Department of Clinical and Toxicological Analyses, Federal University of Rio Grande Do Norte (UFRN), Av. General Gustavo Cordeiro de Farias, S/N, Faculdade de Farmácia, Petrópolis, Natal, RN, CEP: 59012-570, Brazil.
Department of Pharmacy, Federal University of Rio Grande Do Norte (UFRN), Natal, RN, 59012-570, Brazil.
Sci Rep. 2020 Jul 21;10(1):12098. doi: 10.1038/s41598-020-69001-2.
Chloroquine (CQ) and hydroxychloroquine, are promising anti-inflammatory drugs for the treatment of Diabetes mellitus (DM) to prevent associated complications. Therefore, this study evaluated the anti-inflammatory effects of CQ-free and CQ-incorporated polylactic acid nanoparticles (NPs) in the peripheral blood mononuclear cells (PBMCs) of patients with type 1 Diabetes mellitus (T1DM). In total, 25 normoglycemic individuals and 25 patients with T1DM aged 10-16 years were selected and glycemic controls evaluated. After cell viability assessed by MTT assay, T1DM PBMCs were subjected to a CQ concentration of 10 µM in three different conditions: not treated (NT), treated with CQ, and treated with CQ NPs. The cells were incubated for 48 h, and the mRNA expressions of cytokines IL1B, IFNG, TNFA, IL12, and IL10 were determined by relative quantification through real-time PCR at 24 h intervals. IL1B expression decreased in CQ and CQ NP-treated cells after 48 h (p < 0.001) and 24 h (p < 0.05) of treatment, respectively. IFNG and IL12 expressions significantly decreased (p < 0.001) in cells treated with CQ and CQ NPs at 24 and 48 h compared to NT. TNFA and IL10 expressions significantly decreased after 48 h (p < 0.001) and 24 h (p < 0.002), respectively, by both CQ and CQ NPs treatment. Despite being a preliminary in vitro study, CQ has anti-inflammatory activity in the primary cells of T1DM patients and could represent an alternative and adjuvant anti-inflammatory therapy to prevent diabetes complications.
氯喹（CQ）和羟氯喹是治疗糖尿病（DM）以预防相关并发症的有前途的抗炎药物。因此，本研究评估了CQ 游离和 CQ 结合的聚乳酸纳米粒子（NPs）在 1 型糖尿病（T1DM）患者外周血单核细胞（PBMCs）中的抗炎作用。总共选择了 25 名血糖正常的个体和 25 名年龄在 10-16 岁的 T1DM 患者，并评估了血糖控制情况。通过 MTT 测定法评估细胞活力后，将 T1DM PBMC 置于三种不同条件下的 10 µM CQ 浓度下：未处理（NT）、用 CQ 处理和用 CQ NPs 处理。细胞孵育 48 小时后，通过实时 PCR 以 24 小时的间隔确定细胞因子 IL1B、IFNG、TNFA、IL12 和 IL10 的 mRNA 表达。在 48 小时（p < 0.001）和 24 小时（p < 0.05）处理后，CQ 和 CQ NP 处理的细胞中 IL1B 表达降低。CQ 和 CQ NPs 处理的细胞中 IFNG 和 IL12 表达在 24 和 48 小时时均显著降低（p < 0.001）。与 NT 相比，CQ 和 CQ NPs 处理的细胞在 48 小时（p < 0.001）和 24 小时（p < 0.002）时 TNFA 和 IL10 表达均显著降低。尽管这是一项初步的体外研究，但 CQ 在 T1DM 患者的原代细胞中具有抗炎活性，可能代表一种替代和辅助抗炎治疗方法，以预防糖尿病并发症。
