Increase by NO synthase inhibitor of lead-induced release of N-acetyl-beta-D-glucosaminidase from perfused rat kidney.
Urinary N-acetyl-beta-D-glucosaminidase (NAG) had been shown to be a useful early marker of renal injury such as lead nephrotoxicity. This study investigated the effect of lead acetate on nephrotoxicity and its correlation with the nitric oxide (NO) system by determining the NAG release in perfused rat kidney. Lead acetate caused a time and concentration-dependent increase in enzymuria. The effect of concurrent perfusion with lead and L-arginine (L-arg) or L-N(G)-nitro arginine methyl ester (L-NAME) [substrate and inhibitor of NO synthase respectively] in the perfusion fluid was also studied by measuring NAG activity in the perfusate kidney rat. L-arg (2 mM) has significantly decreased the lead-induced NAG release (P < 0.001), and L-NAME (0.1 mM) has significantly increased the lead-induced enzyme release in a time-dependent manner (P < 0.001). Moreover, histological studies using light microscope showed that some of the epithelial cells of the proximal convoluted tubules are degenerated or necrotic and desquamated into the lumens in rat treated with lead acetate. This change occurs at 50 microg/dl of lead acetate and was increased by addition of L-NAME to lead acetate. However, addition of L-arg had no effect on histology of lead nephrotoxicity. This may suggest that lead may interfere with the NO system in rat kidney.
Dehpour
A R
AR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
Essalat
M
M
Ala
S
S
Ghazi-Khansari
M
M
Ghafourifar
P
P
D000118:Acetylglucosaminidase / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007854:Lead / Q000633:toxicity*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007854:Lead; D001120:Arginine; D019001:Nitric Oxide Synthase; D000118:Acetylglucosaminidase; D019331:NG-Nitroarginine Methyl Ester