Melatonin administration protects the right ventricle from adrenergic stress via anti-inflammatory and anti-apoptotic...

Adrenergic overload is a central feature of cardiovascular diseases, contributing to right ventricular (RV) injury. Although widely studied, limited data are available on melatonin's impact on the RV and extracardiac tissues.

To investigate the effects of melatonin on RV remodeling, inflammation, and oxidative stress in the lung and gastrocnemius muscle of rats subjected to isoproterenol (ISO)-induced adrenergic stress.

Male Wistar rats were divided into Control, ISO, and ISO + melatonin groups. ISO (5 mg/kg, s.c.) was administered for 7 days, and ISO + M received ISO plus melatonin (10 mg/kg/day, gavage). Control animals received saline (s.c) and the non-treated groups received only saline by gavage. Cardiac function and hypertrophy was assessed by echocardiography and morphometric analyses, respectively. RV inflammation and fibrosis were examined histologically, while protein expression in the RV (TLR4, NF-κB, Bax) and lungs (eNOS, ETAR) was analyzed by western blotting. Oxidative stress markers (ROS, TBARS, sulfhydryl groups, nitrite) were measured in lung and gastrocnemius.

ISO reduced cardiac output and heart rate, effects preserved by melatonin. RV hypertrophy induced by ISO was not prevented, but inflammatory infiltrate, fibrosis, and upregulation of TLR4, NF-κB, and Bax were attenuated by melatonin. In the lungs, no significant alterations were observed, except for increased nitrite levels in ISO + M. Gastrocnemius oxidative stress was unchanged.

Melatonin attenuates RV inflammation and apoptosis under adrenergic overload without preventing hypertrophy or markedly affecting lungs and skeletal muscle, supporting its potential as adjunctive therapy in cardiac diseases.