Author:
Alwaili Maha Abdullah,Abu-Almakarem Amal S.,El-Said Karim Samy,Eid Thamir M.,Mobasher Maysa A.,Alsabban Ashwaq Hassan,Alburae Najla Ali,Banjabi Abeer A.,Soliman Mohamed Mostafa
Abstract
Abstract
Doxorubicin (DOX) is used to treat a variety of malignancies; however, its cardiotoxicity limits its effectiveness. Shikimic acid (SA) showed several promising biomedical applications. This study investigated the protective effect of SA on DOX-induced cardiotoxicity in male rats. The ADMETlab 2.0 web server was used to predict the pharmacokinetic properties of SA. Molecular docking studies were conducted using AutoDock Vina. Fifty male rats were divided into 4 groups (n = 10); G1 was a negative control; G2 was injected with 4 mg/kg of DOX intraperitoneally (i.p.) once a week for a month; G3 was gavaged by 1/10 of SA LD50 (280 mg/kg) daily for a month, and G4 was injected with DOX as in G2 and with SA as in G3. After a month, hematological, biochemical, molecular, and histopathological investigations were assessed. The results showed that SA treatment led to significant amelioration of the DOX-induced cardiotoxicity in rats by restoring hematological, biochemical, inflammatory biomarkers, antioxidant gene expression, and cardiac histopathological alterations. Importantly, the impact of SA treatment against DOX-promoted cardiac deterioration is by targeting the Nrf-2/Keap-1/HO-1/NQO-1 signaling pathway, which in turn induces the antioxidant agents. These findings suggest that SA treatment could potentially mitigate cardiac toxicity during DOX-based chemotherapy.
Publisher
Springer Science and Business Media LLC
Reference72 articles.
1. Anand, U. et al. Cancer chemotherapy and beyond: current status, drug candidates, associated risks, and progress in targeted therapeutics. Genes Dis. 10, 1367–1401 (2022).
2. Voulgari, A. & Pintzas, A. Epithelial–mesenchymal transition in cancer metastasis: mechanisms, markers, and strategies to overcome drug resistance in the clinic. Biochim. Biophys. Acta 1796, 75–90 (2009).
3. Yu, L. R. & Desai, V. G. Doxorubicin cardiotoxicity: preclinical and clinical circulating protein markers. In Biomarkers in Toxicology. Biomarkers in Disease: Methods, Discoveries and Applications (eds Patel, V. B., Preedy, V. R. & Rajendram, R.) 1–27 (Springer, 2022).
4. Trapani, D. et al. Management of cardiac toxicity induced by chemotherapy. J. Clin. Med. 9, 2885 (2020).
5. Al-Taee, H. et al. β-caryophyllene, a dietary phytocannabinoid attenuates oxidative stress, inflammation, apoptosis and prevents structural alterations of the myocardium against doxorubicin-induced acute cardiotoxicity in rats: an in vitro and in vivo study. Eur. J. Pharmacol. 858, 172467 (2019).
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献