Author/Authors :
Sharifi, A.M Department of Pharmacology, School of Medicine, Endocrinology and Metabolism Research Center (EMRC), Dr Shariati Hospital, Tehran University of Medical Sciences , Akbarloo, N Department of Pharmacology, School of Medicine, Endocrinology and Metabolism Research Center (EMRC), Dr Shariati Hospital, Tehran University of Medical Sciences , Sasani, F Department of Pathology, Veterinary School, Tehran University, Tehran
Abstract :
Background: Nitric oxide (NO), a major chemical form of
endothelium-derived relaxing factor and an important regulator
of vascular tone, is released by endothelial cells. The role
of NO is not restricted to the vascular system, and it participates
in the regulation of renal hemodynamics and renal excretory
function. There are increasing evidences indicating
that the elevated levels of NO play a primary pathogenic role
in the glomerular injury and renal failure.
Objectives: We sought to investigate the renoprotective or
nephrotoxic effects of various doses of isosorbide dinitrate as
an exogenous model, and induction of cholestasis as an endogenous
model of NO overproduction on renal function and
structure.
Methods: Parameters such as plasma and urine p-nitrophenyl-
N-acetyl-β-D-glucosaminidase (NAG)-activity, urea and
creatinine levels were measured.
Results: Urea, creatinine and NAG-activity in rats treated by
different doses of isosorbide as well as in cholestasis induced
rats, were higher than control group. This elevation was significantly
pronounced at higher doses of isosorbide.
Conclusion: NO overproduction would be nephrotoxic due to
oxidizing products of NO, peroxynitrite anion (ONOO–),
formed by the reaction of NO and superoxide radical (O2
–).
