Therapeutic effect of bezafibrate against biliary damage: a study of phospholipid secretion via the PPARalpha-MDR3 pathway
| Autor: | Akinobu Taketomi, Tsuyoshi Yoshimoto, Motoyuki Kohjima, Manabu Nakashima, Makoto Nakamuta, Tatsuya Fujino, Kazuhiro Kotoh, Naohiko Harada, Yoshihiko Maehara, Munechika Enjoji, Nobito Higuchi, Masaki Kato, Kazuyuki Machida, Masayoshi Yada, Ryoko Yada, Kenichiro Yasutake, Kazuhisa Matsunaga, Takuya Nishinakagawa |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B digestive system Polymerase Chain Reaction chemistry.chemical_compound Primary biliary cirrhosis Cholestasis Internal medicine medicine Humans Pharmacology (medical) PPAR alpha Gamma-glutamyltransferase Phospholipids Aged Hypolipidemic Agents Pharmacology Aged 80 and over Bezafibrate biology Cholesterol business.industry Liver Cirrhosis Biliary Hepatobiliary disease Fatty liver gamma-Glutamyltransferase Jaundice Middle Aged medicine.disease Alkaline Phosphatase digestive system diseases Fatty Liver Jaundice Obstructive Endocrinology chemistry biology.protein Drainage Female medicine.symptom business medicine.drug |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 48(1) |
| ISSN: | 0946-1965 |
| Popis: | Objective Bezafibrate (BF) has been used to treat biliary damage, particularly in patients with primary biliary cirrhosis (PBC), and its clinical efficacy has been demonstrated. The mechanism of action is thought to involve activation of the PPARalpha-MDR3-phospholipid (PL) secretion pathway. We tried to confirm this hypothesis in patients with hepatobiliary disease. Methods The levels of serum gamma-glutamyl transpeptidase and alkaline phosphatase, and those of bile components were examined before and after BF administration in patients with obstructive jaundice undergoing percutaneous transhepatic biliary drainage (PTBD). Hepatic expression of PPARalpha and MDR3 was quantified by real-time PCR in patients with PBC or non-alcoholic fatty liver disease (NAFLD). Results In patients with obstructive jaundice, BF decreased the serum levels of biliary enzymes and increased the bile concentration of PL. In patients with PBC or NAFLD, the expression levels of MDR3 were already up-regulated before starting the BF treatment. Although BF treatment did not further up-regulate MDR3 expression in NAFLD patients, PPARalpha expression was significantly increased. Conclusions BF enhanced the secretion of PL into bile in cholestatic patients undergoing PTBD. However, in patients with PBC or NAFLD, diseases that represent cholesterol overload, MDR3 was already expressed at a high level to compensate for bile acids overproduction, and its expression was hardly affected by BF. In patients with chronic liver diseases such as PBC, BF may induce clinical effects via mechanisms independent of PL secretion. |
| Databáze: | OpenAIRE |
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