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01 November 2010

Taxol, a microtubule stabilizer, prevents atrial fibrillation in in vitro atrial fibrillation models using rabbit hearts

Junjie XiaoABCD, Hong ZhangBCE, Dandan LiangBDF, Ying LiuCF, Yi LiuDF, Hong ZhaoCF, Jun LiCEF, Luying PengAEF, Yi-Han ChenAEFG

Med Sci Monit 2010; 16(11): BR353-360 :: ID: 881213

Abstract

Background: Increased atrial oxidative stress plays an important role in the pathogenesis of atrial fibrillation. A predisposition for atrial fibrillation can be produced by altering the activities of enzymes related to reactive oxygen species metabolism. Microtubule integrity is necessary for cardio-protection; microtubules are involved in many cellular processes, including enzymatic activity. Taxol, a common microtubule stabilizer, can protect cardiac myocytes from oxidative stress. However, its effects on atrial fibrillation remain unknown.
Material/Methods: In vitro rabbit heart models of ischemia-, stretch-, and cholinergic agitation–induced atrial fibrillation were developed. Using either a fluorometric or spectrophotometric assay, we measured reactive oxygen species and the activities of oxidative enzymes including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, mitochondrial electron transport chain complexes I, mitochondrial electron transport chain complexes III, and superoxide dismutase.
Results: Taxol effectively reduced the incidence of ischemia-, stretch- and cholinergic agitation-induced atrial fibrillation in in vitro rabbit heart models by 50%, 60%, and 40%. Moreover, Taxol decreased the level of reactive oxygen species by 46%, 49%, and 70% in ischemia-, stretch- and cholinergic agitation–induced atrial fibrillation models. Additionally, the activities of NADPH oxidase and xanthine oxidase were increased, whereas those of mitochondrial electron transport chain complexes I and III and superoxide dismutase were not affected.
Conclusions: Taxol, a microtubule stabilizer, prevents atrial fibrillation in in vitro atrial fibrillation model using rabbit hearts. This stabilizer most likely prevents atrial fibrillation by reducing the level of reactive oxygen species.

Keywords: Reactive Oxygen Species - metabolism, Rabbits, Random Allocation, Paclitaxel - pharmacology, NADPH Oxidase - metabolism, Myocytes, Cardiac - metabolism, Models, Animal, Microtubules - metabolism, Heart Atria - physiopathology, Electron Transport Complex III - metabolism, Electron Transport Complex I - metabolism, Cholinergic Agents - pharmacology, Cardiotonic Agents - pharmacology, Atrial Fibrillation - prevention & control, Animals, Stress, Mechanical, Superoxide Dismutase - metabolism, Tubulin Modulators - pharmacology, Xanthine Oxidase - metabolism

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