Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension.
Kolli MB; Manne NDPK; Para R; Nalabotu SK; Nandyala G; Shokuhfar T; He K; Hamlekhan A; Ma JY; Wehner PS; Dornon L; Arvapalli R; Rice KM; Blough ER
Biomaterials 2014 Dec; 35(37):9951-9962
Cerium oxide (CeO2) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO2 nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO2 nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO2 groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO2 nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO2 nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, ß-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO2 nanoparticle administration may attenuate the hypertrophic response of the heart following PAH.
Nanotechnology; Cerium-compounds; Antioxidants; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Animals; Laboratory-animals; Cardiopulmonary-system; Cardiopulmonary-function; Heart; Proteins; Hypertension;
Author Keywords: Cerium oxide nanoparticles; Monocrotaline; Pulmonary arterial hypertension; Right ventricular hypertrophy
Eric R. Blough, Center for Diagnostic Nanosystems, Room 241R, Robert C. Byrd Biotechnology Science Center Building, Department of Pharmaceutical Science and Research, 1700 3rd Ave., Marshall University, Huntington, WV 25755-1090