In Vivo Anti-Inflammatory Activity of D-Limonene in a Rat Model of Monocrotaline-Induced Pulmonary Hypertension: Implications to the Heart Function

Abstract

Background: D-limonene (D-L) is the major monocyclic monoterpene in citrus plants with anti-inflammatory properties. Pulmonary hypertension (PH) can cause right heart dysfunction and increases the risk of death, partially due to inflammatory response in the heart. Objective: To evaluate the possible protective effect of D-L on cardiac function in a rat model of monocrotaline-induced PH (MCT-PH). Methods: Electrocardiogram was monitored in vivo. Masson Trichrome technique was deployed to verify fibrosis in the heart. Contractility function of isolated atrial tissue was studied using organ bath chamber. Real-time quantitative PCR was applied to quantify inflammation in the right ventricle. Results: The MCT-PH group showed electrical and structural heart remodeling, with the presence of fibrosis in the cardiac tissue and in vivo electrocardiographic changes. Treatment with D-L partially prevented the development of tissue fibrosis and the increase in P wave duration in the MCT-PH group. The contraction and relaxation velocity of isolated right and left atrium were accelerated in CTR and MCT-PH animals treated with D-L. Finally, D-L was able to prevent the abnormal expression of the key inflammatory cytokines (interleukin 1-β, interleukin 6 and tumor necrosis factor-α) in the right ventricle of MCT-PH animals. D-L was able to enhance the production of the anti-inflammatory cytokine Interleukin-10. Conclusion: Our results showed that in vivo administration of D-L partially prevented the molecular, structural and functional remodeling of the heart in the MCT-PH model with attenuation of the inflammatory response in the heart.