Impaired Antioxidant Defense System in the Kidney Tissues from Rabbits Treated with Cyclosporine

Durak, Zahide Esra; Karabacak, H. İbrahim; Büyükkoçak, Serap; Çimen, Mehmet; Kaçmaz, Murat; Ömeroglu, E.; Öztürk, Hasan Serdar

doi:10.1159/000044912

Cited by 92 publications

(61 citation statements)

References 12 publications

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“…The antioxidant vitamins C and E decreased the oxidative stress induced by CsA treatment in rabbit kidneys. They ameliorated the subcellular damage, so protecting the renal tissues from the toxic effects of the drug [32]. …”

Section: Discussionmentioning

confidence: 99%

Does Methylene Blue Protect the Kidney Tissues from Damage Induced by Ciclosporin A Treatment?

Rezzani

Rodella²,

Corsetti³

et al. 2001

Nephron

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Ciclosporin A (CsA) is the first-choice immunosuppressant universally used in allotransplantation and autoimmune diseases. However, it has been demonstrated that this drug produces negative side effects in several organs and in particular in the lymphoid organs and in the kidney. It has been suggested that the CsA causes deleterious effects because it increases the oxygen free radical production. Here we wanted to test whether antioxidants protect the kidney parenchyma from the toxicity induced by CsA. We used methylene blue (MB), because it inhibits the formation of oxygen free radicals. The study was carried out in four groups of Wistar rats. Group I animals were intraperitoneally injected with MB (1 mg/kg/day) for 21 days; group II animals were subcutaneously injected with CsA (15 mg/kg/day) for 21 days; group III animals were treated with CsA combined with MB at the same doses and for the same periods as groups I and II, and group IV animals were injected subcutaneously with olive oil for 21 days as controls. The kidneys and the thymuses were subsequently removed and examined by conventional morphological staining (hematoxylin-eosin and Masson’s trichrome) and enzymatic (NADPH-diaphorase, cytochrome, c oxidase, and superoxide anion production) and immunoenzymatic (inducible nitric oxide synthase – iNOS, endothelial nitric oxide synthase – eNOS) techniques. The thymuses were used to check the persistence of CsA-immunsuppressive effects during MB administration. Group I, III, and IV animals showed a normal kidney architecture and low levels of NADPH-diaphorase and of superoxide anion in all structures studied (proximal and distal tubules, glomeruli and the Henle loops). The cytochrome c oxidase showed a strong activity in proximal tubules, a moderate activity in distal tubules, and a weak activity in glomeruli and in the Henle loops. The expression of iNOS was weak in the proximal tubular epithelial cells and negative in the glomeruli, while eNOS was found to be moderately positive in the glomeruli and in the interstitial arteries, but not in the tubules and in the Henle loops. Degenerative changes with tubulointerstitial injury in the cortex of CsA-treated kidneys (group II) and increases of NADPH-diaphorase levels, iNOS activity, and superoxide staining were found in all structures. The expression of eNOS did not change in group I, III and IV animals. MB combined with CsA prevented the degenerative changes caused by CsA, preserving the structural, enzymatic, and immunoenzymatic integrity of the renal parenchyma. The mechanism by which MB exerts its protective action is not yet clear, but it seems to be due to its ability to inhibit xanthine oxidase and to quench nitric oxide production. Moreover, these data have been also supported by the following: (1) the superoxide anion levels were very high after CsA treatment and reduced after CsA-MB treatment, and (2) the iNOS levels increased in CsA-treated rats and showed normal levels after CsA-MB treatment. Moreover we demonstrated that MB administration did no co...

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Section: Discussionmentioning

confidence: 99%

Does Methylene Blue Protect the Kidney Tissues from Damage Induced by Ciclosporin A Treatment?

Rezzani

Rodella²,

Corsetti³

et al. 2001

Nephron

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“…The analysis parameters were studied in this fraction [16]. AOP was assessed according to the method described in table 1 [17], and the malondialdehyde (MDA) levels were measured as described previously [18]. …”

Section: Methodsmentioning

confidence: 99%

Antioxidant Defense Potential of Rabbit Renal Tissues after ESWL: Protective Effects of Antioxidant Vitamins

Biri

Öztürk²,

Büyükkoçak

et al. 1998

Nephron

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Antioxidant defense potential, malondialdehyde (MDA) levels, and relative hydroxyl radical (OH·) concentrations were measured in order to establish the effects of extracorporeal shock wave lithotripsy (ESWL) on free radical production and antioxidant defense potential of the rabbit kidney tissues. Electron microscopic examination was also performed to observe ultrastructural changes. The antioxidant defense potential of the ESWL-treated tissues was found to be reduced, and the MDA levels increased as compared with controls. Vitamin (vitamin E plus C combination) pretreatment ameliorated antioxidant defense potential in part, prevented increases in MDA levels in the ESWL-treated tissues, and increased the antioxidant defense potential in the control kidney tissues. After ESWL, a significant amount of OH· radical was measured in the affected tissue. This revealed the source of oxidant stress and peroxidation reactions in the ESWL-treated kidney tissue. Vitamin pretreatment caused significant reduction in the OH· radical concentration. In the electron microscopic investigation, some significant subcellular changes, such as endothelial injury, loss of foot processes, damage of glomerular basal membrane, etc., were observed in the ESWL-treated renal tissue slices. Vitamin pretreatment to a great extent prevented formation of these subcellular changes. Our results suggest that the antioxidant capacity of the kidney tissue was reduced after ESWL treatment and that the tissue was exposed to oxidant stress. Vitamin pretreatment exerted significant protection against the radical damage.

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“…The AOPs were measured by the method described by Durak et al (1998). Briefly, in the reaction medium enriched with fish oil, samples were exposed to a superoxide radical (O 2-) produced by the xanthine-xanthine oxidase system for 1 h and then MDA levels were measured as described by Dahle et al (1962).…”

Section: Blood Samplingmentioning

confidence: 99%

Comparison of flunixin meglumine and meloxicam influence on postoperative and oxidative stress in ovariohysterectomized bitches

Yilmaz¹,

Korkmaz²,

Jaroszewski³

et al. 2014

Polish Journal of Veterinary Sciences

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The aim of this study was to compare the effect of flunixin meglumine (FM) and meloxicam (M) on postoperative and oxidative stress in ovariohysterectomized bitches. Twenty four bitches were divided into three groups (n=8 in each) and treated during premedication as follows: FM (2.2 mg/kg, iv, Fluvil, Vilsan, Turkey), M (0.2 mg/kg, sc, Maxicam, Sanovel, Turkey) or 0.9% saline (1 ml, iv, IE, Turkey) -control (C) group. The concentrations of serum cortisol, nitric oxide (NO), malondialdehyde (MDA), antioxidant potential (AOP) and glutation (GSH) were measured in blood samples collected during incision (0 h), closure of incision line (0.5 h) and 1, 2.5, 12 and 24 hours after incision. It was observed that cortisol level was higher at 0.5, 1 and 2.5 h in group C (p < 0.05), 0.5 h in group FM (p < 0.001), and 1 and 2.5 h in group M (p < 0.01), as compared to that determine at 0 h. Group C showed higher cortisol level during 0.5 h (p < 0.05) than that found in the other groups. Group FM displayed lower levels during 1 h (p < 0.01) and 2.5 h (p < 0.05) as compared to those observed in other groups. Concentrations of MDA, AOP and GSH between all the groups did not show any significant differences. MDA level was higher at 0.5 and 1 h in group M (p < 0.05) than that found in group C and it was the lowest at 2.5 h in group C (p < 0.05). AOP was higher at 2.5 h in group FM and M (p < 0.05) than that observed in group C, and at 12 and 24 h in group M than that found in group C and FM. GSH did not show any significant differences between the groups. NO level in group FM after 12 h was higher (p < 0.05) than that at 0.5, 1 and 24 h. Moreover, NO level was lower at 0.5 (p < 0.01), 1 (p < 0.05) and 24 h (p < 0.05) in group FM than that observed in group C and M. In conclusion, flunixin meglumine decreases cortisol and NO levels more efficiently than meloxicam. Therefore, it is suggested that postoperative stress following ovariohysterectomy may be prevented by flunixin meglumine in bitches.

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Impaired Antioxidant Defense System in the Kidney Tissues from Rabbits Treated with Cyclosporine

Cited by 92 publications

References 12 publications

Does Methylene Blue Protect the Kidney Tissues from Damage Induced by Ciclosporin A Treatment?

Does Methylene Blue Protect the Kidney Tissues from Damage Induced by Ciclosporin A Treatment?

Antioxidant Defense Potential of Rabbit Renal Tissues after ESWL: Protective Effects of Antioxidant Vitamins

Comparison of flunixin meglumine and meloxicam influence on postoperative and oxidative stress in ovariohysterectomized bitches

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