Curcumin Attenuates Ferroptosis-Induced Myocardial Injury in Diabetic Cardiomyopathy through the Nrf2 Pathway

Abstract

Diabetes causes lipid peroxide to accumulate within cardiomyocytes. Furthermore, lipid peroxide buildup is a risk factor for ferroptosis. This study is aimed at examining whether curcumin can ameliorate ferroptosis in the treatment of diabetic cardiomyopathy. Hematoxylin and eosin and Masson sections were used to examine the morphology, arrangement, and degree of fibrosis of the myocardium of diabetic rabbit models. The expression levels of nuclear Nrf2, Gpx4, Cox1, and Acsl4 in diabetic animal and cell models were quantitatively analyzed using immunofluorescence and western blotting. Nrf2-overexpression lentivirus vectors were transfected into cardiomyocytes, and the protective effects of curcumin and Nrf2 on cardiomyocytes under high glucose stimulation were assessed using terminal deoxynucleotidyl transferase dUTP nick-end labelling and reactive oxygen species probes. Diabetes was found to disorder myocardial cell arrangement and significantly increase the degree of myocardial fibrosis and collagen expression in myocardial cells. Curcumin treatment can increase nuclear transfer of Nrf2 and the expression of Gpx4 and HO-1, reduce glucose induced myocardial cell damage, and reverse myocardial cell damage caused by the ferroptosis inducer erastin. This study confirmed that curcumin can promote the nuclear translocation of Nrf2, increase the expression of oxidative scavenging factors, such as HO-1, reduce excessive Gpx4 loss, and inhibit glucose-induced ferroptosis in cardiomyocytes. This highlights a potentially new therapeutic route for investigation for the treatment diabetic cardiomyopathy.

Ferroptosis: A potential target for the intervention of intervertebral disc degeneration

“…Furthermore, folic acid, a coenzyme in the methionine cycle, has been regarded as another ferroptosisrelated therapeutic drug for IVDD caused by Hcy through the downregulation of GPX4 methylation and oxidative stress, thereby rescuing ferroptosis-induced NPC degeneration (44). In addition, other antioxidants and drugs, such as vitamin E, vitamin K, and curcumin, have exerted protective effects on ferroptosis (149)(150)(151)(152). Moreover, the essential regulators of ferroptosis, such as ferritin, FPN1, NRF2, GPX4, GSH, HO-1, and TFRC, can be selected as the regulation targets for the treatment of IVDD.…”

New Insights into the Role of Ferroptosis in Cardiovascular Diseases

“…Interestingly, Nrf2 activated by sulforaphane was shown to suppress cardiac cell ferroptosis in both AGE-treated ECTs and the hearts of diabetic cardiomyopathy mice by upregulating ferritin and SLC7A11 [ 150 ]. These protective effects on ferroptosis have been confirmed using other Nrf2 activators such as curcumin [ 163 ] and 6-gingerol [ 164 ] in animal models and in cardiomyocytes. Nevertheless, as emphasized above, it is known that Nrf2 increases HO-1 which degrades heme and makes available free iron that additionally favors lipid peroxidation [ 10 ].…”

Ferroptosis, necroptosis and cuproptosis: Novel forms of regulated cell death in diabetic cardiomyopathy

“…Increasing evidence shows that ferroptosis is involved in the onset and progression of DCM, and ferroptosis also affects the pathological consequences of cardiac function (79)(80)(81)(82). These findings identify ferroptosis as a promising cellular target for correcting heart function in patients with DCM and possibly also for delaying the degenerative progression of DCM.…”