Hyperbaric oxygen treatment augments the efficacy of a losartan regime in an experimental nephrotic syndrome model.
OBJECTIVE
Proteinuria is associated with oxidant stress and inflammation. Hyperbaric oxygen (HBO) treatment has anti-inflammatory and anti-oxidant effects. The aim of the study was to investigate the benefits of HBO treatment on an experimental nephrotic syndrome model.


METHODS
50 male Sprague-Dawley rats weighing 255 +/- 39 g were housed. Forty rats were injected 6 mg/kg adriamycin into tail veins under anesthesia to induce nephrosis, while 10 rats were spared as sham control. After the stabilization of proteinuria at the sixth week, the rats were treated for 6 weeks by losartan (n = 10, 30 mg/kg/day), HBO (n = 10, 2.8 atmosphere absolute, 90 min/day), HBO + losartan (n = 10) and vehicle (n = 10). Protein carbonyl (PCO), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were analyzed from tissue specimens. Biochemical markers were studied from venous samples and 24-hour urine was collected for proteinuria. The surviving animals at 12 weeks (vehicle group (n = 6), HBO (n = 6), losartan (n = 8), HBO + losartan (n = 10) were sacrificed. Glomerular sclerosis, tubulointerstitial and blood vessel changes were determined by semiquantitative scoring.


RESULTS
The PCO levels increased (p < 0.001), and the GPx and SOD levels decreased (p < 0.001 for both) in the nephrotic rats. In losartan and HBO groups GPx levels increased (p = 0.001, p = 0.002 respectively), but PCO and SOD levels did not change. The combination of HBO with losartan significantly increased the GPx and SOD levels (p = 0.001 for both) and decreased PCO levels (p = 0.005). HBO but not losartan significantly reduced proteinuria (p < 0.001). The combination of HBO and losartan reduced proteinuria better than the single losartan regime (p < 0.001). The effect of the combination was also noticed on the histological examination of the kidneys. The activities, appetites, weight gains, and improvement of edema were better in the HBO combined with losartan regime.


CONCLUSIONS
These results indicate that the addition of HBO therapy to a conventional regime, angiotensin receptor blockers, has significant benefits in the management of proteinuria. Future clinical studies are needed to elucidate the role of HBO and other antioxidant strategies in the treatment of proteinuria.
Yilmaz
Mahmut Ilker
MI
Department of Nephrology, Gulhane School of Medicine, Etlik-Ankara, Turkey. mahmutiyilmaz@yahoo.com
Korkmaz
Ahmet
A
Kaya
Ayper
A
Sonmez
Alper
A
Caglar
Kayser
K
Topal
Turgut
T
Eyileten
Tayfun
T
Yenicesu
Mujdat
M
Acikel
Cengizhan
C
Oter
Sukru
S
Yaman
Halil
H
Aktug
Huseyin
H
Oguz
Yusuf
Y
Vural
Abdulgaffar
A
Ikizler
T Alp
TA
D000818:Animals; D004317:Doxorubicin; D004357:Drug Synergism; D006931:Hyperbaric Oxygenation; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley
D004317:Doxorubicin; D019808:Losartan