Title:Combination of Captopril with Gliclazide Decreases Vascular and Renal Complications and Improves Glycemic Control in Rats with Streptozotocin- Induced Diabetes Mellitus
Volume: 21
Issue: 6
Author(s): Sayed M.M. Mizar*, Magy R. Kozman, Ali A. Abo-Saif and Basim A.S. Messiha
Affiliation:
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Fayoum University, Fayoum,Egypt
Keywords:
Nitric oxide synthase, anti-oxidant, streptozotocin, anti-inflammatory, hyperglycemia, lipid profile, renal function.
Abstract:
Background: The common antihypertensive angiotensin-converting enzyme (ACE) inhibitor
captopril was reported to possess anti-oxidant and anti-inflammatory effects in different experimental
models. Diabetic vascular complications arise 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 effects of the combination on diabetic renal
complication and plasma lipid profile.
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 mediators like TNF-α, oxidative stress
biomarkers like glutathione and nitric oxide, and plasma lipid profile were measured. Besides, histopathological
examination of the thoracic aorta and kidney tissues, 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 anti-oxidant and anti-inflammatory effects.
Conclusion: Captopril showed a promising protective effect against DM vascular complications, at
least via nitric oxide modulating effect, anti-oxidant 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.
