Effect of rosuvastatin on cholestasis-induced hepatic injury in rat livers.
Recent studies reported that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have pleotropic effects independent of their lipid-lowering properties. The present study was undertaken to determine whether treatment with rosuvastatin (RO) would be beneficial in a rat model of bile duct ligation (BDL). Animals were divided into three groups: a sham group (group I), a BDL group treated with vehicle (group II), and a BDL group treated with RO (10 mg/kg) (group III). Serum levels of total bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase, and aspartate aminotransferase decreased significantly in group III when compared to group II. Lipid peroxides and NO levels of group III were found to be significantly lower than those of group II. Antioxidant enzymes (superoxide dismutase, glutathione-S-transferase, and catalase) activity in liver tissues markedly decreased in group II, whereas treatment with RO preserved antioxidant enzyme activity. DT-diaphorase activity in group II was significantly higher than that in group III. The histopathological results showed multiple numbers of newly formed bile ductules with inflammatory cells infiltration in group II. These pathological changes were improved in group III. Our data indicate that RO ameliorates hepatic injury, inflammation, lipid peroxidation and increases antioxidant enzymes activity in rats subjected to BDL. RO may have a beneficial effect on treatment of cholestatic liver diseases.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University (Girls), Nasr City, Cairo 11884, Egypt.
Azza S
AS
Awad
Rehab
R
Kamel
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002374:Catalase / Q000378:metabolism; D002779:Cholestasis / Q000150:complications*; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D005982:Glutathione Transferase / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008111:Liver Function Tests; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
D000975:Antioxidants; D005464:Fluorobenzenes; D011743:Pyrimidines; D013449:Sulfonamides; D009569:Nitric Oxide; D000068718:Rosuvastatin Calcium; D002374:Catalase; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin