While survival rates have markedly improved following cardiac ischemia-reperfusion (IR) injury, the resulting heart damage remains an important issue. Preserving mitochondrial quality and limiting NLRP3 inflammasome activation is an approach to limit IR injury, in which the mitochondrial deacetylase sirtuin 3 (SIRT3) has a role. Recent data demonstrate cytochrome P450 (CYP450)-derived epoxy metabolites, epoxydocosapentaenoic acids (EDPs), of docosahexaenoic acid (DHA), attenuate cardiac IR injury. EDPs undergo rapid removal and inactivation by enzymatic and non-enzymatic processes. The current study hypothesizes that the cardioprotective effects of the synthetic EDP surrogates AS-27, SA-26 and AA-4 against IR injury involve activation of SIRT3. Isolated hearts from wild type (WT) mice were perfused in the Langendorff mode with vehicle, AS-27, SA-26 or AA-4. Improved postischemic functional recovery, maintained cardiac ATP levels, reduced oxidative stress and attenuation of NLRP3 activation were observed in hearts perfused with the analogue SA-26. Assessment of cardiac mitochondria demonstrated SA-26 preserved SIRT3 activity and reduced acetylation of manganese superoxide dismutase (MnSOD) suggesting enhanced antioxidant capacity. Together, these data demonstrate that the cardioprotective effects of the EDP analogue SA-26 against IR injury involve preservation of mitochondrial SIRT3 activity, which attenuates a detrimental innate NLRP3 inflammasome response.
Extensive use of zinc oxide and accelerators such as diphenyl guanidine (DPG) in the vulcanization of rubber composites entail potential environmental risks. These are pervasive contaminants of roadway runoff originating from tire wear particles (TWPs). Herein, the effect of phosphonium ionic liquids (PILs) in styrene-butadiene rubber compounds was demonstrated with reduced ZnO loading and no DPG to minimize the environmental footprint of the vulcanization process. The structure and chemistry of PILs were found to be the influencing parameters impelling the cross-linking kinetics, enabling shorter induction times. The generation of active Zn 2 + sites by PILs was examined through FTIR spectroscopy, calorimetry, and molecular dynamics simulations. From a tire application perspective, the PILs not only enhanced the cure kinetics but also improved the dynamic-mechanical behavior of the rubber composites. Consequently, the harm caused by TWPs to the atmosphere, fuel intake, and CO 2 emissions was minimal, thereby confirming the potential use of PILs in the tire industry.
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