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Review
, 60 (7), 697-706

Brain Energy Metabolism and Mitochondrial Dysfunction in Acute and Chronic Hepatic Encephalopathy

Affiliations
Review

Brain Energy Metabolism and Mitochondrial Dysfunction in Acute and Chronic Hepatic Encephalopathy

Kakulavarapu V Rama Rao et al. Neurochem Int.

Abstract

One proposed mechanism for acute and chronic hepatic encephalopathy (HE) is a disturbance in cerebral energy metabolism. It also reviews the current status of this mechanism in both acute and chronic HE, as well as in other hyperammonemic disorders. It also reviews abnormalities in glycolysis, lactate metabolism, citric acid cycle, and oxidative phosphorylation as well as associated energy impairment. Additionally, the role of mitochondrial permeability transition (mPT), a recently established factor in the pathogenesis of HE and hyperammonemia, is emphasized. Energy failure appears to be an important pathogenetic component of both acute and chronic HE and a potential target for therapy.

Figures

Figure 1
Figure 1
Effect of cyclosporin A (CsA, 5 µM), an inhibitor of the mPT, on ammonia-induced release of lactate in cultured astrocytes. Following treatment of ammonia (5 mM NH4Cl, 24 h), culture medium was collected and lactate levels in the media were determined by an enzymatic assay employing lactate dehydrogenase that converts lactate to pyruvate (Kala and Hertz, 2005). Values are mean ± SEM of 10 individual plates in each experimental group obtained from two different seedings. * vs. control, p<0.01; ** vs. ammonia (NH4), p<0.01.
Figure 2
Figure 2
A. Effect of Ro5–4864 (10 nM) and PK11195 (10 nM), agonist and antagonist of TSPO, respectively, on the dissipation of inner mitochondrial membrane potential (ΔΨm) (24 h) in cultured astrocytes. The ΔΨm was measured by incubating (15 min) cultures with a tetramethyl-rhodamine ethyl-ester (TMRE, 25 nM), a potentiometric fluorescent dye commonly employed to determine ΔΨm (Rama Rao et al, 2005a; 2005b). Treatment with Ro5–4864 (Ro5) significantly dissipated the ΔΨm as shown by a reduction in TMRE fluorescence, whereas PK 11195 (PK) had no effect. Scale bar = 100 µm. B. Quantitation of TMRE fluorescence. Values are mean ± SEM of the total number of mean pixel values in each experimental group. * vs. control (C), p<0.01.
Figure 3
Figure 3
A. Effect of tetrahydroprogesterone (THP; 10 nM) and tetrahydrodeoxycorticosterone (THDOC; 10 nM), alone or in combination with ammonia (5 mM NH4Cl), on the dissipation of inner mitochondrial membrane potential (ΔΨm) (24 h) in cultured astrocytes as measured by TMRE fluorescence. Both THP and THDOC significantly dissipated the ΔΨm and such dissipation was potentiated in the presence of ammonia. Scale bar = 100 µm. B. Quantitation of TMRE fluorescence. Values are expressed as mean ± standard error of mean (SEM) of the total number of mean pixel values derived from 15 randomly captured image fields from each culture plate (total of 6 plates) obtained from 2 separate seedings. * vs. control (C), p<0.01; ** vs. THP and THDOC, p<0.05.
Figure 3
Figure 3
A. Effect of tetrahydroprogesterone (THP; 10 nM) and tetrahydrodeoxycorticosterone (THDOC; 10 nM), alone or in combination with ammonia (5 mM NH4Cl), on the dissipation of inner mitochondrial membrane potential (ΔΨm) (24 h) in cultured astrocytes as measured by TMRE fluorescence. Both THP and THDOC significantly dissipated the ΔΨm and such dissipation was potentiated in the presence of ammonia. Scale bar = 100 µm. B. Quantitation of TMRE fluorescence. Values are expressed as mean ± standard error of mean (SEM) of the total number of mean pixel values derived from 15 randomly captured image fields from each culture plate (total of 6 plates) obtained from 2 separate seedings. * vs. control (C), p<0.01; ** vs. THP and THDOC, p<0.05.

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