Abstract
Bile acids (BA) are recognized by their role in nutrient absorption. However, there is growing evidence that BA also have endocrine and metabolic functions. Besides, the steroidal-derived structure gives BA a toxic potential over the biological membrane. Thus, cholestatic disorders, characterized by elevated BA on the liver and serum, are a significant cause of liver transplant and extrahepatic complications, such as skeletal muscle, central nervous system (CNS), heart, and placenta. Further, the BA have an essential role in cellular damage, mediating processes such as membrane disruption, mitochondrial dysfunction, and the generation of reactive oxygen species (ROS) and oxidative stress. The purpose of this review is to describe the BA and their role on hepatic and extrahepatic complications in cholestatic diseases, focusing on the association between BA and the generation of oxidative stress that mediates tissue damage.
Highlights
Bile acids (BA) are a group of steroidal molecules derived from cholesterol
Several receptors are associated with BAdependent actions, such as farnesoid X receptor (FXR), TGR5, sphingosine-1-phosphate receptor 2 (S1PR2), pregnane X receptor (PXR), constitutive androstane receptor (CAR), and vitamin D receptor (VDR)
The FXR receptor has a central role in BA physiology and carbohydrate and lipid homeostasis
Summary
Bile acids (BA) are a group of steroidal molecules derived from cholesterol. These molecules have been historically described as solubilizing agents for lipids and activators for pancreatic enzymes, supporting their role in intestinal absorption [1, 2]. Cholestatic liver diseases and the complications derived from the gradual destruction of bile ducts produce BA accumulation in the liver This increment of BA induces a proinflammatory response and an increased production of reactive oxygen species (ROS), leading to cellular damage. Endogenous or xenobiotic-induced, might generate the obstruction of bile flow, elevating the BA concentrations within hepatocytes and serum and damaging the neighboring tissues [6, 8, 9]. In this line, the BA-dependent cytotoxicity and cellular alterations are associated with oxidative stress, mainly affecting the liver and extrahepatic tissues such as the heart, skeletal muscle, and placenta. In the central nervous system (CNS), contradictory effects of BA and their receptors reportedly show generation or prevention of oxidative stress [10,11,12]
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