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

Author(s)

Teixeira-Fonseca, Jorge Lucas ; Belato y Orts, Diego Jose ; da Silva, Polyana Leal ; Conceicao, Michael Ramon de Lima ; Hermes, Hernan ; Prudencio, Carlos R. ; Roman-Campos, Danilo

• Document type: Journal article
• Source: Arquivos Brasileiros de Cardiologia; v. 121, n. 12, p. 11-pg., 2024-01-01.

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-beta, interleukin 6 and tumor necrosis factor-alpha) 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. (AU)

• FAPESP's process: 21/05584-7 - Assessment of acute and chronic toxicity of the heart and brain exposed to pesticides found in potable water in Brazil
• Grantee: Danilo Roman Campos
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 22/07256-0 - Role of SCN5A polymorphisms on pharmacological properties of pesticides against Nav1.5
• Grantee: Diego Jose Orts y Belato
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/14635-1 - Modeling of monogenic diseases for physiopathological studies and pharmacological tests using specialized cells derived from iPSCs
• Grantee: João Bosco Pesquero
• Support Opportunities: Research Projects - Thematic Grants