Combination of Captopril with Gliclazide Decreases Vascular and Renal Complications and Improves Glycemic Control in Rats with Streptozotocin- Induced Diabetes Mellitus

Abstract

Background: The common antihypertensive angiotensin-converting enzyme (ACE) inhibitor captopril was reported to possess antioxidant and anti-inflammatory effects in different experimental models, diabetic vascular complications arises from increased vascular endothelial inflammation and oxidative stress as well as decreased nitric oxide bioavailability in the vessel walls due to poor glycemic control. Objective: This study aimed to evaluate the role of captopril and gliclazide in decreasing diabetes mellitus (DM) vascular complications caused by decreased cellular glucose uptake and impaired endothelial nitric oxide metabolism, as well as examine the effect of combination on diabetic renal complication and plasma lipid profile. Materials and methods: Adult male Wister rats received captopril (25 mg/kg/day) and/or gliclazide (10 mg/kg/day) by oral gavage daily for one month after induction of DM using streptozotocin (50 mg/kg, i.p., once). Serum glucose and insulin levels, inflammatory mediatory like TNF-α, oxidative stress biomarkers like glutathione and nitric oxide, and plasma lipid profile were measured. Besides, histopathological examination of thoracic aorta and kidney tissues, while Western blot assessed the expression of nitric oxide synthase (NOS) subtypes in the thoracic aorta. Results: Captopril significantly improved vascular architecture and oxidative stress and modulated nitric oxide synthesis via regulation of nitric oxide synthases, as well as decreased inflammation via down-regulating TNF-α, decreased systolic and diastolic blood pressure and improved serum lipid profile in diabetic rats. Gliclazide increased serum insulin and decreased serum glucose, as well as its antioxidant and anti-inflammatory effects. Discussion and conclusions: Captopril showed a promising protective effect against DM vascular complications, at least via nitric oxide modulating effect, antioxidant effect and anti-inflammatory activity that appeared in biochemical and histopathological findings, lipid profile, renal function and architecture improvements. Combining gliclazide with captopril gives an additive effect through enhanced glycemic control and increased anti-oxidant and anti-inflammatory properties above captopril alone.

Co-Delivery of Dexamethasone and Captopril by α8 Integrin Antibodies Modified Liposome-PLGA Nanoparticle Hybrids for Targeted Anti-Inflammatory/Anti-Fibrosis Therapy of Glomerulonephritis

“…CAP is a synthetic angiotensin converting enzyme (ACE) inhibitor with antioxidant effect and can also effectively inhibit the formation of renal fibrosis and scarring by inhibiting the production of transforming growth factor-β (TGF-β). 23–25 In view of their action characteristics of, simultaneous targeted delivery of DXMS and CAP to the focal sites of GN is a meaningful strategy for achieving the regulation of ” inflammation/ fibrosis.”…”

The angiotensin-converting enzyme inhibitor, captopril, suppressed hepatic stellate cell activation via NF-kappaB or wnt3α/β-catenin pathway

“…Captopril is an inhibitor of angiotensin converting enzyme (ACE), which is commonly used to low blood pressure in patients with high blood pressure [6].…”

“…Captopril is an inhibitor of angiotensin converting enzyme (ACE), which is commonly used to low blood pressure in patients with high blood pressure [ 6 ]. Captopril combined with gliclazide has been found to reduce vascular and renal complications and control blood glucose in streptozotocin-induced diabetic rats [ 7 ].…”