Methylene Blue Protects Liver Oxidative Capacity after Gut Ischaemia–Reperfusion in the Rat

Abstract

ObjectivesMesenteric 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. DesignControlled animal study. Materials and methodsRats 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. ResultsGut 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 O2 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 (r2 = 0.45). MB restored liver mitochondrial function. ConclusionsMB protected against gut IR-induced liver mitochondria dysfunction.