Rac1 inhibition protect against platelet induced organ injury in Diabetes Mellitus

Abstract

Background: Diabetes mellitus is one of the common causes for activation of platelet. Inflammation-induced abnormal platelet function contributes to chronic complications, which are consider the leading causes of death and morbidity among diabetics.

Objective: Rac1, a 21kD G-protein has been shown to regulate a variety of platelet functions; we predicted that Rac1 could regulate platelet release of CXCL4 and CCL5, which may leads to organ injury in Diabetes Mellitus.

Patients and Methods: Diabetes Mellitus' effect on Rac1 activation implicated in platelet activation, was investigated as platelet-induced inflammation and organ injuries. 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 and CCL5 were assayed using ELISA, and histology scores for kidney and pancreas was examined.

Results: Our results show that Diabetes Mellitus was induced in mice by streptozotocin. In addition, platelet chemokines (CXCL4, CCL5) were markedly higher in diabetic mice when compared to the sham group. Moreover, pretreatment of diabetic mice induced by STZ, with NSC23766 decreased kidney and pancreatic injuries assessed by histology score, P-value <0.05.

Conclusion: Our study reveals that Rac1 has a critical role in platelet chemokines secretion due to diabetes-induced inflammation in the kidneys and pancreas, and targeting Rac1 could be a target for innovative treatment to control inflammation in a diabetic individual. Targeting platelets involved in inflammatory pathways could be part of a strategy in order to control and manage diabetes consequences.