Ebselen protects against the reduction in levels of drug-metabolizing enzymes in livers of rats with deoxycholic acid-induced liver injury.
Ebselen is a seleno-organic compound that inhibits oxidative stress by lipid peroxidation through a glutathione peroxidase-like activity. We studied the effect of ebselen on the expression of hepatic drug-metabolizing enzymes in rats with deoxycholic acid-induced liver injury. Hydrophobic bile acids, such as deoxycholic acid, are known to cause cholestatic liver injury, and it was reported that expression of hepatic cytochrome P-450 (CYP) was reduced by deoxycholic acid administration in rats. Hydrophobic bile acids induce lipid peroxidation in the liver, and this may be one mechanism of the development of liver injury. In the present study, we investigated the effect of ebselen (30 mg/kg/day for 10 days) on rats ingesting deoxycholic acid (1% of diet for 10 days). Deoxycholic acid decreased levels of CYP1A1, 2B1, 2E1 and 3A2 to 34, 58, 62 and 37% of control values, respectively, and increased serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) activities to 1.8 and 8.6 times the levels of controls, respectively. Administration of ebselen with deoxycholic acid prevented the decreases in levels of CYP1A1 and 3A2 (86 and 65% of control, respectively) and the increases in serum ALP and ALT activities (1.4 and 1.9 times of control, respectively) caused by deoxycholic acid. These results indicate that ebselen may have a protective effect against hydrophobic bile acid-induced liver injury.
Tanaka
Masami
M
Department of Pharmacology, St Marianna University School of Medicine, Kawasaki, Japan. m3tanaka@marianna-u.ac.jp
Takezawa
Nahomi
N
Kumai
Toshio
T
Watanabe
Minoru
M
Matsumoto
Naoki
N
Nakaya
Sachiko
S
Kobayashi
Shinichi
S
D000410:Alanine Transaminase / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001393:Azoles / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003840:Deoxycholic Acid / Q000009:adverse effects; D054833:Isoindoles; D008297:Male; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; D003840:Deoxycholic Acid; C042986:ebselen; D003577:Cytochrome P-450 Enzyme System; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase