Impact of Boldine Treatment on Hypertrophy and Lipid Peroxidation in the Right Ventricle Subjected to Experimental Adrenergic Overstimulation.

Abstract

Abstract: Adrenergic overstimulation is detrimental to the left ventricle. However, its effects on the right ventricle (RV) are not clear. Because adrenergic overload increases metabolic demand and oxidative stress, boldine could be a therapeutic option in the treatment of cardiovascular disease because of its antioxidant role. This study aimed to investigate the impact of adrenergic overload on RV remodeling and the cardioprotective effect of boldine. Animals were divided into 4 groups: control (C), boldine (25 mg/kg i. P .) (B), isoproterenol (ISO) (5 mg/kg subcutaneously), and boldine+isoproterenol (B+ISO). Echocardiography, Fulton index (FI), histology, oxidative stress, inflammation, and β-adrenergic receptor (ADR) were analyzed. The diastolic parasternal length [C 0.698 (0.623-0.724) versus ISO 0.77 (0.73-0.81)], FI [C 0.268 (0.231-0.275) versus ISO 0.340 (0.280-0.353)], inflammatory infiltration (∼40%), and ADR [C 0.78 (0.71-0.84) versus ISO 1.74 (1.52-2.00)] were increased in the ISO group ( P < 0.05). Boldine treatment (B+ISO) reduced the FI [0.240 (0.228-0.263)], lipid peroxidation [2.07 (2.01-2.61)], and ADR [0.71(0.62-0.80)]. Boldine increased total SH levels in B+ISO [C 2.4 (1.78-2.71); ISO 4.01 (2.95-4.66) versus B+ISO 6.77(5.15-8.60)] ( P < 0.05). There was a positive correlation between lipid peroxidation and the FI, and a negative correlation between total SH and the FI ( P < 0.05). This is the first study to explore the effects of adrenergic overstimulation on RV and the protective effect of boldine. Such data pave the way for further research involving RV remodeling, such as in pulmonary hypertension, and a new therapeutic option.