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Artemisinin attenuates cardiac depression by down-regulating the NF-κB/MMP2 pathway during endotoxemia

 

 
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doi: 10.18081/pcij/2378-5225/012-12/20-34    
Pathophysiology of Cell Injury Journal  Volume 1, Issue 1, pages 20-34 December 2012

Gu Y, Wang X, Wang X, Yuan M, Wu G, Hu J, Tang Y, Huang C.

Abstract

Myocardial endotoxmia leads to progressive left ventricular (LV) dilatation. The NF-κB signaling pathway plays an important role in ventricular injury after endotoxmia. Recent studies have indicated that the anti-malarial agent artemisinin can inhibit NF-κB activation, which may attenuate post-myocardial injury. In this study, we investigated the effect of artemisinin on myocardial endotoxemia using a rat model of sepsis. Adult male Sprague Dawley rats were divided into a sham group (n = 10) and sepsis groups that were treated either with oral gavage of artemisinin (75 mg/kg/day, n = 20) or vehicle (0.5% carboxymethyl cellulose, n = 20) three times a day for 4 days. Each treatment was started at 24 hours after sepsis. Four days after sepsis, the artemisinin-treated group showed a significantly improved survival rate compared with that of the vehicle-treated group (65% vs. 40%, P < 0.05). Echocardiography showed significant improvements in cardiac function and left ventricular dimensions in the artemisinin-treated group. Moreover, the degree of myocardial fibrosis and elevated levels of fibrosis-related factors [transforming growth factor-β1, collagen type I, and MMP-9] were remarkably ameliorated by artemisinin (all P < 0.05). Importantly, artemisinin inhibited the NF-κB pathway by blocking IKBα phosphorylation. BUT without any role of MMP-2 pathway [similar to other]. In conclusion, artemisinin may attenuate post-myocardial sepsis by down-regulating the NF-κB pathway only.

Keywords: Artemisinin; NF-κB; Sepsis; MMP-9

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