title: Polydatin, a natural polyphenol, protects arterial smooth muscle cells against mitochondrial dysfunction and lysosomal destabilization following hemorrhagic shock.
abstract: 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-Co(2+) technique revealed opening of ASMC mitochondrial permeability transition pores (mPTP) after shock with resulting mitochondrial swelling, decreased mitochondrial membrane potential (ΔΨm), 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.
authors.affiliation: Guangdong Key Laboratory of Shock and Microcirculation Research, Dept. of Pathophysiology, Southern Medical Univ., Guangzhou, P. R. China.
authors.forename: Xingmin
authors.initials: X
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Song
authors.forename: Hui Ning
authors.initials: HN
authors.lastname: Bian
authors.forename: Ulf T
authors.initials: UT
authors.lastname: Brunk
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Ke-Seng
authors.initials: KS
authors.lastname: Zhao
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D019610:Cytoprotection; D005960:Glucosides / Q000008:administration & dosage*; D054086:KATP Channels / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008931:Mitochondria, Muscle / Q000187:drug effects*; D028361:Mitochondrial Diseases / Q000209:etiology / Q000517:prevention & control*; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D000077185:Resveratrol; D012771:Shock, Hemorrhagic / Q000150:complications*; D013267:Stilbenes / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005960:Glucosides; D054086:KATP Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013267:Stilbenes; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D000077185:Resveratrol; D009638:Norepinephrine; C058229:polydatin