Affiliation:
1. Núcleo de Pós-Graduação e Pesquisa, Hospital Santa Casa de Belo Horizonte, Rua Domingos Vieira 590, Santa Efigênia, 30150-240, Belo Horizonte, MG, Brazil
Abstract
Background:
Atorvastatin (ATV) inhibits the conversion of 3-Hydroxy-3-Methylglutaryl
Coenzyme A (HMG-CoA) to mevalonate formation and promotes lowering of the LDL cholesterol
fraction. However, ATV exhibits pleiotropic metabolic actions beyond cholesterol-lowering properties.
Objective:
We aimed to evaluate the effect of ATV on oxidizing species generation and cytokine secretion
in Peripheral Blood Mononuclear Cells (PBMNC) of Type 2 Diabetes Mellitus (T2DM) patients
in comparison to healthy control.
Methods:
Both NADPH-oxidase-dependent and mitochondrial ROS generation were assessed by
chemoluminescence luminol-dependent assay and fluorometric experiment, using Dichlorofluorescein
Assay (DCFH-DA), respectively. IL-1β and IL-6 were quantified by classical ELISA.
Results:
ATV inhibited NADPH-oxidase dependent ROS generation, but showed no effect on mitochondrial
ROS generation and activated IL-1β and IL-6 secretions in PBMNC from control and T2DM
patients. ROS generation and cytokine secretion in the presence of an inhibitor of Protein Kinase Cβ
(iPKCβ) and ATV led to similar results. The secretion of IL-1β, PDB-induced in the presence of
iPKCβ, but not ATV, was increased. ATV and iPKCβ exacerbated PDB-induced IL-6 secretion. LPS
activated the secretion of IL-1β and IL-6 which was potentiated by ATV.
Conclusion:
ATV inhibited ROS generation and activated IL-1 β/IL-6 secretion in PBMNC of diabetes
patients. Its effect was not affected by the hyperglymemia.
Funder
Foundation for Research Support of the State of Minas Gerais
Publisher
Bentham Science Publishers Ltd.
Subject
Immunology and Allergy,Endocrinology, Diabetes and Metabolism
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