Nitric oxide regulates expression of sonic hedgehog and hypoxia-inducible factor-1alpha in an experimental model of kidney ischemia-reperfusion.
This study was designed to determine the effect of L-arginine on hypoxia inducible factor alpha (HIF-1 alpha) and Sonic hedgehog (Shh) levels considered to be involved in the development of ischemia/reperfusion (I/R) injury. Unilaterally nephrectomized Sprague-Dawley rats were subjected to 60 minutes of left renal ischemia followed by 45 minutes of reperfusion. Group 1 were sham-operated animals; group 2, I-R/Untreated animals; and group 3, I-R/L-Arg-treated animals. Serum creatinine, blood urea nitrogen (BUN), and kidney malondialdehyde (MDA) levels were determined as well as examining the kidneys histologically. The treatment of rats with L-Arg produced a significant reduction in the levels of BUN, creatinine, MDA, and histopathological score compared to renal I/R groups. The Shh expression in the tubulus epithelia were intensely increased in the I-R/L-Arg group when compared to that of the Sham-control and the I-R/untreated groups. Additionally, the HIF-1alpha expression in the tubulus epithelia and the interstitial spaces were intensely increased in the I-R/L-Arg group. These findings suggest that NO reduces the renal dysfunction associated with I/R of the kidney and may act as a trigger to induce Shh and HIF-1 activity.
Ozturk
Hayrettin
H
Abanty Izzet Baysal University, Medical School, Departments of Pediatric Surgery, Bolu, Turkey. hozturkmd@yahoo.com
Tuncer
Mehmet Cudi
MC
Ozturk
Hulya
H
Buyukbayram
Hüseyin
H
D000818:Animals; D001120:Arginine / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D053823:Hedgehog Proteins / Q000096:biosynthesis*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D053823:Hedgehog Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009569:Nitric Oxide; D008315:Malondialdehyde; D001120:Arginine; D003404:Creatinine