Pyrrolidine dithiocarbamate treatment prevents ethylene glycol-induced urolithiasis through inhibition of NF-kappaB and p38-MAPK signaling pathways in rat kidney.
The aim of this study was to evaluate the role of the inducible nitric oxide synthase (iNOS), selective nuclear factor-kappaB (NF-kappaB) and p38-mitogene-activated protein kinase (p38-MAPK) on oxalate-induced crystal deposition in renal tubules. The rats were divided into three groups; group 1; control group, group 2; ethylene glycol (EG) group, group 3; EG + pyrrolidine dithiocarbamate (PDTC) group. Rats were sacrified on 7, 15 and 45th days. The iNOS expression, p65/NF-kappaB and p38/MAPK activity, and oxidative stress markers were evaluated in the kidney. Crystal depositions were evident on day 7, mild and severe crystallization were observed on day 15 and 45 in EG group, respectively. There was limited or no crystal formation in the EG + PDTC group. While EG stimulates iNOS, p65/NF-kappaB and p38/MAPK activity in renal tubules, PDTC inhibited it. PDTC prevents crystal depositions in renal tubules by reducing oxidative stress, iNOS, NF-kappaB, and p38-MAPK expression.
Ilbey
Yusuf Ozlem
YO
Bezm-i Alem Valide Sultan Vakif Gureba Research and Education Hospital, Department of Urology, Istanbul, Turkey. ozlemyusufilbey@hotmail.com
Ozbek
Emin
E
Simşek
Abdulmuttalip
A
Cekmen
Mustafa
M
Somay
Adnan
A
Tasci
Ali Ihsan
AI
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D019855:Ethylene Glycol / Q000008:administration & dosage; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013859:Thiocarbamates / Q000494:pharmacology* / Q000627:therapeutic use*; D052878:Urolithiasis / Q000139:chemically induced / Q000517:prevention & control*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D000975:Antioxidants; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D048051:p38 Mitogen-Activated Protein Kinases; D019855:Ethylene Glycol