Reichert Cadiele Oliana, de Macedo Carolina Garcia, Levy Débora, Sini Bruno Carnevale, Monteiro Andréia Moreira, Gidlund Magnus, Maselli Luciana Morganti Ferreira, Gualandro Sandra Fátima Menosi, Bydlowski Sérgio Paulo
Lipids, Oxidation, and Cell Biology Group, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, 05403-900 Sao Paulo, Brazil.
Department of Immunology, Institute of Biomedical Sciences, Universidade de Sao Paulo, 05508-000 Sao Paulo, Brazil.
Antioxidants (Basel). 2019 Jul 30;8(8):252. doi: 10.3390/antiox8080252.
(1) Background: Oxidative stress, chronic inflammation, vasoocclusion, and free iron are all features present in sickle cell disease. Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action. Here, for the first time, we described PON-1 activities and PON-1, PON-2, PON-3 polymorphisms in patients with sickle cell disease, homozygous for HbSS, compared with healthy controls. (2) Methods: The groups were matched for age and gender. PON-1 activities (arylesterase and paraoxonase) were determined by enzymatic hydrolysis of phenylcetate and paraoxon, respectively. Polymorphisms were determined by Restriction Fragment Length Polymorphism- Polymerase Chain Reaction (RFLP-PCR). (3) Results: Plasma cholesterol and fractions, ApoA1 and ApoB levels were all decreased in sickle cell disease patients, while anti-oxidized low-density lipoprotein (LDL) antibodies and C-reactive protein were increased. Serum arylesterase activity was lower in sickle cell disease patients when compared with healthy controls. In patients, paraoxonase activity was higher in those with PON-1 RR Q192R polymorphism. In these patients, the increase of serum iron and ferritin levels and transferrin saturation were less pronounced than those observed in patients with QQ or QR polymorphism. No differences were observed with PON-1 L55M, and PON-2 and PON-3 polymorphisms. Multivariate regression analysis showed that transferrin and ferritin concentrations correlated with arylesterase and paraoxonase activities. (4) Conclusions: Both transferrin and ferritin were the main predictors of decreased arylesterase and paraoxonase activities in patients with sickle cell disease. LDL oxidation increased, and RR PON-1 Q192R polymorphism is likely to be a protective factor against oxidative damage in these patients.
(1) 背景：氧化应激、慢性炎症、血管阻塞和游离铁都是镰状细胞病的特征。对氧磷酶（PON）是具有抗炎作用的抗氧化酶家族（PON-1、PON-2、PON-3）。在此，我们首次描述了与健康对照相比，纯合子HbSS镰状细胞病患者的PON-1活性以及PON-1、PON-2、PON-3多态性。(2) 方法：两组在年龄和性别上相匹配。分别通过苯乙酸酯和对氧磷的酶促水解来测定PON-1活性（芳基酯酶和对氧磷酶）。通过限制性片段长度多态性-聚合酶链反应（RFLP-PCR）来测定多态性。(3) 结果：镰状细胞病患者的血浆胆固醇及其组分、载脂蛋白A1和载脂蛋白B水平均降低，而抗氧化低密度脂蛋白（LDL）抗体和C反应蛋白升高。与健康对照相比，镰状细胞病患者的血清芳基酯酶活性较低。在患者中，具有PON-1 RR Q192R多态性的患者对氧磷酶活性较高。在这些患者中，血清铁、铁蛋白水平的升高以及转铁蛋白饱和度的升高不如具有QQ或QR多态性的患者明显。在PON-1 L55M以及PON-2和PON-3多态性方面未观察到差异。多变量回归分析表明，转铁蛋白和铁蛋白浓度与芳基酯酶和对氧磷酶活性相关。(4) 结论：转铁蛋白和铁蛋白都是镰状细胞病患者芳基酯酶和对氧磷酶活性降低的主要预测指标。LDL氧化增加，并且RR PON-1 Q192R多态性可能是这些患者对抗氧化损伤的保护因素。
