The effect of verapamil on the antioxidant defence system in diabetic kidney.
BACKGROUND
The aim of this study was to examine the effect of verapamil (VP) on lipid peroxidation and activities of key antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px); as well as on glomerular basement membrane (GBM) thickness in streptozotocin-induced diabetic kidney in rats.


METHODS
Wistar male rats were divided into three groups, 12 rats each: the control (C), diabetic rats (DR), and DR receiving VP, 7 mg/kg body weight in drinking water (DR + VP). Blood glucose (BG) and HbA(1c) levels, 24-h urinary albumin excretion (UAE) and body weight (BW) were measured every week (0-12 weeks). After 6 and 12 weeks, the animals were sacrificed and malondialdehyde (MDA) content and activities of SOD, CAT and GSH-Px were determined in the kidney homogenate supernatants. Electron micrographs of the glomeruli were scanned and morphometric investigations were performed by means of a computer image analysis system to compare the glomerular basement basal membrane (GBM) thickness.


RESULTS
The levels of BG, HbA(1c) and UAE in DR were significantly higher than in the C group. A progressive increase in the MDA level and a decrease in the SOD, CAT and GSH-Px activities in the kidney of DR were observed after 6 and 12 weeks. VP administration did not affect BW changes, BG and HbA(1c) levels in DR. VP decreased lipid peroxidation and augmented the activities of antioxidant enzymes studied in the kidneys of DR as well as decreased kidney weight, GBM thickness and albuminuria in DR.


CONCLUSIONS
These results confirm the role of oxidative stress in the development of diabetic nephropathy and point to the possible antioxidative mechanism of the nephroprotective action of VP.
Kedziora-Kornatowska
K
K
Department and Clinics of Geriatrics, L. Rydygier Medical University of Bydgoszcz, Bydgoszcz, Poland. kedzioraj@yahoo.com
Szram
S
S
Kornatowski
T
T
Szadujkis-Szadurski
L
L
Kedziora
J
J
Bartosz
G
G
D000419:Albuminuria / Q000652:urine; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology*
D000975:Antioxidants; D001786:Blood Glucose; D002374:Catalase; D005979:Glutathione Peroxidase; D006442:Glycated Hemoglobin; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D014700:Verapamil