Is Liver Enzyme Release Really Associated with Cell Necrosis Induced by Oxidant Stress?

Martha Lucinda Contreras-Zentella,Rolando Hernández-Muñoz

doi:10.1155/2016/3529149

Martha Lucinda Contreras-Zentella, Rolando Hernández-Muñoz

Open Access

https://doi.org/10.1155/2016/3529149

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Abstract

Hepatic diseases are a major concern worldwide. Increased specific plasma enzyme activities are considered diagnostic features for liver diseases, since enzymes are released into the blood compartment following the deterioration of the organ. Release of liver mitochondrial enzymes is considered strong evidence for hepatic necrosis, which is associated with an increased production of ROS, often leading to greater hepatic lipid peroxidation. Lipotoxic mediators and intracellular signals activated Kupffer cells, which provides evidence strongly suggesting the participation of oxidant stress in acute liver damage, inducing the progression of liver injury to chronic liver damage. Elevated transaminase activities are considered as an index marker of hepatotoxicity, linked to oxidant stress. However, a drastic increase of serum activities of liver enzyme markers ought not necessarily to reflect liver cell death. In fact, increased serum levels of cytoplasmic enzymes have readily been observed after partial hepatectomy (PH) in the regenerating liver of rats. In this regard, we are now showing that in vitro modifications of the oxidant status affect differentially the release of liver enzymes, indicating that this release is a strictly controlled event and not directly related to the onset of oxidant stress of the liver.

Highlights

Every organ can elicit a specific pattern of enzyme release, which remains not elucidated
In the case of alcoholic fatty liver disease (AFLD), there is an increase of NADH/NAD+ value promoted by liver alcohol oxidation, which will induce the disorder of fat metabolism, resulting in triglyceride accumulation in hepatocytes [31]
Taking advantage of the model of two-thirds partial hepatectomy- (PH-) induced rat liver regeneration (“smallfor-size liver”), we showed that liver cell proliferation occurs accompanied by a selective Partial hepatectomy- (PH-)induced elevation of serum enzymes, not related to hepatocellular necrosis [93] nor to mitochondrial dysfunction [94]

Summary

Introduction

Every organ can elicit a specific pattern of enzyme release, which remains not elucidated. Release of mitochondrial enzymes from the liver is considered to provide strong evidence for hepatic necrosis [6, 7] and is associated with specific forms of liver disease. It has been shown, for instance, that glutamate dehydrogenase (GDH) correlates well with the presence and extent of necrosis in alcoholic liver disease [8]. The ratio of mitochondrial and total AST (mAST) has been proposed as a marker for chronic alcoholism [9] Both GDH and mAST are widely distributed in various organs and lack specificity as a marker of liver injury. Despite the fact that it was reported that cumulative release of various cytosolic enzymes occurred in proportion to the corresponding activities in human control livers, the mechanisms that govern the release of liver enzymes into the bloodstream are practically unknown

Liver Damage

Oxidant Stress in the Generation of Liver Damage

Effects of Vitamins and Other Antioxidants on Liver Damage

Findings

Conclusions