Résumé
Type 2 diabetes is associated with a higher cardiac vulnerability to ischemia-reperfusion (IR), mainly explained by higher oxidative stress during early reperfusion. We previously reported that anamphiphilic nitrone spin trap called LPBNAH, was able to protect the heart against IR. However, whether this molecule is able to protect the heart of diabetic mice has never been challenged. The aim of this work was then to evaluate whether the heart of obese diabetic mice treated with LPBNAH antioxidant could be protected during IR. C57Bl6 mice were fed with high fat and high sucrose diet (HFS) for 12 weeks and exhibited higher body weight and adipose tissue associated with higher HOMA-IR. After 12 weeks of HFS diet mice were treated or not with LPBNAH for five consecutive days at the dose of 2.5 mg/kg or 0.5 mg/kg (i.p.). Finally hearts were mounted on a Langendorff perfusion apparatus and a protocol of IR was performed. The heart of obese diabetic mice was more vulnerable to IR. This was characterized by lower recovery of cardiac function during post-ischemic reperfusion and higher infarct size. In addition, during reperfusion, higher ROS production and lipid peroxidation were reported in HFS heart compared to Ctrl ones, highlighting then the key role of oxidative stress. Obese diabetic mice treated with LPBNAH (0.5 mg/kg) were less sensitive to IR than their non-treated counterparts. Indeed left ventricular developed pressure was significantly higher and infarct size normalized at level seen in non-obese diabetic mice. Interestingly, we compared the effect to those obtained with exercise training, a highly recognized strategy to protect the heart. We reported that protection afforded by LPBNAH treatment was comparable to those obtained with 4 weeks of exercise training. In conclusion, a five days treatment with the amphiphilic nitrone antioxidant LPBNAH protects the heart of obese diabetic mice against IR injuries in a similar manner that 4 weeks of exercise training.
The author hereby declares no conflict of interest