913 - Rabdomiosarcoma. Bezafibrato induz miotoxicidade em

ca-0290.pdf
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http://www.medicinacomplementar.com.br/convertido/ca-0290.htm
Rabdomiosarcoma. Bezafibrato induz miotoxicidade em células do
rabdomiosarcoma embrionário humano via ativação do PPAR-alfa
28/09/10
A toxicidade muscular do bezafibrato é aumentada com o uso concomitante da atorvastatina o que provoca aumento da apoptose
via ativação da via Akt. Muitos pacientes portadores de aumento de colesterol e triglicérides estão ingerindo a combinação bezafibrato
e estatina prescritas pelo cardiologista. Sentem dores musculares e não sabem por quê. Apresentam toxicidade muscular com
aumento do CPK e continuam tomando a associação, enquanto existem muitas estratégias sem efitos colaterais para diminuir o
colesterol e os triglicérides.
José de Felippe Junior
Bezafibrate induces myotoxicity in human rhabdomyosarcoma cells via peroxisome proliferator-activated receptor alpha
signaling.
Zhao Y, Okuyama M, Hashimoto H, Tagawa Y, Jomori T, Yang B. Toxicol In Vitro. 2010 Feb;24(1):154-9.
Department of Nutrition and Food, Harbin Medical University, Heilongjiang, China. [email protected]
Abstract
Fibrates, the ligands of peroxisome proliferator-activated receptor alpha (PPARalpha), are used as a class of lipid-lowering drugs in
clinical practice for the treatment of dyslipidemia. Fibrates are well tolerated in most cases concomitantly with occasional adverse
reactions including muscular toxicity, which is enhanced by the combination with statins. This study was designed to investigate the
effects of bezafibrate as a PPARalpha agonist on human embryo rhabdomyosarcoma (RD) cells and possible mechanisms responsible
for bezafibrate-mediated myopathy. The results revealed that bezafibrate caused a dose-dependent decrease in cell viability,
which was fortified in association with atorvastatin at a pharmacological dose. Bezafibrate at toxic doses of 300 and 1000microM
upregulated PPARalpha at the mRNA level, counteracted by a PPARalpha antagonist (MK886). Bezafibrate at a toxic dose induced typical
apoptotic characteristics related to the inhibition of phosphorylation of Akt which was blocked by PPARalpha antagonist. Toxic doses
of bezafibrate initiated a significant increase in pyruvate dehydrogenase kinase 4 mRNA and protein levels, compromised by MK886.
These results suggest the critical roles of PPARalpha signaling in bezafibrate-induced myotoxicity and the involvement of apoptosis
through Akt pathway.
PMID: 19683050
30/9/2011 15:16