Abstract
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.
Highlights
Chloroquine (CQ) and hydroxychloroquine, are promising anti-inflammatory drugs for the treatment of Diabetes mellitus (DM) to prevent associated complications
This demonstrated that type 1 Diabetes mellitus (T1DM) patients have values above those that are recommended by the American Diabetes Association (ADA) for good glycemic c ontrol[1]
There was no significant difference in the viability of peripheral blood mononuclear cells (PBMCs) of the NG and T1DM groups treated with CQ or CQ NPs after 24 (Fig. 1A,C) and 48 h (Fig. 1B,D) of treatment
Summary
Chloroquine (CQ) and hydroxychloroquine, are promising anti-inflammatory drugs for the treatment of Diabetes mellitus (DM) to prevent associated complications. AGEs activate the signaling cascade that causes an intense inflammatory response with the production of reactive oxygen species in nerve and endothelial cells, causing microvascular (nephropathy, neuropathy, and retinopathy) and macrovascular (coronary disease, cerebrovascular disease, and peripheral arterial disease) lesions[4,5]. Speaking, this event occurs when damage-associated molecular pattern proteins, AGEs, high mobility group box-1 proteins, heat shock proteins, and growth-specific protein 6 bind to toll-like receptors (TLRs) 2 and 4 on the β-cell membrane. Transcription of pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-8, IL-10, IL-12, and IFN-α, which, with the recruitment of CD4 + and CD8 + T cells and macrophages, leads to an intense inflammatory infiltrate in the pancreatic islets[6,7]
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