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- Title
Effects of simvastatin, atorvastatin, ezetimibe, and ezetimibe + simvastatin combination on the inflammatory process and on the liver metabolic changes of arthritic rats.
- Authors
Bracht, Lívia; Barbosa, Carmem Patrícia; Caparroz-Assef, Silvana Martins; Cuman, Roberto Kenji Nakamura; Ishii-Iwamoto, Emy Luiza; Bracht, Adelar; Bersani-Amado, Ciomar Aparecida
- 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. Simvastatin40mg/kg, atorvastatin10mg/kg, ezetimibe10mg/kg, ezetimibe10mg/kg + simvastatin20mg/kg or 40mg/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 ezetimibe10mg/kg + simvastatin40mg/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.
- Subjects
SIMVASTATIN; ATORVASTATIN; EZETIMIBE; LABORATORY rats; RHEUMATOID arthritis
- Publication
Fundamental & Clinical Pharmacology, 2012, Vol 26, Issue 6, p722
- ISSN
0767-3981
- Publication type
Article
- DOI
10.1111/j.1472-8206.2011.00976.x