Animal experiment:

Mice[1]13-week-old C57BL/6J male mice are used throughout the study. After 1 week of acclimation, 15 mice are injected I.P. with streptozotocin (STZ) at a dosage of 55 mg/kg body weight daily for five consecutive days. Additional 15 mice as controls (Ctrl) are injected with a vehicle solution (0.1 mol/L citrate acid buffer, pH 4.3-4.5). Seven days after the last STZ administration, hyperglycemic mice (3-hour fasting blood glucose ≥250 mg/dL) are considered T1D (DM). This time point is defined as a baseline. Three months after diabetes induction, five diabetic and five control mice are sacrificed and blood and kidneys harvested. The remaining animals are divided in four groups: Normal control with vehicle (Ctrl), Normal control with Clopidogrel (Ctrl+ Clo), T1D (DM) with vehicle, and DM with Clopidogrel treatment (DM+Clo) and are treated with 20 mg/kg b.w./day Clopidogrel or with vehicle administered in their drinking water for three additional months. At the end of experiment, mice are intraperitoneally anesthetized with Avertin (tribromoethanol, 350 mg/kg) and sacrificed to collect blood and kidneys for mRNA, protein, and histological analyses[1].

Clopidogrel is a well-known and orally active platelet inhibitor that targets P2Y12 receptor. Clopidogrel is used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. P2Y12 receptor[1].

Clopidogrel, administered during the last three months, significantly decreases blood glucose, collagen and fibronectin expression compared to vehicle-treated diabetic mice. Clopidogrel markedly ameliorates hyperglycemia-induced renal fibrosis[1]. The combination therapy of clopidogrel and aspirin (dual-antiplatelet therapy) has been shown to be significantly beneficial compared to aspirin monotherapy and has also shown to decrease sub-acute stent thrombosis as well as recurrent ischemic events following ACS[2].

[1]. Zongyu Zheng, et al. Clopidogrel Reduces Fibronectin Accumulation and Improves Diabetes-Induced Renal Fibrosis. Int J Biol Sci. 2019 Jan. [2]. An insight into the interaction between clopidogrel and proton pump inhibitors By Shah, Bhavik S.; Parmar, Sanjay A.; Mahajan, Shailaja; Mehta, Anita A. From Current Drug Metabolism (2012), 13(2),225-235.