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Fatty Liver and Ischemia/Reperfusion: Are there Drugs Able to Mitigate Injury?

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Fatty livers are more prone to damage caused by ischemia/reperfusion (I/R). Impaired microcirculation, Kupffer cell dysfunction, increased adhesion of leukocytes, impaired mitochondrial function and ATP depletion are probable causes for fatty liver susceptibility. Therefore, hepatic steatosis is a major risk factor for liver surgery and success of transplantation of fatty donor organs. The mechanisms involved in I/R injury are complex and there is no general consensus regarding the sources of ROS generation, nitric oxide (NO) action, the role of tumor necrosis factor-α (TNF-α), and transcription factors, such as nuclear factor kappa B (NFκB). Impairment of mitochondrial function is one of the most important alterations that occur in I/R injury, resulting in the alteration of energy metabolism. Ischemic preconditioning (IPC) and post conditioning (IPost) are adaptive mechanisms against I/R insults that induce intracellular protective responses associated with the preservation of mitochondrial function.

There are several pharmacological drugs and natural derivatives presenting metabolic and/or antioxidant effects that can directly or indirectly protect the liver against I/R injury. While the precise targets and mechanisms are still not totally understood, the mitochondrion presents itself as a major player on mediating these protective events. As so, compounds that are able to improve mitochondrial function and hepatic energetic balance might prove viable candidates when developing new pharmacological approaches that can minimize injury to steatotic livers subjected to I/R events.

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Keywords: ATP; Fatty liver; cell death; compounds; ischemia/reperfusion; microcirculation; mitochondria; mitochondrial permeability transition; oxidative stress; preconditioning

Document Type: Research Article

Publication date: 01 November 2011

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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