Hyperbaric oxygen treatment augments the efficacy of cilazapril and simvastatin regimens in an experimental nephrotic syndrome model.
BACKGROUND
Oxidative stress plays a role in the mechanism of chronic kidney disease (CKD), and antioxidant regimes are regarded as promising treatment modalities. We compared the effects of cilazapril, simvastatin, and hyperbaric oxygen (HBO) treatment on proteinuria and on oxidative stress in adriamycine (ADR)-induced proteinuria.


METHODS
Seventy male Sprague-Dawley rats were housed, and 60 were injected with ADR to induce nephrosis. After the stabilization of proteinuria, rats were treated for 6 weeks with simvastatin (n = 10, 4 mg/kg/day), cilazapril (n = 10, 10 mg/kg/day), HBO (n = 10, 2.8 athmosphere absolute, 90 min/daily), HBO + cilazapril (n = 10), HBO + simvastatin (n = 10), and vehicle (n = 10). After euthanization at 12 weeks, protein carbonyl (PCO), superoxide dismutase (SOD), and glutathion peroxidase (GPx) levels were analyzed from tissues. The histological alterations in the kidneys were determined by semiquantitative scoring.


RESULTS
Protein carbonyl (PCO) levels were higher (p < 0.001), and the GPx and SOD levels were lower (p < 0.001 for all) in the nephrotic rats. Proteinuria was correlated to PCO (r = 0.483), GPx (r = -0.686), or SOD (r = -0.620) (p < 0.001 for all). Superoxide dismutase (SOD) (beta = -0.381, p = 0.02) and GPx (beta = -0.509, p < 0.001) were independently related to proteinuria levels. Both cilazapril and simvastatin significantly improved GPx, SOD, PCO, and proteinuria. When HBO was combined with either drug, the above markers further improved (p < 0.001). Both regimens caused distinct histological features, while the combination of HBO made much significant histological improvement.


CONCLUSIONS
Both cilazapril and simvastatin regimens improve oxidative stress and proteinuria, while the effects significantly increase with the combination of HBO treatment. HBO seems to be a candidate antioxidant strategy in glomerular diseases.
Sonmez
Alper
A
Department of Internal Medicine, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Yilmaz
Mahmut Ilker
MI
Department of Nephrology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey. mahmutiyilmaz@yahoo.com.|Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, K 56 Karolinska University Hospital at Huddinge, 141 86, Huddinge, Stockholm, Sweden. mahmutiyilmaz@yahoo.com.
Korkmaz
Ahmet
A
Department of Physiology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Topal
Turgut
T
Department of Physiology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Caglar
Kayser
K
Department of Nephrology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Kaya
Ayper
A
Department of Pathology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Eyileten
Tayfun
T
Department of Nephrology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Yenicesu
Mujdat
M
Department of Nephrology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Oguz
Yusuf
Y
Department of Nephrology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Basal
Seref
S
Department of Urology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Ipcioglu
Osman Metin
OM
Department of Biochemistry, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
Vural
Abdulgaffar
A
Department of Nephrology, Gülhane School of Medicine, Etlik, 06018, Ankara, Turkey.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017315:Cilazapril / Q000494:pharmacology* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004317:Doxorubicin; D005979:Glutathione Peroxidase / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006931:Hyperbaric Oxygenation; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D011507:Proteinuria / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017315:Cilazapril; D004317:Doxorubicin; D019821:Simvastatin; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase