RESUMEN
Estrogen is known to exhibit cardioprotective and antihyperlipidemic action. Valproic acid has been shown to upregulate estrogen receptors (ERs) in breast and prostate cancer tissues. No pharmacological evaluations for magnesium valproate (MgV) so far have been done for diabetic cadio-lipidemic complications. Based on the above context, current study was undertaken to evaluate the therapeutic effectiveness of MgV in cardiac complications associated with type-1 diabetes mellitus in rats wherein diabetes was induced by single tail vein injection of streptozotocin (STZ, 45mg/kg, IV) in female Sprague Dawley rats and treatment of MgV (210mg/kg, PO) was given for eight weeks to diabetic animals, after which, various biochemical and cardiac biomarkers, hypertrophic, hemodynamic and histological parameters along with immunohistochemistry of ERs in the left ventricle (LV) were estimated. MgV treatment significantly controlled hyperglycemia and dyslipidemia, reduced elevated cardiac biomarkers and C-reactive protein(CRP), significantly improved hemodynamic functions and increased the rate of pressure development and decay. MgV also significantly reduced left ventricular hypertrophy index and cardiac hypertrophy index, LV wall thickness, LV collagen, cardiomyocyte diameter and prevented the oxidative stress with significant increase in Na+-K+-ATPase activity in LV. Moreover, MgV reversed STZ-induced histological alterations and decreased glycogen content in LV and increased the ERß expressions in LV as evidenced by immunohistochemistry. The result indicated that MgV prevented disease progression in the early stage of diabetic cardiomyopathy which seems to be mediated by upregulation of estrogen receptors in LV tissue.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Cardiomiopatías Diabéticas/prevención & control , Ácido Valproico/farmacología , Animales , Cardiomegalia/etiología , Cardiomegalia/prevención & control , Diabetes Mellitus Tipo 1/complicaciones , Progresión de la Enfermedad , Dislipidemias/tratamiento farmacológico , Femenino , Hiperglucemia/tratamiento farmacológico , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Estrógenos/efectos de los fármacos , Receptores de Estrógenos/metabolismo , Estreptozocina , Regulación hacia ArribaRESUMEN
Intravenously administered nanocarriers are widely studied to improve the delivery of various therapeutic agents. However, recent in vivo studies have demonstrated that intravenously administered nanocarriers that do not contain any drug may affect cardiovascular function. Here we provide an example where the drug and the nanocarrier both affect the same cardiovascular parameters following intravenous administration. The peptide ghrelin antagonist (GhA) increases arterial pressure, while thermally hydrocarbonized porous silicon nanoparticles (THCPSi) transiently decrease it, as assessed with radiotelemetry in conscious rats. As a result, intravenous administration of GhA-loaded THCPSi nanoparticles partially antagonized GhA activity: arterial pressure was not increased. When the cardiovascular effects of GhA were blocked with atenolol pretreatment, GhA-loaded nanoparticles reduced arterial pressure to similar extent as drug-free nanoparticles. These data indicate that the biological activity of a drug delivered within a nanocarrier may be obscured by the biological responses induced by the nanocarrier itself.