Cardioprotective effect of cerium oxide nanoparticles in monocrotaline rat model of pulmonary hypertension: A possible implication of endothelin-1

Abstract

Aims: Cerium oxide nanoparticles (CeO₂NPs) have been recently introduced into the medical field for their antioxidant properties. The ability of CeO₂NPs alone or in combination with spironolactone (SP) to attenuate monocrotaline (MCT)-induced pulmonary hypertension and associated right ventricular hypertrophy was studied in rats. A special emphasis was given to endothelin-1 pathway.

Materials and methods: Pulmonary hypertension was induced in albino rats by a single subcutaneous injection of MCT (60 mg/kg). Rats received either single CeO₂NPs therapy or combined therapy with SP for 2 weeks.

Key findings: CeO₂NPs improved pulmonary function tests with concomitant decrease in serum endothelin-1 and pulmonary expression of endothelin-1 and its receptor ETAR. Besides, CeO₂NPs diminished MCT-induced right ventricular hypertrophy and reduced cardiac oxidative stress and apoptosis.

Significance: CeO₂NPs could improve pulmonary hypertension and associated right ventricular hypertrophy with no additive value for SP. Besides being an antioxidant, CeO₂NPs work through endothelin-1 pathway to improve pulmonary hypertension.

Keywords: Cerium oxide nanoparticles; Endothelin-1; Pulmonary hypertension; Right ventricular hypertrophy; Spironolactone.