title: Methylene blue protects liver oxidative capacity after gut ischaemia-reperfusion in the rat.
abstract: OBJECTIVE
  Mesenteric ischaemia/reperfusion (IR) may lead to liver mitochondrial dysfunction and multiple organ failure. We determined whether gut IR induces early impairment of liver mitochondrial oxidative activity and whether methylene blue (MB) might afford protection.
  
  
  METHODS
  Controlled animal study.
  
  
  METHODS
  Rats were randomised into three groups: controls (n = 18), gut IR group (mesenteric ischaemia (60 min)/reperfusion (60 min)) (n = 18) and gut IR + MB group (15 mg kg(-1) MB intra-peritoneally) (n = 16). Study parameters were: serum liver function markers, blood lactate, standard histology and DNA fragmentation (apoptosis) on intestinal and liver tissue, maximal oxidative capacity of liver mitochondria (state 3) and activity of complexes II, III and IV of the respiratory chain measured using a Clark oxygen electrode.
  
  
  RESULTS
  Gut IR increased lactate deshydrogenase (+982%), aspartate and alanine aminotransferases (+43% and +74%, respectively) and lactate levels (+271%). It induced segmental loss of intestinal villi and cryptic apoptosis. It reduced liver state 3 respiration by 30% from 50.1 ± 3 to 35.2 ± 3.5 μM O(2) min(-1) g(-1) (P < 0.01) and the activity of complexes II, III and IV of the mitochondrial respiratory chain. Early impairment of liver mitochondrial respiration was related to blood lactate levels (r(2) = 0.45). MB restored liver mitochondrial function.
  
  
  CONCLUSIONS
  MB protected against gut IR-induced liver mitochondria dysfunction.
authors.affiliation: Pôle Anesthésie, Réanimation Chirurgicale, SAMU, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Olivier.collange@chru-strasbourg.fr
authors.forename: O
authors.initials: O
authors.lastname: Collange
authors.forename: A-L
authors.initials: AL
authors.lastname: Charles
authors.forename: J
authors.initials: J
authors.lastname: Bouitbir
authors.forename: M-P
authors.initials: MP
authors.lastname: Chenard
authors.forename: J
authors.initials: J
authors.lastname: Zoll
authors.forename: P
authors.initials: P
authors.lastname: Diemunsch
authors.forename: F
authors.initials: F
authors.lastname: Thaveau
authors.forename: N
authors.initials: N
authors.lastname: Chakfé
authors.forename: F
authors.initials: F
authors.lastname: Piquard
authors.forename: B
authors.initials: B
authors.lastname: Geny
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D019610:Cytoprotection; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D008751:Methylene Blue / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D020011:Protective Agents; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D014450:Electron Transport Complex III; D008751:Methylene Blue