The potential anti-inflammatory effect of tetrahydrobiopterin administration in renal mass reduction-induced chronic renal failure in rats.
OBJECTIVE
To investigate the impact of tetrahydrobiopterin (BH4) supplementation on the markers of inflammation, and on the histological picture of the kidney in chronic renal failure C-reactive protein (CRF) induced in rats by subtotal nephrectomy (SNx).


METHODS
This study was performed at the Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia during the period from December 2005 to January 2007. Chronic renal failure was induced by 5/6 SNx in 20 male Wister rats, and another 10 rats were sham operated by flank incision and served as controls. Ten SNx rats received 10mg kg-1 BH4 intraperitoneally daily for 4 weeks. Plasma C-reactive protein (CRP), interlukin-6 (IL-6), malondialdehyde (MDA), and kidney functions were measured in all rats. Histopathological examination of the kidney tissues was also performed.


RESULTS
Untreated CRF rats showed significant elevation of plasma CRP, IL-6, and MDA levels, and significant decrease in plasma albumin and total protein levels, tubuloglomerular fibrosis and, interstitial tubular infiltration with inflammatory cells in comparison with the sham-operated rats. Tetrahydrobiopterin treatment decreased CRP, IL-6, and MDA levels, and decreased tubuloglomerular fibrosis and interstitial inflammation in treated CRF rats.


CONCLUSIONS
Supplementation with exogenous BH4 decreased markers of inflammation and protected the kidney against post-renal mass reduction histologic damage. Restoration of intracellular BH4 balance could normalize nitrous oxide production. Therefore, BH4 might be a promising strategy in attenuating inflammation in CRF. This may decrease endothelial dysfunction and limit the associated cardiovascular morbidity and mortality of this disease.
Korish
Aida A
AA
Department of Physiology, Faculty of Medicine, King Saud University, PO Box 2925, Riyadh 11461, Kingdom of Saudi Arabia. iaidakorish@hotmail.com
Arafah
Maha M
MM
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D002097:C-Reactive Protein / Q000378:metabolism*; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000209:etiology / Q000473:pathology*; D007677:Kidney Function Tests; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar
D015850:Interleukin-6; D001708:Biopterins; D008315:Malondialdehyde; D002097:C-Reactive Protein; C003402:sapropterin