Diabetes mellitus (DM) is a prevalent cause of platelet (PLT) activation. Inflammation-induced dysregulated PLT function adds to chronic problems. Ras-related C3 botulinum toxin substrate 1 (Rac1), a 21 kDa G-protein, has been shown to modulate many PLT activities; we hypothesized that Rac1 may influence the PLT release of CXCL4 and CCL5, contributing to macrovascular and microvascular problems in DM. The study included Swiss albino male mice pretreated with the Rac1 inhibitor NSC23766 and streptozotocin (STZ) to induce diabetes. A sample of 150 diabetic patients and 50 healthy controls was also analyzed. Statistical analyses were performed using Mann-Whitney tests One hundred fifty confirmed diabetic patients which they visit Layla Qasim health center for diabetes and 50 healthy individuals were included in this study. The serum CXCL4 and CCL5 in diabetic patients and healthy volunteer were measured. Swiss albino male mice were given a pretreatment of 5 mg/kg of the Rac1 inhibitor NSC23766 and then injected with streptozotocin at a dosage of 45 mg/kg body weight, twice daily for five days. Rac1 activity in the PLT was measured using pulldown assay and western blot method. Blood chemokine concentrations were also assessed using ELISA, and histological scores for the kidney, liver, pancreas, and lung were evaluated. CXCL4 and CCL5 levels were markedly elevated in DM patients relative to healthy persons. Our findings indicated that streptozotocin developed diabetes mellitus in mice. GTP-Rac1 was induced in diabetic mice and pretreatment with NSC23766 was significantly lower compared to vehicle group. Furthermore, compared to the sham group, diabetic mice had significantly greater levels of CXCL4 and CCL5 (P < 0.05). CXCL4 levels were reduced by 80% following Rac1 inhibition (P < 0.05), while CCL5 levels decreased by 55.5% (P < 0.05). The current research indicates that Rac1 plays a pivotal role in releasing PLT chemokines due to diabetes-induced inflammation in several organs, and inhibiting Rac1 may represent a novel therapeutic approach to managing inflammation in diabetic individuals. |
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