Methylene blue ameliorates mitochondrial function of rat kidney during experimental acute pancreatitis

Abstract

Introduction: Systemic inflammatory response syndrome in severe acute pancreatitis (AP) leads to multiple organ dysfunction that is the main cause of death. Renal failure is of utmost importance and has a large impact on mortality rate. Our previous data revealed that mitochondrial energy metabolism in kidney is disturbed during experimental AP and may play an important role in the development and progression of renal failure. The effects of methylene blue on mitochondrial respiratory functions of rat kidney during severe experimental AP were investigated in this study. Aims&methods: AP was induced in 10 male Wistar rats by intraductal application of sodium taurocholate (5%, 1,75 mL/kg). Animals were divided into two groups: experimental group – methylene blue (5mg/kg) was injected intravenously 10 min prior to AP induction; control group – saline solution intravenously 10 min prior to AP induction. Animals were sacrificed after 24 hours from the induction of AP. Kidney were removed for mitochondrial assay by oxygraphic and spectrophotometric methods. Results: We found that AP-induced kidney mitochondrial dysfunction was restored with methylene blue intravenous injection. Thus, our data indicate clear increase in mitochondrial State 3 respiration rate (by 62%, p50.05) and in respiratory control index (RCI, by 30%) with mitochondrial complex I linked substrate glutamate/malate in the group after methylene blue treatment as compared to untreated group. The Complex I activity was increased by two-fold (p50.05) after methylene blue treatment. Methylene blue slightly increased RCI with Complex II dependent substrate succinate (by 16%, p50.05), though had no effect on State 3 respiration rate with this substrate. Conclusion: Our data show that disturbances of mitochondrial energy metabolism during AP in kidney mitochondria could be ameliorated with methylene blue intravenous injection. This may be a promising agent fo