Abstract:

Objective  To explore the effect of pre-treatment with lidocaine(LIDO) on alleviating doxorubicin(DOX)-induced myocardial injury and the underlying mechanism.

Methods  A total of 30 mice obtained from Institute of Cancer Research(ICR) were selected and randomly assigned into control group(a single intraperitoneal injection of 1 mL/100 g normal saline, n=10), DOX group(a single intraperitoneal injection of 10 mg/kg DOX, n=10) and DOX+LIDO group(tail vein injection of 6 mg/kg LIDO, followed by a single intraperitoneal injection of 10 mg/kg DOX 30 min later, n=10). Body weight, survival rate and electrocardiogram(ECG) findings of the mice among three groups were observed. In addition, serum levels of cardiac troponin-T(cTn-T), interleukin-1β(IL-1β), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α), as well as relative levels of phosphorylated adenosine phosphate activated protein kinase（ p-AMPK） and phosphorylated connexin 43（p-Cx43） in myocardial tissues of mice were measured and compared.

Results  Compared with those in control group, mice in DOX group presented significantly reduced body weight at 2-7 d, increased 7-day mortality, and lowered heart rate. In addition, significantly higher serum levels of cTn-T, IL-1β, IL-6 and TNF-α, as well as downregulated p-AMPK and upregulated p-Cx43 in myocardial tissues were detected in DOX group, as compared with those of control group. Notably, compared with those in DOX group, LIDO pre-treatment significantly reversed DOX-induced reduction of body weight, increase in 7-day mortality, and decline of heart rate, which also reversed increased serum levels of cTn-T, IL-1β, IL-6 and TNF-α, downregulated p-AMPK and upregulated p-Cx43 in myocardial tissues.

Conclusion  LIDO pre-treatment effectively alleviates DOX-induced myocardial injury of mice possibly by activating AMPK and inhibiting p-Cx43.

Key words: myocardial disease, doxorubicin, lidocaine