Rapid communication: protective effect of a nuclear factor kappaB inhibitor, pyrolidium dithiocarbamate, in the kidney of rats with nephrolithiasis induced by ethylene glycol.
OBJECTIVE
To study the protective effects of a selective nuclear factor kappa B (NF-kappaB) inhibitor, pyrolidium dithiocarbamate (PDTC), on ethylene glycol-induced crystal deposition in the renal tubules, renal toxicity, as well as inducible nitric oxide synthase (iNOS) and NF-kappaB activities in rat kidneys.


METHODS
Rats were divided into three equal groups: control, ethylene glycol-treated (EG), and ethylene glycol + PDTC treated (EG+PDTC). Rats were sacrificed on day 7, 15, or 45, and tissue sections were evaluated under light and transmission electron microscopy for the presence and degree of crystal deposition and toxicity in the kidneys. The iNOS and NF-kappaB activity were evaluated immunohistochemically, with p65 being stained to define NF-kappaB activity. Crude extracts of the cortex were used to determine reduced glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) concentrations.


RESULTS
Crystal depositions were more evident in the proximal tubules on day 7 in the EG than in the other groups. Mild crystallization was observed on day 15, and severe crystallization and granulovacuolar epithelial-cell degeneration were observed on day 45. There was limited or no crystal formation in the EG+PDTC group and completely normal renal and tubular structures in the control group. Whereas ethylene glycol administration stimulated iNOS and NF-kappaB/p65 activity in renal tubules, PDTC inhibited it. Rats given only vehicle demonstrated no significant alterations. Hyperoxaluria, a marked increase in MDA and NO concentrations, and a decrease in GSH were observed in the EG group.


CONCLUSIONS
This experiment has shown the role of transcription factors, NF-kappaB, and iNOS in ethylene glycol-induced crystal depositions in renal tubules.
Tugcu
Volkan
V
Department of Urology, Bakirkoy Research and Training Hospital, Istanbul, Turkey. volkantugcu@yahoo.com
Ozbek
Emin
E
Kemahli
Eray
E
Cekmen
Mustafa Baki
MB
Caner
Nazli
N
Somay
Adnan
A
Erturkuner
Pelin
P
Seckin
Ismail
I
Demir
Cennet Gural
CG
Altug
Tuncay
T
Tasci
Ali Ihsan
AI
D000818:Animals; D003460:Crystallization; D019855:Ethylene Glycol / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000187:drug effects*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D053040:Nephrolithiasis / Q000209:etiology* / Q000628:therapy; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology*
D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D009569:Nitric Oxide; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D019855:Ethylene Glycol; D005978:Glutathione