Bile acids, oxidative stress, and renal function in biliary obstruction.
Renal dysfunction occurs in patients with biliary obstruction. Plasma accumulation of bile acids and oxidative stress have been proposed as contributory factors. Bile acids can alter the renal handling of electrolytes and water by blocking the Na(+)-H+ antiport in the tubule. Oxidative stress, defined as an imbalance between radical generating systems and radical scavenging systems giving rise to free radical induced tissue damage, occurs in patients with liver disease. Bile acids cause oxidative damage to tubular cell membranes by stimulating the generation of oxygen free radicals from mitochondria, as well as promoting their release from neutrophils and macrophages. Oxidative stress can promote the formation of a variety of vasoactive mediators including endothelin-1, cysteinyl leukotrienes, as well as the F2-isoprostanes, endogenous products of lipid peroxidation. These mediators can each affect renal function directly by causing renal vasoconstriction or decreasing the glomerular capillary ultrafiltration coefficient, and thus reduce glomerular filtration rate. Collectively, these factors contribute to the onset of renal failure in patients with biliary obstruction.
Bomzon
A
A
Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Holt
S
S
Moore
K
K
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000737:chemistry; D001651:Cholestasis, Extrahepatic / Q000150:complications* / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology*; D007677:Kidney Function Tests; D018384:Oxidative Stress
D001647:Bile Acids and Salts