Abstract
Chronic cholestatic conditions are characterized by metabolic alterations in bile salts, lipids, and nutrients, and are associated to membrane lipid destruction and mitochondrial dysfunction. Primary biliary cholangitis, the most common chronic cholestatic condition in humans, is an autoimmune disease characterized by progressive intralobular bile duct destruction. Oxidative and nitrosative stress appear as underlying motors contributing to the ongoing biochemical and morphological changes of the liver. Abnormalities in both nitric oxide metabolism and in redox state of organosulfur (thiol) molecules occur already at early stages, suggesting that such events may have a fundamental pathogenic role in the disease development, and that may potentially be used as diagnostic markers of disease progression. Pharmacological interventions contrasting intra- and extracellular oxidative and nitrosative stress might restore morphological and functional changes. With this objective, ursodeoxycholic acid has been tested to protect against oxidative and nitrosative stress in the early stages of chronic cholestasis.
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