Razi Institute for Drug Research (RIDR) of Iran University of Medical Sciences and Health Services (IUMS)
Abstract
Diabetic nephropathy (DNP) is considered a CRD (Chronic Renal Disease);
it is a major cause of illness and premature death in people with DM.
The present study was designed to illustrate the role of CCBs
(amlodipine and diltiazem) in prevention and treatment of DNP in rats.
Eighty male albino rats weighing (130-180gm) were used in this study.
These animals were subdivided into five equal groups. Insulinopenic
diabetes was induced by STZ, two weeks later, 30 minutes of complete
ischemia was induced in the left kidney to induce diabetic nephropathy
then treatment was started for 12 weeks. At the end of experiment urine
samples and blood samples were taken for biochemical analysis and
kidneys were taken for histopathological evaluation. Combination of
renal ischemia with DM produced a significant increase in rat weight,
rat kidney weight, BUN (Blood Urea Nitrogen) level, K/B (Kidney/Body
weight) ratio, random blood glucose, 24 hrs urine proteins, and 24 hrs
urine volumes and creatinine clearance. Treatment with diltiazem or
amlodipine significantly lowered elevated SBP and elevated 24 hrs urine
volumes. Furthermore, treatment with captopril produced a highly
significant lowering of elevated SBP and elevated serum creatinine; and
a significant reduction in elevated K/B ratio and proteinuria. Light
microscopic examination of diabetic kidneys revealed glomerulopathy
characterized by thickening of the glomerular basement membrane,
mesangial matrix expansion, arteriolar hyalinosis and large
proteinaceous deposits occluding some capillary loops and hyaline
droplets within the glomeruli. Moreover, examination of kidneys of
ischemic animals by light microscope revealed focal tubular necrosis at
multiple points along the nephron, interstitial edema and accumulation
of leucocytes within dilated vasa recta
