Chloroquine as a promising adjuvant therapy for type 1 Diabetes Mellitus

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. Diabetes mellitus (DM) is a serious health concern worldwide and patients with diabetes develop health problems due to complications, leading to the need for increased medical attention, a reduced quality of life, and premature death 1,2. According to the International Diabetes Federation, more than 463 million people had diabetes in 2019, which is projected to reach 700 million in 2045. Therefore, continuous medical monitoring is necessary to reduce the risk of complications 2. Type 1 DM (T1DM) occurs primarily in childhood with over 100,000 children and adolescents diagnosed each year. It is a chronic autoimmune disease characterized by hyperglycemia due to the destruction of pancreatic β cells, leading to an absolute deficiency of insulin 1,3. In the long run, inadequate glycemic control leads to the formation of advanced glycation end products (AGEs), which in turn cause changes to synthesis and damage to tissue structure and function. In addition, 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. Generally 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 membra...

Comparison of the Efficacy of Different Insulin Administration and Blood Glucose Monitoring Methods in the Treatment of Type 1 Diabetes Mellitus in Children

“…Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by T lymphocyte-mediated directed destruction of islet β cells, which leads to absolute insufficiency of insulin secretion and disorders of glucose, lipid, and protein metabolism [ 1 , 2 ]. Epidemiological studies have shown that the incidence of T1DM is increasing year-by-year globally, with a trend of younger age [ 3 ], and the annual growth rate of T1DM in children <5 years old is 3–4% [ 4 ].…”

The Critical Role of Aromatic-Aromatic Drug-Polymer Interactions to Provide Nanomedicines Containing Chloroquine: A Simple Proposal to Provide High Encapsulation, High Stability, and Prolonged Drug Release

“…In addition, several investigations indicates its potential administration in the treatment of another chronic diseases (i.e. cancer [10,11], diabetes [12,13], atherosclerosis [14], dermatomyositis [15], and Sjögren's syndrome [16], among others). Several factors have in uenced on the attention of CQ, highlighting their well-known immunomodulatory capacity [17].…”