RESUMO
Doxorubicin (Dox), an effective antineoplastic drug, was limited use for cardiotoxicity. Xinshuitong Capsule (XST), a patented herbal formula, showed desirable beneficial effects in the treatment of chronic heart failure (CHF) patients. However, the drug on Dox-induced cardiotoxicity remains unclear. Ninety male Sprague-Dawley rats were randomized into two groups: 15 rats were selected as the normal group and 75 rats were injected intraperitoneally with Dox to establish CHF rat models, the success ones were randomly divided into five groups: low XST (LXST), medium XST (MXST) or high XST (HXST) (4.9, 9.8, or 19.6 g/kg d) administrated intragastrically twice a day for 4 weeks, with the captopril-treated group and the model group as comparison. The model group showed the cardiac functions generally impaired, and CHF mortality rate higher (47%) than those in the XST-treated groups (averaged 24%, P < 0.05). Compared with XST-treated groups, myocardial remodeling, inflammation and desarcomerization, and higher water content more severe in the cardiac tissue in the model group (P < 0.05), which was associated with higher expressions of mRNA or protein levels of AQP1, 4 and 7. Dox-impaired cardiac functions, cardiac remodeling and myocardial edema could be dose-dependently reverted by XST treatment. XST could inhibit AQP1, 4 and 7 at mRNA levels or at protein levels, which was associated with the attenuation of myocardial edema and cardiac remodeling, decreasing the ventricular stiffness and improving the cardiac functions and rats' survival. AQPs is involved in cardiac edema composed one of the mechanisms of Dox-induced cardiotoxicity, XSTvia inhibition of AQPs relieved the Dox-induced side effects.
Assuntos
Aquaporinas/antagonistas & inibidores , Medicamentos de Ervas Chinesas/farmacologia , Edema Cardíaco/prevenção & controle , Insuficiência Cardíaca/prevenção & controle , Miocárdio/metabolismo , Administração Oral , Animais , Aquaporina 1/antagonistas & inibidores , Aquaporina 1/genética , Aquaporina 1/metabolismo , Aquaporina 4/antagonistas & inibidores , Aquaporina 4/genética , Aquaporina 4/metabolismo , Aquaporinas/genética , Aquaporinas/metabolismo , Água Corporal/metabolismo , Cápsulas , Cardiotoxicidade , Doença Crônica , Modelos Animais de Doenças , Doxorrubicina , Medicamentos de Ervas Chinesas/administração & dosagem , Edema Cardíaco/induzido quimicamente , Edema Cardíaco/metabolismo , Edema Cardíaco/patologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Masculino , Miocárdio/patologia , Ratos Sprague-Dawley , Transdução de Sinais , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacosRESUMO
Argemone seeds are mixed with mustard seeds either accidentally or purposefully, and, ingestion of this contaminated oil can lead to often fatal "epidemic dropsy". The liver, heart, kidney and lungs are the major target organs of the toxins (the alkaloids, sanguinarine and dihydrosanguinarine) and damage is mostly caused by free radical (singlet oxygen and hydroxyl radical) to the cell membranes. Treatment at present is mainly symptomatic but therapy with anti-secretory agents for glaucoma and anti-oxidants/free radical scavengers for systemic manifestations appear to be logical.