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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Re-Wiring the Circuit: Mitochondria as a Pharmacological Target in Liver Disease

Author(s): C. V. Diogo, I. Grattagliano, P. J. Oliveira, L. Bonfrate and P. Portincasa

Volume 18 , Issue 35 , 2011

Page: [5448 - 5465] Pages: 18

DOI: 10.2174/092986711798194432

Price: $65

Abstract

Mitochondria play a key role in intracellular energy-generating processes, cell life and death, and are heavily involved in several metabolic pathways by integrating signaling networks; thus, a very large number of conditions are characterized by mitochondrial bioenergetic in humans. Often, mitochondrial changes are directly or indirectly dependent on the activation of intracellular stress cascades or death receptor-mediated pathways. Reactive oxygen species (ROS) formation, glutathione (GSH) depletion, protein alkylation and respiratory complex alterations are major events associated with mitochondrial dysfunction and represent critical initiating events in most forms of chronic liver disease.

Through creating an analogy with a disrupted electric circuit gone bad, the present review focuses initially on how hepatic mitochondrial bioenergetics is affected in the context of drug and disease-induced liver failure and how targeting mitochondria with several antioxidant agents can be helpful for preventing the disruption of the mitochondrial electric circuit.

Keywords: Alcohol, cholestasis, drug-induced liver injury, ischemia-reperfusion, glutathione, liver diseases, medicinal chemistry, reactive oxygen species, oxidative stress, pharmacology, mitochondria


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