Beta-glucan protects against isoproterenol-induced cardiac remodeling by regulating the ACE-AT ₁R axis and attenuates cardiac inflammation and apoptosis

Abstract

Objective: To investigate the cardioprotective effect of beta-glucan against isoproterenol-induced cardiotoxicity in rats, and elucidate the underlying mechanism. Methods: Rats were orally pretreated with beta-glucan (40 mg/kg body weight) for 30 d, and isoproterenol (20 mg/100 g body weight) was administered on days 31 and 32. The effects of beta-glucan on markers of cardiac injury, hemodynamic changes, production of proinflammatory cytokines, and the corresponding mRNA expressions were evaluated. In addition, histological analysis was performed. Results: Pretreatment with beta-glucan prevented isoproterenol-induced cardiac injury by preserving the structural and functional integrity of the plasma membrane and attenuating the production of proinflammatory cytokines (NF-κB, TNF-α, IL-6, IL-1β, and IFN-γ) in the heart. Moreover, beta-glucan significantly downregulated the mRNA expression of ACE, AT₁R, TNF-α, IL-6, NF-κB, caspase-3, TLR-4, and Bax, and upregulated Bcl-2 in the heart. At the same time, pretreatment with beta-glucan alleviated myocardial damage as reflected in a reduction in myonecrosis, edema, and erythrocyte extravasation with almost imperceptible inflammation. Conclusions: Beta-glucan can protect against isoproterenol-induced cardiotoxicity by attenuating cardiac inflammation and apoptosis and regulating the ACE-AT₁R axis, thereby preventing cardiac remodeling.

Keywords

Βeta-glucan / Isoproterenol / Cardiac inflammation / Cardiac apoptosis / Cardiovascular diseases / Heart failure / Myocardial infarction

Acknowledgments

Authors would like to express their sincere thanks to the management of Nandha College of Pharmacy, Erode, and Tamilnadu for providing the Animal House Facility for this study.

Conflict of interest statement

The authors declare no competing interests.

Funding

The authors received no extramural funding for the study.

Authors’ contributions

AR and VVSU wrote the manuscript; AR, VMN, JG, BRA, SK, and VVSU performed experiments and collected the data; AR, VMN, and SS analyzed the data; AR, VVSU, and SS designed the study; VMN, JG, BRA, SK and SS reviewed the manuscript. All authors read and approved the final manuscript.

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