title: Glycine preconditioning to ameliorate pulmonary ischemia reperfusion injury in rats.
abstract: This study examines the impact of glycine (Gly) preconditioning on ischemia reperfusion (IR)-induced pulmonary mitochondrial injury to research the previously, in pig lungs, demonstrated Gly-dependent amelioration of pulmonary IR injury. IR injury was induced in rat lungs by 30 min pulmonary hilum clamping followed by 60 min reperfusion time. Rats were subjected to controls, shams and two study groups (IR30/60, Gly-IR30/60) receiving 37.5 mg Gly i.v. or not before IR induction. The wet/dry-weight ratio, mitochondria viability (MV), membrane integrity (MI), respiratory chain complex (RCC) activities, mitochondrial membrane potential (ΔΨm) and cytochrome C (Cyt C) content were analysed. In IR30/60, RCC and MV were impaired; Cyt C loss and MI combined with matrix metalloproteinase-9 (MMP-9) activation and ΔΨm alteration were observed when compared with controls. In Gly-IR30/60, complex II function and mitochondrial viability were protected during IR, and MMP-9 activation combined with tissue-water content accumulation and ΔΨm alteration were ameliorated. Cyt C loss, mitochondrial membranes damage, tissue GSH oxidation or neutrophil sequestration was not extenuated in Gly-IR30/60. Gly ameliorates IR-associated mitochondrial dysfunction and decay of viability and normalizes ΔΨm but does not protect from Cyt C liberation and mitochondrial membrane damage. Our data suggest that the previously described effect of Gly preconditioning results at least partially from mitochondrial protection. A dose-finding study is necessary to improve results of Gly preconditioning.
authors.affiliation: Department of Cardiothoracic and Thoracic Vascular Surgery, University Hospital Würzburg, Würzburg, Germany. sommer_s1@klinik.uni-wuerzburg.de
authors.forename: Sebastian-Patrick
authors.initials: SP
authors.lastname: Sommer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sommer
authors.forename: Bhanu
authors.initials: B
authors.lastname: Sinha
authors.forename: Rainer G
authors.initials: RG
authors.lastname: Leyh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010084:Oxidation-Reduction; D020011:Protective Agents / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
chemical_list: D045222:Electron Transport Chain Complex Proteins; D020011:Protective Agents; D045304:Cytochromes c; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D005978:Glutathione; D005998:Glycine