NDLI: Effects of simvastatin, atorvastatin, ezetimibe, and ezetimibe + simvastatin combination on the inflammatory process and on the liver metabolic changes of arthritic rats.

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Effects of simvastatin, atorvastatin, ezetimibe, and ezetimibe + simvastatin combination on the inflammatory process and on the liver metabolic changes of arthritic rats.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bracht, Lívia Barbosa, Carmem Patrícia Caparroz-Assef, Silvana Martins Cuman, Roberto Kenji Nakamura Ishii-Iwamoto, Emy Luiza Bracht, Adelar Bersani-Amado, Ciomar Aparecida
Description	Country affiliation: Brazil Author Affiliation: Bracht L ( Laboratory of Inflammation, Department of Pharmacy and Pharmacology, University of Maringá, 87.020.900 Maringá, Paraná, Brazil.)
Abstract	In this study, simvastatin, atorvastatin, ezetimibe, and ezetimibe + simvastatin combination were administered to arthritic rats, first to determine their effects on the inflammatory response, employing a low-dose adjuvant-induced arthritis model in rats. Arthritis was induced by the subcutaneous injection of a suspension of Mycobacterium tuberculosis (100 µg) in mineral oil [complete Freund's adjuvant used (CFA)] into the plantar surface of the hind paws. Simvastatin(40 mg/kg), atorvastatin(10 mg/kg), ezetimibe(10 mg/kg), ezetimibe(10 mg/kg) + simvastatin(20 mg/kg or 40 mg/kg) were given intragastrically and the treatment began on the day of CFA injection and continued daily up to the 28th day after arthritis induction. The ezetimibe + simvastatin combination was more effective in reducing the inflammatory response in arthritic rats than in atorvastatin, simvastatin, or ezetimibe monotherapy. The observed effect seems to be cholesterol-independent as there were no changes in plasma cholesterol levels. In spite of the benefits on joint lesions, treatment with ezetimibe + simvastatin combination caused a marked increment in liver, kidneys, spleen size, and plasma transaminases activities. Therefore, animals treated with the ezetimibe(10 mg/kg) + simvastatin(40 mg/kg) combination were also submitted to liver perfusion experiments. In this regard, ezetimibe + simvastatin did not improve the liver metabolic alterations seen in control arthritic rats, on the contrary, a worsening was observed in liver production of glucose from alanine, as well as in oxygen uptake. All of these metabolic changes appear to be induced by treatment with ezetimibe + simvastatin combination, as the same metabolic effects were observed in normal and treated arthritic animals.
File Format	HTM / HTML
ISSN	07673981
Issue Number	6
Volume Number	26
e-ISSN	14728206
Journal	Fundamental & Clinical Pharmacology
Language	English
Publisher	Wiley
Publisher Date	2012-12-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Pharmacology Anti-inflammatory Agents Therapeutic Use Arthritis, Experimental Drug Therapy Azetidines Heptanoic Acids Liver Metabolism Pyrroles Simvastatin Animals Administration & Dosage Adverse Effects Blood Atorvastatin Calcium Drug Therapy, Combination Ezetimibe Leukocyte Count Leukocytes Cytology Drug Effects Enzymology Liver Function Tests Perfusion Rats Rats, Sprague-dawley Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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