Polydatin, a natural polyphenol, protects arterial smooth muscle cells against mitochondrial dysfunction and lysosomal destabilization following hemorrhagic shock
2012 (English)In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 302, no 7, R805-R814 p.Article in journal (Refereed) Published
The main objective of this study was to investigate the activity of polydatin on mitochondrial dysfunction and lysosomal stability of arteriolar smooth muscle cells (ASMCs) in severe shock. The experimental animals (rats) were divided into five groups: control, hemorrhagic shock, shock + CsA, shock + Res, and shock + PD (exposed to cyclosporin A, resveratrol, or polydatin following induction of hemorrhagic shock, respectively). The calcein-Co2+ technique revealed opening of ASMC mitochondrial permeability transition pores (mPTP) after shock with resulting mitochondrial swelling, decreased mitochondrial membrane potential (Delta Psi m), and reduced intracellular ATP levels. These alterations were all inhibited by exposure to PD, which was significantly more effective than CsA and Res. PD also preserved lysosomal stability, suppressed activation of K-ATP channels, ASMC hyperpolarization, and reduced vasoresponsiveness to norepinephrine that normally follows severe shock. The results demonstrate that exposure to PD after initiation of severe shock effectively preserves ASMC mitochondrial integrity and has a significant therapeutic effect in severe shock. The effects may partially result from lysosomal stabilization against shock-induced oxidative stress and depressed relocation of hydrolytic enzymes and redox-active lysosomal iron that, in turn, may induce mPTP opening.
Place, publisher, year, edition, pages
American Physiological Society , 2012. Vol. 302, no 7, R805-R814 p.
hemorrhagic shock, hypotension, polydatin, lysosomes
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-76951DOI: 10.1152/ajpregu.00350.2011ISI: 000302348600002OAI: oai:DiVA.org:liu-76951DiVA: diva2:524361
Funding Agencies|National Natural Science Foundation of China|3067217930971202|Program for Changjiang Scholars||Innovative Research Team in University, China|IRTO731|2012-05-022012-04-272012-05-02