Ethanol induced mitochondria injury and permeability transition pore opening: Role of mitochondria in alcoholic liver disease

AIM: To observe changes of mitochondria and investigate the effect of ethanol on mitochondrial permeability transition pore (PTP), mitochondrial membrane potential (MMP, Delta Psi m) and intracellular calcium concentration in hepatocytes by establishing an animal model of alcoholic liver disease (ALD). METHODS: Forty adult male Wistar rats were randomly divided into two groups, the model group (20) was administered alcohol intragastrically plus an Olive oil diet to establish an ALD model, and the control group (20) was given an equal amount of normal saline. The ultramicrostructural changes of mitochondria were observed under electron microscopy. Mitochondria of liver was extracted, and patency of PTP, mitochondrial membrane potential (Delta Psi m), mitochondrial mass and intracellular calcium concentration of isolated hepacytes were detected by flow cytometry using rhodamine123 (Rh123), Nonyl-Acridine Orange and calcium fluorescent probe Fluo-3/AM, respectively. RESULTS: Membrane and cristae were broken or disappeared in mitochondria in different shapes under electron microscopy. Some mitochondria showed U shape or megamitochondrion. In the model group, liver mitochondria PTP was broken, and mitochondria swelled, the absorbance at 450 nm, A540 decreased (0.0136 +/- 0.0025 vs 0.0321 +/- 0.0013, model vs control, P < 0.01); mitochondria transmembrane potential (239.4638 +/- 12.7263 vs 377.5850 +/- 16.8119, P < 0.01) was lowered; mitochondrial mass (17.4350 +/- 1.9880 vs 31.6738 +/- 3.4930, P < 0.01); and [Ca2+](i) was increased in liver cells (7.0020 +/- 0.5008 vs 10.2050 +/- 0.4701, P < 0.01). CONCLUSION: Chronic alcohol intake might lead to broken mitochondria PTP, decreased mitochondria membrane potential and injury, and elevated intracellular Ca2+ production. Ethanol-induced chondriosome injury may be an important mechanism of alcoholic diseases. (C) 2007 The WJG Press. All rights reserved.