Curcumin Downregulates Phosphate Carrier and Protects against Doxorubicin Induced Cardiomyocyte Apoptosis

Abstract

Aim. To explore the effects of curcumin on phosphate carrier (PiC) and its role in protection against doxorubicin induced myocyte toxicity. Methods. Using H9c2 cell line, the cardiotoxic effect of doxorubicin and its mitigation by curcumin were studied. H9c2 cells were cultured with doxorubicin and/or curcumin at various concentrations. Analysis for apoptosis of H9c2 was done using flow cytometry. Confocal laser scanning microscopy was used to record the fluorescence intensity ratios and to determine the mitochondrial permeability transition pore (MPTP) opening state. Oxidative stress was measured using glutathione level, superoxide dismutase activities, and malondialdehyde content. The effect of doxorubicin and curcumin on PiC gene expression was measured by real-time PCR. Results. Curcumin decreased mRNA of PiC and was partly protective against oxidative stress, loss of mitochondrial transmembrane potential, and apoptosis induced by doxorubicin. Interestingly, the effect was not clearly dose dependent and the concentration of 12 mg/L was more efficient than 15 and 10 mg/L. Conclusion. Curcumin downregulates PiC and partly protects against doxorubicin induced oxidative stress and myocyte apoptosis.

Ursolic acid prevents doxorubicin‐induced cardiac toxicity in mice through eNOS activation and inhibition of eNOS uncoupling

“…Multiple reports have demonstrated that doxorubicin-induced cardiac toxicity is decreased by anti-apoptotic methods in various animal models. [26][27][28] It is known that ursolic acid protects the heart from ischaemic reperfusion injury or infarction by anti-apoptotic activities. [29][30][31] Therefore, via anti-apoptosis, ursolic acid may decrease the side effects of doxorubicin on the heart.…”

Oral administration of Ginsenoside Rg1 prevents cardiac toxicity induced by doxorubicin in mice through anti-apoptosis

“…Thus, the strategy against the mitochondrial pathway of apoptosis is reasonable in preventing the cardiac toxicity caused by doxorubicin. Reportedly, the cardiac toxicity caused by doxorubicin is decreased in various animal models by the antiapoptotic methods [ 26 – 28 ]. Several studies showed that Rg1 protects the heart from ischemic reperfusion injury or heart infarction by the effect of anti-apoptosis [ 17 – 19 ].…”

Mitochondria-Targeting Small Molecules Effectively Prevent Cardiotoxicity Induced by Doxorubicin

“…Several studies have shown that curcumin could protect against Dox-induced cardiotoxicity. The key mechanisms postulated for the cardioprotective activity of curcumin include induction of apoptosis, JNK activation, abrogation of inflammation, and excessive opening of mitochondrial permeability transition pores [ 35 , 36 , 37 , 38 , 39 , 40 ]. Therefore, pre-treatment with curcumin could be considered in cancer chemotherapeutic applications.…”