Natural flavonoids such as quercetin, (+)catechin and rutin as well as four methoxylated derivatives of quercetin used as models were investigated to elucidate their impact on the oxidant and antioxidant status of human red blood cells (RBCs). The impact of these compounds against metal toxicity was studied as well as their antiradical activities with DPPH assay. Antihemolytic experiments were conducted on quercetin, (+)catechin and rutin with excess of Fe, Cu and Zn (400 μM), and the oxidant (malondialdehyde, carbonyl proteins) and antioxidant (reduced glutathione, catalase activity) markers were evaluated. The results showed that Fe and Zn have the highest prooxidant effect (37 and 33% of hemolysis, respectively). Quercetin, rutin and (+)catechin exhibited strong antioxidant properties toward Fe, but this effect was decreased with respect to Zn ions. However, the Cu showed a weak antioxidant effect at the highest flavonoid concentration (200 μM), while a prooxidant effect was observed at the lowest flavonoid concentration (100 μM). These results are in agreement with the physico-chemical and antiradical data which demonstrated that binding of the metal ions (for FeNTA: (+)Catechin, K_LFeNTA = 1.6(1) × 10⁶ M^-1 > Rutin, K_LFeNTA = 2.0(9) × 10⁵ M^-1 > Quercetin, K_LFeNTA = 1.0(7) × 10⁵ M^-1 > Q35OH, K_LFeNTA = 6.3(8.7) × 10⁴ M^-1 > Quercetin3’4’OH and Quercetin 3OH, K_LFeNTA ~ 2 × 10⁴ M^-1) reflects the (anti)oxidant status of the RBCs. This study reveals that flavonoids have both prooxidant and antioxidant activity depending on the nature and concentration of the flavonoids and metal ions.

With diabetes being the 7th leading cause of death worldwide, overcoming issues limiting the oral administration of insulin is of global significance. The development of imine-linked-covalent organic framework (nCOF) nanoparticles for oral insulin delivery to overcome these delivery barriers is herein reported. A gastro-resistant nCOF was prepared from layered nanosheets with insulin loaded between the nanosheet layers. The insulin-loaded nCOF exhibited insulin protection in digestive fluids in vitro as well as glucose-responsive release, and this hyperglycemia-induced release was confirmed in vivo in diabetic rats without noticeable toxic effects. This is strong evidence that nCOF-based oral insulin delivery systems could replace traditional subcutaneous injections easing insulin therapy.

Children’s diabetes is represented by the Type 1 diabetes mellitus (T1DM). In T1DM, the persistence of hyperglycemia has been reported to cause increased production of oxygen free radicals through glucose autooxidation and nonenzymatic glycation. The aim of this study was to evaluate markers of oxidant/antioxidant status in diabetic children of Western Algeria. This study included 40 children with T1DM with mean age of 7.5 ± 1.7 years and 40 healthy age and sex matched controls. They were subjected to assessment of indicative parameters of lipoperoxidation, protein oxidation, changes in the status of antioxidant defense systems, plasma oxygen radical absorbance capacity (ORAC), glycated hemoglobin (HbA1c), total cholesterol and triglycerides. Malondialdehyde (MDA) and carbonyl proteins levels in plasma were significantly higher (4.03 ± 0.39 versus 2.53 ± 0.4 µmol/L, 5.03 ± 0.57 versus 3 ± 0.38 nmol/mg protein, respectively; P < 0.001) and a significant reduction in plasma total antioxidant capacity and vitamin C was observed in diabetic children than the controls (1.55 ± 0.28 versus 2.5 ± 0.23 AU, 37.58 ± 5.76 versus 48.8 ± 4.47 µmol/L, respectively; P < 0.001). Erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities were significantly higher (520 ± 40.42 versus 392.7 ± 42.66 U/g hemoglobin, 71.08 ± 5.18 versus 56.6 ± 2.84 U/g hemoglobin, respectively; P < 0.001), whereas erythrocyte glutathione reductase (GSH) reduced significantly (34.98 ± 2.34 versus 42.68 ± 3.03 U/g hemoglobin, respectively; P < 0.001) in diabetic children than the control subject. The present finding suggested that young diabetic patients were susceptible to oxidative stress. Appropriate support for enhancing antioxidant supply in these patients may help prevent complications due to oxidative injury. Key words: Children, oxidative stress, Type 1 diabetes mellitus.

Complications associated with Type 1 diabetes (T1D) have complex origins that revolve around chronic hyperglycemia; these complications involve hemostasis disorders, coagulopathies, and vascular damage. Our study aims to develop innovative approaches to minimize these complications and to compare the outcomes of the new approach with those of traditional methods. To achieve our objective, we designed novel nanoparticles comprising covalent organic frameworks (nCOF) loaded with insulin, termed nCOF/Insulin, and compared it to subcutaneous insulin to elucidate the influence of insulin delivery methods on various parameters, including bleeding time, coagulation factors, platelet counts, cortisol plasma levels, lipid profiles, and oxidative stress parameters. Traditional subcutaneous insulin injections exacerbated hemostasis disorder and vascular injuries in streptozotocin (STZ)-induced diabetic rats through increasing plasma triglycerides and lipid peroxidation. Conversely, oral delivery of nCOF/Insulin ameliorated hemostatic disorders and restored the endothelial oxidant/antioxidant balance by reducing lipid peroxidation and enhancing the lipid profile. Our study pioneers the understanding of how STZ-induced diabetes disrupts bleeding time, induces a hypercoagulable state, and causes vascular damage through lipid peroxidation. Additionally, it provides the first evidence for the involvement of subcutaneous insulin treatment in exacerbating vascular and hemostasis disorders in type 1 diabetes (T1D). Introducing an innovative oral insulin delivery via the nCOF approach represents a potential paradigm shift in diabetes management and patient care and promises to improve treatment strategies for type 1 Diabetes.