Inhibition of Rac 1 Protect Against Platelet Induced Liver and Kidney Injury in Diabetes Mellitus
Abstract
Diabetes mellitus both (Type 1 and Type 2) are one of the common causes for activation of platelet. Inflammation-induced abnormal platelet function contributes to chronic complications, which are the leading causes of death and morbidity among diabetics. Rac1 has been shown to regulate a variety of platelet functions; predicted Rac1could regulate platelet release of CXCL4, which leads to kidney injury in Diabetes Mellitus. Diabetes mellitus' effect on Rac1 activation, a 21kD G-protein implicated in platelet activation, was investigated and platelet induced inflammation and kidney injury. Swiss albino male mice were pretreated with 5 mg/kg of a specific Rac1 inhibitor NSC23766 and injected with (45 mg/kg body wt.) streptozotocin, twice for five days. Moreover, the concentration of serum chemokines CXCL4 were assayed using ELISA and histology score for kidney were examined. Our results showed that Diabetes mellitus was induced in mice by streptozotocin. In addition, platelet chemokines (CXCL4) were markedly higher in diabetic mice when compared to the sham (control) group. Moreover, pretreatment with NSC23766 decreased liver and kidney injury assessed by histology score, P-value <0.05. Our study reveals that Rac1 has a critical role in platelet chemokines secretion due to diabetes-induced inflammation in the liver and kidneys, targeting Rac1 could be a target for innovative treatment to control inflammation in diabetic individual. Targeting platelets involved in inflammatory pathways could be part of a strategy in order to control and manage diabetes and its consequences.
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