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Rosuvastatin (RSV) and carvedilol (CAR) were given for 7 consecutive days with concurrent administration of two doses of isoprenaline (ISP) on 6th and 7th days to induce MI. Isoprenaline injections caused detrimental alterations in the myocardial architecture and electrocardiogram (ECG) pattern and significantly increased the infarct size, heart index and serum levels of cardiotoxicity markers compared to the control group. ISP induced oxidative damage, inflammatory and apoptotic events and downregulated PI3K\/Akt\/Nrf2\/HO\u20101\u00a0signalling pathway compared to the control values. Treatment with low\u2010dose CAR and\/or RSV prevented the ECG and histopathological alterations induced by ISP, and also reduced the infarct size, heart index, serum creatine kinase\u2010MB, cardiac troponin\u2010I and C\u2010reactive protein levels compared to ISP group. CAR and\/or RSV treatment restored the activity of superoxide dismutase and total antioxidant capacity with a consequent reduction in lipid peroxides level. Further, they decreased the expression of nuclear factor (NF)\u2010\u03baB (p65) and increased the phosphorylated PI3K and Akt, which may activate the anti\u2010apoptotic signalling as evidenced by the decreased active caspase 3\u00a0level. The combination therapy has a more significant effect in the most studied parameters than their monotherapy, which may be because of the activation of PI3K\/Akt Nrf2\/HO\u20101 pro\u2010survival signalling pathway. This study highlights the potential benefits of combining RSV with low\u2010dose CAR in case of MI.<\/jats:p>","DOI":"10.1111\/1440-1681.13535","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T22:43:59Z","timestamp":1622760239000},"page":"1358-1370","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Rosuvastatin and low\u2010dose carvedilol combination protects against isoprenaline\u2010induced myocardial infarction in rats: Role of PI3K\/Akt\/Nrf2\/HO\u20101 signalling"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1908-2347","authenticated-orcid":false,"given":"Sarah A.","family":"Baraka","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Department Faculty of Pharmacy Ahram Canadian University 6th of October City Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai 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