renal cell carcinoma. However, its use is associated with some serious cardiovascular adverse effects. N-acetylcysteine (NAC) is a well-known medication with potent antioxidant and anti-inflammatory features. Aim: The work's goal was to explore the probable protective impact of N-acetylcysteine on sorafenib-induced cardiotoxicity in rats. Materials and Methods: Forty adult male albino rats were equally classified into four groups: Group I (Control), group II (NAC): Received N-Acetylcysteine 200mg/kg/day, group III (SOR): Received sorafenib 100 mg/kg/day, group IV (SOR + NAC): Received N-Acetylcysteine and sorafenib using the identical dosages as earlier groups. For four weeks, the medication was administered once daily. At the end of this experiment, blood samples were gathered for biochemical study of serum malondialdehyde and glutathione. Heart samples were gathered and provided for histological study using Hematoxylin and Eosin, Masson's trichrome stains and immunohistochemical study using Glutathione peroxidase 4 (GPx4) and Tumor necrosis factor-alpha (TNF-α). Electron microscopic examination was done. Studies using morphometrics and statistics were conducted. Results: Groups I and II revealed normal histological and immunohistochemical results. Sorafenib treated group (III) revealed severe alterations in myocardium. There was marked distortion and fragmentation of cardiac muscle fibers which appeared with shrunken pyknotic nuclei and lost striations. Massive inflammatory cell infiltration and collagen deposition were seen between the muscle fibers and around dilated congested blood vessels. Ultrastructural observations revealed fragmented myofibrils with loss of banding pattern and swollen mitochondria with destructed cristae. Highly Significant decline in GPx4 immunoreactivity and rise in TNF-α immunoreactivity were also noticed. Highly significant changes in serum malondialdehyde and glutathione levels were detected. N-Acetylcysteine administration with sorafenib in group IV minimized these changes. Conclusion: N-Acetylcysteine can be a promising protective agent for alleviating sorafenib-induced cardiotoxicity through its antioxidant and anti-inflammatory effects. | ||
| Keywords | ||
| Key Words: Sorafenib; N-Acetylcysteine; Cardiac muscle; GPx4; TNF-α | ||
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