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Curcumin is a pigment containing diketone and has extensive biological activity. Previous studies have showed that curcumin could effectively reduce the risk of cardiovascular disease. However, the mechanisms of curcumin protective effect on the heart are still unclear. The purpose of this research is to clarify relation between the concentrations of curcumin and the degree of DNA damage, and analyze the molecular mechanism of curcumin effect.
8-week mice were subcutaneously injected with 1, 10, 20 and 40mg/kg/day curcumin dissolving in DMSO or normal saline for 3 days, and then were injected with 30mg/kg/day isoproterenol (Iso). 7 days later, mice were detected by Vevo 770 ultrasonic diagnostic apparatus, respectively. Similarly, cardiomyocytes isolated from neonatal rats were pretreated by PBS or 1, 10 and 20μM curcumin, and then were induced by Iso. The protein of phosphorylated ataxia telangiectasia mutated (p-ATM), phospho-Rad3-related protein (p-ATR), γ-H2AX, breast cancer 1 (BRCA1) and C-terminal Src homologous kinase (Chk) were measured by western blot analysis. The mRNA level and the protein level of P21 were detected by real-time PCR and western blot analysis.
Comparing with normal saline/Iso group, EF value and FS value of mice were significantly decreased in 20 and 40mg/kg/day curcumin/Iso group. The expression levels of DNA damage related proteins were obviously decreased with the pre-treatment of curcumin. EF value, FS value and DNA damage related protein expression were dependent on curcumin dose reduction.
These findings suggest curcumin could improve cardiac function via repairing DNA damage caused by Iso in cardiac muscle cells.