Efeito modulador in vitro de um complexo de inclusão resveratrol-metil-β-ciclodextrina sobre a inflamação e o estresse oxidativo induzidos pela hemina na doença falciforme.

Abstract

Introduction: Sickle cell disease (SCD) is a hemoglobinopathy characterized by the formation of hemoglobin S (HbS). When deoxygenated, HbS triggers polymerization, aggregation, and hemolysis, releasing products such as heme, which in turn initiate inflammatory processes and oxidative stress. Resveratrol (RES) is a polyphenol described as having anti-inflammatory and antioxidant properties in vitro, but with limited bioavailability. Cyclodextrins (CD) enable the formation of inclusion complexes with hydrophobic molecules like resveratrol, enhancing its bioavailability. Objective: To investigate the effect of a resveratrol–methyl-β-cyclodextrin (RES-MBCD) inclusion complex on hemin-induced oxidative and pro-inflammatory stress in THP-1 cells and peripheral blood mononuclear cells (PBMC) from SCD patients. Materials and Methods: Cells were pre-treated with RES-MBCD (5, 15, and 25 µM) prior to induction of stress with hemin (30 or 70 µM). RES-MBCD cytotoxicity, DPPH radical scavenging activity, reactive oxygen species (ROS) production, lipid peroxide levels, and the quantification of pro-inflammatory cytokines (TNF-α and IL-6) were assessed. Results: RES-MBCD did not exhibit significant cytotoxicity on THP-1 cells at 24 hours and showed lower cytotoxicity compared to free RES at 72 hours (p < 0.0001), along with greater DPPH radical scavenging capacity (p < 0,05). RES-MBCD reduced ROS production (p < 0.01) and TNF-α quantification (p < 0.05) induced by hemin in THP-1 cells. However, it increased TNF-α (p < 0.05) and IL-6 (p < 0,05) quantification in PBMC from SCD patients. Conclusion: These findings suggest that RES-MBCD exhibits remarkable antioxidant and immunomodulatory effects against hemin-induced stress, with lower cytotoxicity compared to free RES, highlighting the potential of resveratrol as a bioactive compound of therapeutic interest in SCD.