The combination of zinc and glibenclamide limits cardiovascular complications in diabetic rats via multiple mechanisms.
Cardiovascular complications have become a major cause of mortality for diabetic patients. Glibenclamide is an effective hypoglycemic agent, but failed to alleviate diabetic complications. This study aimed to evaluate whether the addition of zinc to glibenclamide could mitigate such complications. Diabetes was induced using streptozotocin (60 mg/kg, i.p.). Cardiovascular complications were detected by the significant rise of cardiac enzymes, serum lipids, myocardial oxidative stress and cardiac levels of tumor necrosis factor-α (TNF-α, a marker for inflammation) as well as massive histological changes in the heart wall in diabetic control compared to non-diabetic group. Levels of serum nitric oxide and cardiac vascular endothelial growth factor (VEGF, an angiogenic marker) were lower in diabetic rats. Addition of zinc sulfate (30mg/kg) to glibenclamide (600βg/kg) resulted in significant improvement in cardiac biomarkers, oxidative status and serum lipids. Highly significant reduction in cardiac TNF-α (P<0.001), in addition to significant rise in nitric oxide (P< 0.05) and VEGF (P<0.01) were observed. Cellular infiltration and myocardial edema were ameliorated. These results suggest that a combined treatment of zinc and glibenclamide might be a potential therapy for preventing the risk of cardiovascular complications and reducing the mortality rate among diabetic patients.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia / Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Hala
H
Attia
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Nouf
N
Al-Rasheed
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Nawal
N
Al-Rasheed
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Laila
L
Faddah
D000818:Animals; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D048909:Diabetes Complications / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005905:Glyburide / Q000008:administration & dosage*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D019287:Zinc Sulfate / Q000008:administration & dosage*
D007004:Hypoglycemic Agents; D008055:Lipids; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D013311:Streptozocin; D019287:Zinc Sulfate; D005905:Glyburide