Atorvastatin alleviates experimental diabetic cardiomyopathy by suppressing apoptosis and oxidative stress

Abstract

Diabetic hazard on the myocardium is a complication of diabetes that intensifies its morbidity and increases its mortality. Therefore, alleviation of diabetic cardiomyopathy (DCM) by a reliable drug remains a matter of interest in experimental research. The aim of this study was to explore the structural alterations in the myocardium induced by atorvastatin (ATOR) in DCM, induced by streptozotocin (STZ), along with the associated changes occurring in apoptosis and oxidative stress markers. Thirty-two rats were divided into four groups; group A (control), group B (non-diabetic, received ATOR, orally, 50 mg/kg daily), group C (DCM, received STZ 70 mg/kg, single i.p. injection) and group D (DCM + ATOR). After 6 weeks, left ventricle (LV) specimens were prepared for histological and immunohistochemical study by hematoxlyin and eosin, Masson`s trichrome, anti-cleaved caspase-3 stains as well as for assays of oxidative stress markers. All data were measured morphometrically and statistically analyzed. The DCM group showed disorganization of the cardiomyocytes, interstitial edema, numerous fibroblasts, significant increases in the collagen volume fraction (p < 0.001), cleaved caspase-3 expression % area (p < 0.001) and, malondialdehyde in blood (p < 0.001), in LV (p < 0.05) compared with DCM + ATOR group. The latter has LV wall thickness, relative heart weight and antioxidant activities nearly similar to the control, independent from ATOR lipid-lowering effect. Therefore, ATOR can preserve myocardial structure in DCM nearly similar to normal. This may be achieved by suppressing apoptosis that parallels the correction of the antioxidant markers, which can be considered as non-lipid lowering benefit of statins.

Atorvastatin Alleviates Experimental Diabetic Cardiomyopathy by Regulating the GSK-3β-PP2Ac-NF-κB Signaling Axis

“…In recent studies, the drug alleviated progression of experimental DCM, possibly by a protective effect against apoptosis, independent of its LDL-cholesterol-lowering properties [14]. We demonstrated in this study that the anti-apoptotic and cardioprotective effects of ATOR may be explained by inhibition of sustained activation of NF-κB signaling.…”

“…Mice were sacrificed and their hearts harvested and fixed in 4% paraformaldehyde, embedded in paraffin and sectioned (3–4 μm thickness) [14]. After dehydration, sections were stained with hematoxylin-eosin (H-E) and prepared for Masson's trichrome staining.…”

“…A recent study reported that ATOR alleviated progression of experimental DCM, possibly because of its protective effects against apoptosis, independent of LDL-cholesterol-lowering [14]. Furthermore, Jin et al [15] found that ATOR enhanced neurite outgrowth in cultured cortical neurons by inactivating GSK-3β.…”

The effect of Astragalus polysaccharides on attenuation of diabetic cardiomyopathy through inhibiting the extrinsic and intrinsic apoptotic pathways in high glucose -stimulated H9C2 cells

“…The extent of cardiomyocyte death parallels the severity of the diabetic cardiomyopathy and its stage of evolution [7]. Attenuation of cardiomyocyte apoptosis has been shown to prevent diabetic cardiomyopathy [8, 9]. The mechanisms of apoptosis involved in diabetic cardiomyopathy are not clear.…”

Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia

“…33 AbdelHamid et al also suggested that atorvastatin could preserve myocardial structure in diabetic cardiomyopathy by suppressing cardiomyocyte apoptosis and oxidative stress. 34 These results indicate that atorvastatin has heartprotective effects from oxidative stress. The findings of our study indicate that TNF-a induced by hypoxia is inhibited by atorvastatin.…”