Effect of Combination of Angiotensin-Converting Enzyme Inhibitors and Vitamin D Receptor Activators on Cardiac Oxidative Stress in Diabetic Rats

Tarek Mohamed Ali; Osama Mahmoud Mehanna; Amgad Gaber Elsaid; Ahmad El Askary

doi:10.1016/j.amjms.2016.04.016

Effect of Combination of Angiotensin-Converting Enzyme Inhibitors and Vitamin D Receptor Activators on Cardiac Oxidative Stress in Diabetic Rats

Am J Med Sci. 2016 Aug;352(2):208-14. doi: 10.1016/j.amjms.2016.04.016. Epub 2016 Apr 22.

Authors

Tarek Mohamed Ali¹, Osama Mahmoud Mehanna², Amgad Gaber Elsaid³, Ahmad El Askary⁴

Affiliations

¹ Department of Medical Laboratory Science, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia; Department of Medical Physiology, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt. Electronic address: tarek70ali@gmail.com.
² Department of Medical Physiology, Faculty of Medicine, Taif University, Taif, Saudi Arabia; Department of Medical Physiology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
³ College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia; Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
⁴ Department of Medical Laboratory Science, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia; Department of Medical Biochemistry, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

PMID: 27524220
DOI: 10.1016/j.amjms.2016.04.016

Abstract

Background: The principle mediator of diabetic myocardial injury is oxidative stress. The aim was to compare the effect of monotherapy with enalapril, angiotensin-converting enzyme inhibitor and paricalcitol (vitamin D receptor activator), to the combined therapy with both drugs on the cardiac oxidant-antioxidant balance in the type 2 diabetic rats.

Materials and methods: A total of 50 male Sprague-Dawley rats were divided into 5 groups, namely the normal control and diabetic, vehicle, enalapril, paricalcitol and paricalcitol and enalapril-treated groups. Enalapril was given at a dose of (25mg/L) in drinking water once daily and paricalcitol was given intraperitoneally (0.8μg/kg/3 × week) for 3 months. Glycemic status, cardiac oxidant-antioxidant parameters and histologic examination were determined.

Results: Paricalcitol and combined treatment significantly (P < 0.01) reduced the level of fasting, postprandial blood glucose, homeostatic model assessment-insulin resistance, cardiac malondialdehyde and nitric oxide. Moreover, they significantly (P < 0.01) increased the levels of insulin and c-peptide compared to diabetic control rats. Combined treatment significantly (P < 0.01) raised the level of glutathione, glutathione S-transferase and catalase more than monotherapy.

Conclusion: The combination of angiotensin-converting enzyme inhibitors and vitamin D receptor activators has a superior effect on reducing cardiac oxidative stress by raising antioxidant activity than monotherapy in diabetic rats.

Keywords: Diabetes; Enalapril; Oxidative stress; Paricalcitol; Streptozotocin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme Inhibitors / administration & dosage*
Animals
Diabetes Mellitus, Experimental / drug therapy
Diabetes Mellitus, Experimental / metabolism*
Diabetes Mellitus, Experimental / pathology
Drug Therapy, Combination
Enalapril / administration & dosage*
Ergocalciferols / administration & dosage*
Male
Oxidative Stress / drug effects*
Oxidative Stress / physiology
Rats
Rats, Sprague-Dawley
Receptors, Calcitriol / agonists
Receptors, Calcitriol / metabolism*
Treatment Outcome

Substances

Angiotensin-Converting Enzyme Inhibitors
Ergocalciferols
Receptors, Calcitriol
paricalcitol
Enalapril