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Updated: May 15, 2026

Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
Methylene blue protects liver oxidative capacity after gut ischaemia-reperfusion in the rat
O Collange1, A-L Charles, J Bouitbir
1Pôle Anesthésie, Réanimation Chirurgicale, SAMU, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. Olivier.collange@chru-strasbourg.fr
Objectives:
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.
Design:
Controlled animal study.
Materials And 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.
Insights
Gut ischemia/reperfusion (IR) impairs liver mitochondria function. Methylene blue (MB) treatment protected against this dysfunction, preserving oxidative activity and preventing liver damage in an animal model.
Area of Science:
- Hepatology
- Mitochondrial Physiology
- Surgical Research
Background:
- Mesenteric ischemia/reperfusion (IR) can lead to liver mitochondrial dysfunction and multiple organ failure.
- Early detection and intervention are crucial for managing IR-induced organ damage.
Purpose of the Study:
- To investigate if gut IR causes early impairment of liver mitochondrial oxidative activity.
- To determine if methylene blue (MB) offers protection against gut IR-induced liver mitochondrial dysfunction.
Main Methods:
- A controlled animal study involving rats subjected to mesenteric IR.
- Groups included controls, gut IR, and gut IR treated with MB.
- Assessment of liver function markers, lactate, histology, apoptosis, and liver mitochondrial respiration (state 3, complexes II-IV activity).
Main Results:
- Gut IR significantly increased liver enzymes and lactate levels, causing intestinal damage and apoptosis.
- Liver mitochondrial state 3 respiration decreased by 30% and respiratory chain complex activities were reduced post-IR.
- Impaired liver mitochondrial respiration correlated with elevated blood lactate levels.
- Methylene blue administration restored liver mitochondrial function.
Conclusions:
- Gut IR induces early liver mitochondrial dysfunction.
- Methylene blue (MB) demonstrates protective effects against IR-induced liver mitochondrial impairment.
