Abstract
Myocardial fibrosis is one of the major complications of long-term diabetes. Hyperglycemia induced cardiomyocyte atrophy is a frequent pathophysiological indicator of diabetic heart. The objective of this study was to investigate the cardioprotective effect of glycyrrhizin (GLC) on myocardial damage in diabetic rats and assess the anti-inflammatory and anti-fibrotic effect of GLC. Our study demonstrates that hyperglycemia can elevate cardiac atrophy in diabetic animals. Type 2 diabetic fatty and the lean control rats were evaluated for cardiac damage and inflammation at 8–12 weeks after the development of diabetes. Western blot and immunohistochemical studies revealed that gap junction protein connexin-43 (CX43), cardiac injury marker troponin I, cardiac muscle specific voltage gated sodium channel NaV1.5 were significantly altered in the diabetic heart. Furthermore, oxidative stress mediator receptor for advanced glycation end-products (RAGE), as well as inflammatory mediator phospho-p38 MAPK and chemokine receptor CXCR4 were increased in the diabetic heart whereas the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), the antioxidant proteins that protect against oxidative damage was reduced. We also observed an increase in the expression of the pleiotropic cytokine, transforming growth factor beta (TGF-β) in the diabetic heart. GLC treatment exhibited a decrease in the expression of phospho-p38 MAPK, RAGE, NaV1.5 and TGF-β and it also altered the expression of CX43, CXCR4, Nrf2 and troponin I. These observations suggest that GLC possesses cardioprotective effects in diabetic cardiac atrophy and that these effects could be mediated through activation of Nrf2 and inhibition of CXCR4/SDF1 as well as TGF-β/p38MAPK signaling pathway.
Highlights
IntroductionProlonged exposure to high glucose due to diabetes can affect macro and microvascular systems causing cardiovascular complications [3,4]
Our study demonstrates a significant increase in NaV 1.5 expression in the ventricular diabetic heart tissue of the ZDF rats, suggesting that there could be alteration in glycosylation or changes in protein turnover which may contribute to the increased expression of NaV 1.5 in diabetic animals compared to lean controls
Hyperglycemic condition in diabetes can elevate oxidative stress and inflammation that may result in cardiac remodeling and may lead to hypertrophy of the myocardium
Summary
Prolonged exposure to high glucose due to diabetes can affect macro and microvascular systems causing cardiovascular complications [3,4]. 463 million people are living with diabetes worldwide and it is projected to rise to 700 million by the year 2045. 11.3% deaths worldwide are attributed to diabetes and its complications [5] and cardiovascular diseases are one of the major complications, as well as a major cause of mortality in diabetic patients [6]. The cells that are responsible for generating contractile forces in the heart could lead to the development of diabetic cardiomyopathy [7]. A number of mechanisms prompting cardiomyocyte death have been projected, including inflammation, oxidative stress, glucose mediated toxicity and Biomolecules 2021, 11, 569.
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