Esculetin improves gut dysbiosis in isoproterenol-induced myocardial infarction in male rats
DOI:
https://doi.org/10.60988/p.v37i2S.230Keywords:
esculetin; isoproterenol; myocardial infarction; intestinal dysbiosis; ratAbstract
Myocardial infarction (MI), a prevalent form of cardiovascular disease, has been associated with alterations in gut microbiota composition. Esculetin, a coumarin derivative, possesses multiple therapeutic properties. This study aimed at investigating the potential protective role of esculetin against isoproterenol (ISO)-induced myocardial toxicity in male rats, with a particular focus on intestinal dysbiosis and histopathological changes. The experimental protocol spanned 21 days, during which rats were randomly assigned to five groups (n=6 per group): (i) group 1 (normal control) received normal saline, (ii) group 2 (positive control) was administered ISO at 100 mg/kg, subcutaneously, every 24 h for two consecutive days, and (iii) groups 3, 4, and 5 were similarly administered ISO (100 mg/kg, subcutaneously, every 24 h for two days), followed from day 3 by oral esculetin at doses of 20, 40, and 60 mg/kg once daily, respectively. ISO administration significantly elevated serum creatine kinase-MB (CK-MB) levels, indicating myocardial injury. Esculetin treatment markedly reduced CK-MB levels in a dose-dependent manner. ISO also significantly decreased sodium–potassium adenosine triphosphatase (Na+,K+-ATPase) activity (a key marker of cellular membrane integrity and ion transport) while esculetin administration restored its activity. Histopathological examination of the small intestine in ISO-treated rats revealed severe enteritis characterized by villous damage, epithelial sloughing, vascular congestion, and pronounced leukocyte infiltration. Esculetin treatment ameliorated these changes, with the highest dose (60 mg/kg) yielding the most notable improvements, including restoration of normal villous architecture, enterocyte integrity, and intestinal gland morphology. These findings suggest that esculetin exerts protective effects against ISO-induced MI by mitigating cardiac toxicity, reversing intestinal dysbiosis, and improving histopathological outcomes.
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