Effects of simvastatin, ezetimibe, and their combination on histopathologic alterations caused by adjuvant-induced arthritis.
The objective of the present study was to investigate the effects of monotherapy with simvastatin or ezetimibe compared with those of an ezetimibe + simvastatin combination on the histopathologic aspects of arthritis induced by Complete Freund's Adjuvant in rats. The characteristics of diarthrosis were analyzed 7 and 28 days after arthritis induction with regard to the regularity and integrity of articular cartilage, the presence of leukocytes in blood vessels at the inflammation site, and the cytokine levels in articular tissue. Monotherapy with simvastatin or ezetimibe and the ezetimibe + simvastatin combination effectively reduced the cytokine levels (interleukin-6 and tumor necrosis factor) and articular lesions that are characteristic of this experimental disease. Although the results did not reveal significant differences between the monotherapy and the combined therapy, they suggest that these drugs have considerable antiinflammatory properties, as reflected by an attenuation of articular cartilage lesions mediated by a reduction in the levels of proinflammatory cytokines.
Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, PR, Brazil.
Carmem Patrícia
CP
Barbosa
Alessandra Milene
AM
Ritter
Lorena Gimenez
LG
da Silva
Renata
R
Grespan
Roberto Kenji Nakamura
RK
Cuman
Luzmarina
L
Hernandes
Ciomar Aparecida
CA
Bersani-Amado
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D001168:Arthritis / Q000139:chemically induced* / Q000188:drug therapy*; D001384:Azetidines / Q000008:administration & dosage*; D002358:Cartilage, Articular / Q000187:drug effects; D018450:Disease Progression; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005434:Flow Cytometry; D005620:Freund's Adjuvant / Q000009:adverse effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051381:Rats; D019821:Simvastatin / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000924:Anticholesteremic Agents; D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005620:Freund's Adjuvant; D019821:Simvastatin; D000069438:Ezetimibe