Skip to main content
Erschienen in: International Urology and Nephrology 4/2009

01.12.2009 | Urology - Original Paper

Effects of apocynin and losartan treatment on renal oxidative stress in a rat model of calcium oxalate nephrolithiasis

verfasst von: Cheng-yang Li, Yao-liang Deng, Bing-hua Sun

Erschienen in: International Urology and Nephrology | Ausgabe 4/2009

Einloggen, um Zugang zu erhalten

Abstract

Background

Tissue culture studies found that renal epithelial cells suffer oxidative injury on exposure to high levels of oxalate (Ox) and calcium oxalate (CaOx) crystals; nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a major source of reactive oxygen species (ROS) production in kidney, has been shown to be involved in this event. The present study aimed to investigate whether this in vitro feature of NADPH oxidase could be confirmed in vivo.

Methods

Animal model of nephrolithiasis was established in adult male Sprague-Dawley rats by administration of 0.8% ethylene glycol (EG) in drinking water for 4 weeks. Simultaneous treatment with apocynin (0.2 g kg−1 day−1) or losartan (30 mg kg−1 day−1) by intragastric administration was performed in rats. At the end of the study, urinary 8-IP, a product of lipid peroxidation, and enzymatic activity of superoxide dismutase (SOD) in kidney homogenates were assessed as markers for state of renal oxidative stress (OS). Expression of NADPH oxidase subunit p47phox in kidney was localized and evaluated by immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting. The concentration of angiotensin II in kidney homogenates was determined using radioimmunoassay method.

Results

Compared with control, OS developed significantly in rats received EG, with increased expression of p47phox messenger RNA (mRNA) and protein in kidneys. Renal angiotensin II also increased significantly. Treatment with apocynin or losartan significantly reduced excretion of urinary 8-IP, restored SOD activity, with decrease in expression of p47phox in kidney, but levels of those OS markers in apocynin- or losartan-treated rats were still higher than in normal controls.

Conclusions

These results suggest that renal Ang II and its stimulation of NADPH oxidase may partially account for the development of OS in kidney in this rat model of CaOx nephrolithiasis.
Literatur
4.
Zurück zum Zitat Huang H-S, Ma M-C, Chen C-F, Chen J (2003) Lipid peroxidation and its correlations with urinary levels of oxalate, citric acid, and osteopontin in patients with renal calcium oxalate stones. Urology 61:1123–1128. doi:10.1016/S0090-4295(03)00764-7 CrossRef Huang H-S, Ma M-C, Chen C-F, Chen J (2003) Lipid peroxidation and its correlations with urinary levels of oxalate, citric acid, and osteopontin in patients with renal calcium oxalate stones. Urology 61:1123–1128. doi:10.​1016/​S0090-4295(03)00764-7 CrossRef
5.
Zurück zum Zitat Tungsanga K, Sriboonlue P, Futrakul P, Yachantha C, Tosukhowong P (2005) Renal tubular cell damage and oxidative stress in renal stone patients and the effect of potassium citrate treatment. Urol Res 33:65–69. doi:10.1007/s00240-004-0444-4 CrossRefPubMed Tungsanga K, Sriboonlue P, Futrakul P, Yachantha C, Tosukhowong P (2005) Renal tubular cell damage and oxidative stress in renal stone patients and the effect of potassium citrate treatment. Urol Res 33:65–69. doi:10.​1007/​s00240-004-0444-4 CrossRefPubMed
10.
Zurück zum Zitat Umekawa T, Byer K, Uemura H, Khan SR (2005) Diphenyleneiodium (DPI) reduces oxalate ion- and calcium oxalate monohydrate and brushite crystal-induced upregulation of MCP-1 in NRK 52E cells. Nephrol Dial Transplant 20:870–878. doi:10.1093/ndt/gfh750 CrossRefPubMed Umekawa T, Byer K, Uemura H, Khan SR (2005) Diphenyleneiodium (DPI) reduces oxalate ion- and calcium oxalate monohydrate and brushite crystal-induced upregulation of MCP-1 in NRK 52E cells. Nephrol Dial Transplant 20:870–878. doi:10.​1093/​ndt/​gfh750 CrossRefPubMed
11.
Zurück zum Zitat Itoh Y, Yasui T, Okada A, Tozawa K, Hayashi Y, Kohri K (2005) Preventive effects of green tea on renal stone formation and the role of oxidative stress in nephrolithiasis. J Urol 173:271–275PubMed Itoh Y, Yasui T, Okada A, Tozawa K, Hayashi Y, Kohri K (2005) Preventive effects of green tea on renal stone formation and the role of oxidative stress in nephrolithiasis. J Urol 173:271–275PubMed
12.
Zurück zum Zitat Thamilselvan S, Byer KJ, Hackett RL, Khan SR (2000) Free radical scavengers, catalase and superoxide dismutase provide protection from oxalate-associated injury to LLC-PK1 and MDCK cells. J Urol 164:230–236. doi:10.1016/S0022-5347(05)67499-X CrossRef Thamilselvan S, Byer KJ, Hackett RL, Khan SR (2000) Free radical scavengers, catalase and superoxide dismutase provide protection from oxalate-associated injury to LLC-PK1 and MDCK cells. J Urol 164:230–236. doi:10.​1016/​S0022-5347(05)67499-X CrossRef
13.
Zurück zum Zitat Thamilselvan S, Khan SR, Menon M (2003) Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants. Urol Res 31:3–9PubMed Thamilselvan S, Khan SR, Menon M (2003) Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants. Urol Res 31:3–9PubMed
17.
Zurück zum Zitat Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501PubMed Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501PubMed
20.
Zurück zum Zitat Paliege A, Parsumathy A, Mizel D, Yang T, Schnermann J, Bachmann S (2006) Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 290:R694–R700. doi:10.1152/ajpregu.00219.2005 PubMed Paliege A, Parsumathy A, Mizel D, Yang T, Schnermann J, Bachmann S (2006) Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 290:R694–R700. doi:10.​1152/​ajpregu.​00219.​2005 PubMed
21.
Zurück zum Zitat Rashed T, Menon M, Thamilselvan S (2004) Molecular mechanism of oxalate-induced free radical production and glutathione redox imbalance in renal epithelial cells: effect of antioxidants. Am J Nephrol 24:557–568. doi:10.1159/000082043 CrossRefPubMed Rashed T, Menon M, Thamilselvan S (2004) Molecular mechanism of oxalate-induced free radical production and glutathione redox imbalance in renal epithelial cells: effect of antioxidants. Am J Nephrol 24:557–568. doi:10.​1159/​000082043 CrossRefPubMed
24.
Zurück zum Zitat Toblli JE, Ferder L, Stella I, De Cavanagh MVE, Angerosa M, Inserra F (2002) Effects of angiotensin II subtype 1 receptor blockade by losartan on tubulointerstitial lesions caused by hyperoxaluria. J Urol 168:1550–1555. doi:10.1016/S0022-5347(05)64519-3 CrossRefPubMed Toblli JE, Ferder L, Stella I, De Cavanagh MVE, Angerosa M, Inserra F (2002) Effects of angiotensin II subtype 1 receptor blockade by losartan on tubulointerstitial lesions caused by hyperoxaluria. J Urol 168:1550–1555. doi:10.​1016/​S0022-5347(05)64519-3 CrossRefPubMed
25.
31.
Zurück zum Zitat Khan SR, Glenton PA, Byer KJ (2006) Modeling of hyperoxaluric calcium oxalate nephrolithiasis: experimental induction of hyperoxaluria by hydroxyl-L-proline. Kidney Int 165:1173–1181 Khan SR, Glenton PA, Byer KJ (2006) Modeling of hyperoxaluric calcium oxalate nephrolithiasis: experimental induction of hyperoxaluria by hydroxyl-L-proline. Kidney Int 165:1173–1181
35.
Zurück zum Zitat Chabrashvili T, Tojo A, Onozato ML, Kitiyakara C, Quinn MT, Fujita T, Welch WJ, Wilcox CS (2002) Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney. Hypertension 39:269–274. doi:10.1161/hy0202.103264 CrossRefPubMed Chabrashvili T, Tojo A, Onozato ML, Kitiyakara C, Quinn MT, Fujita T, Welch WJ, Wilcox CS (2002) Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney. Hypertension 39:269–274. doi:10.​1161/​hy0202.​103264 CrossRefPubMed
37.
Zurück zum Zitat Yasunari K, Maeda K, Nakamura M, Yoshikawa J (2002) Pressure promotes angiotensin II-mediated migration of human coronary smooth muscle cells through increase in oxidative stress. Hypertension 39:433–437. doi:10.1161/hy02t2.102991 CrossRefPubMed Yasunari K, Maeda K, Nakamura M, Yoshikawa J (2002) Pressure promotes angiotensin II-mediated migration of human coronary smooth muscle cells through increase in oxidative stress. Hypertension 39:433–437. doi:10.​1161/​hy02t2.​102991 CrossRefPubMed
38.
39.
40.
Zurück zum Zitat Antus B, Exton MS, Rosivall L (2001) Angiotensin II. A regulator of inflammation during renal disease? Int J Immunopathol Pharmacol 14:25–30PubMed Antus B, Exton MS, Rosivall L (2001) Angiotensin II. A regulator of inflammation during renal disease? Int J Immunopathol Pharmacol 14:25–30PubMed
Metadaten
Titel
Effects of apocynin and losartan treatment on renal oxidative stress in a rat model of calcium oxalate nephrolithiasis
verfasst von
Cheng-yang Li
Yao-liang Deng
Bing-hua Sun
Publikationsdatum
01.12.2009
Verlag
Springer Netherlands
Erschienen in
International Urology and Nephrology / Ausgabe 4/2009
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-009-9534-0

Weitere Artikel der Ausgabe 4/2009

International Urology and Nephrology 4/2009 Zur Ausgabe

Urology - Editorial

Editorial comment

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

„Überwältigende“ Evidenz für Tripeltherapie beim metastasierten Prostata-Ca.

22.05.2024 Prostatakarzinom Nachrichten

Patienten mit metastasiertem hormonsensitivem Prostatakarzinom sollten nicht mehr mit einer alleinigen Androgendeprivationstherapie (ADT) behandelt werden, mahnt ein US-Team nach Sichtung der aktuellen Datenlage. Mit einer Tripeltherapie haben die Betroffenen offenbar die besten Überlebenschancen.

So sicher sind Tattoos: Neue Daten zur Risikobewertung

22.05.2024 Melanom Nachrichten

Das größte medizinische Problem bei Tattoos bleiben allergische Reaktionen. Melanome werden dadurch offensichtlich nicht gefördert, die Farbpigmente könnten aber andere Tumoren begünstigen.

CAR-M-Zellen: Warten auf das große Fressen

22.05.2024 Onkologische Immuntherapie Nachrichten

Auch myeloide Immunzellen lassen sich mit chimären Antigenrezeptoren gegen Tumoren ausstatten. Solche CAR-Fresszell-Therapien werden jetzt für solide Tumoren entwickelt. Künftig soll dieser Prozess nicht mehr ex vivo, sondern per mRNA im Körper der Betroffenen erfolgen.

Frühzeitige HbA1c-Kontrolle macht sich lebenslang bemerkbar

22.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes von Anfang an intensiv BZ-senkend zu behandeln, wirkt sich positiv auf Komplikationen und Mortalität aus – und das offenbar lebenslang, wie eine weitere Nachfolgeuntersuchung der UKPD-Studie nahelegt.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.