H2O2-Responsive Antioxidant Nanoparticle Attenuates Whole Body Ischemia/Reperfusion-Induced Multi-Organ Damages

Abstract

Mortality and morbidity after cardiac arrest remain high due to ischemia/reperfusion (I/R) injury causing multi-organ damages, even after successful return of spontaneous circulation. We previously generated H2O2-activatable antioxidant nanoparticles formulated with copolyoxalate containing vanillyl alcohol (PVAX) to prevent I/R injury. In this study, we examined whether PVAX could effectively reduce organ damages in a rat model of whole-body ischemia/reperfusion injury (WBIR). To induce a cardiac arrest, 70µl/100 g body weight of 1 mmol/l potassium chloride was administered via the jugular venous catheter. The animals in both the vehicle and PVAX-treated groups had similar baseline blood pressure. After 5.5 minutes of cardiac arrest, animals were resuscitated via intravenous epinephrine followed by chest compressions. PVAX or vehicle was injected after the spontaneous recovery of blood pressure was noted, followed by the same dose of second injection 10 minutes later. After 24 hours, multiple organs were harvested for pathological, biochemical, molecular analyses. No significant difference on the restoration of spontaneous circulation was observed between vehicle and PVAX groups. Analysis of organs harvested 24 hours post procedure showed that whole body I/R significantly increased reactive oxygen species (ROS) generation, inflammatory markers, and apoptosis in multiple organs (heart, brain, and kidney). PVAX treatment effectively blocked ROS generation, reduced the elevation of pro-inflammatory cytokines, and decreased apoptosis in these organs. Taken together, our results suggest that PVAX has potent protective effect against WBIR induced multi-organ injury, possibly by blocking ROS-mediated cell damage.

Naringenin attenuates cerebral ischemia/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/FOXO1 signaling pathway in vitro

“…For decades, numerous clinical trials have evaluated that oxidative stress plays crucial roles in the occurrence and development of cerebral I/R injury and the impairment of antioxidant defense system including SOD, GSH-Px, and CAT activities endogenously formed by I/R are most applicable 42 - 44 . Naringenin is neuroprotective against a variety of neurological diseases associated with antioxidant mechanisms and inhibition of lipid peroxidation 45 - 47 .…”

Redox Responsive Copolyoxalate Smart Polymers for Inflammation and Other Aging-Associated Diseases

“…There was no alteration of intracellular NADPH oxidase 2 activity ( Figure S3 ) [ 34 ]. CPOx nanoparticles treatment systemically showed that there were no adverse reactions induced by the nano formulations in the histology of TUNNEL ( Figure S4 ) [ 35 ]. Biomedical application of the Pox and various CPOx are summarized in Table S1 .…”