Effect of Hepatic Preconditioning with the Use of Methylene Blue on the Liver of Wistar Rats Submitted to Ischemia and Reperfusion

Background

The liver may be injured in situations where it is submitted to ischemia, such as partial hepatectomy and liver transplantation. In all cases, ischemia is followed by reperfusion and, although it is essential for the reestablishment of tissue function, reperfusion may cause greater damage than ischemia, an injury characterized as ischemia-reperfusion (I/R) damage. The aim of this work was to analyze the effect of ischemic preconditioning with the use of methylene blue (MB; 15 mg/kg) 5 or 15 minutes before I/R (IRMB5′ and IRMB15′, respectively) on the hepatic injury occurring after I/R.

Methods

Twenty-eight male Wistar rats were used, and liver samples submitted to partial ischemia (IR) or not (NI) were obtained from the same animal. The samples were divided into 7 groups. Data were analyzed statistically by means of the nonparametric Mann-Whitney test and Wilcoxon Matched test, with the level of significance set at 5% (P < .05).

Results

The rate of oxygen consumption by state 3 mitochondria was inhibited in all ischemic groups compared with the sham group (SH vs IR: P = .0052; SH vs IRMB5′: P = .0006; SH vs IRMB15′: P = .0048), which did not occur in the nonischemic contralateral portion of the same liver (SH vs NI: P = .7652; SH vs NIMB5′: P = .059; SH vs NIMB15′: P = .3153). The inhibition of the rate of oxygen consumption by state 3 mitochondria was maintained in the presence of MB (IR vs IRMB5′: P = .4563; IR vs IRMB15′: P = .9021). The respiratory control ratio was reduced in all ischemic groups compared with the sham group, owing to the inhibition of oxygen consumption in state 3 (SH vs IR: P = .0151; SH vs IRMB5′: P = .005; SH vs IRMB15′: P = .0007).

Conclusions

Methylene blue had no effect on the mitochondrial respiratory parameters studied, but was able to reduce lipid peroxidation, preventing the production of reactive oxygen species (SH vs IRMB15′: P = .0210).