Aluminum Exacerbates Cyclosporin Induced Nephrotoxicity in Rats

Tariq, Mohammad; Morais, Christudas; Sujata, Balija; Sobki, Samia H.; Sulaiman, Mohammed Al; Khader, Abdullah Al

doi:10.3109/08860229909066968

Cited by 6 publications

(7 citation statements)

References 31 publications

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“…Ciclosporin A (CsA) is considered the prototype of a new generation of immunosuppressants which has revolutionized the management of allotransplantation [1, 2, 3]. This drug specifically inhibits immunocompetent T helper lymphocytes by suppressing the interleukin 2 driven proliferation of activated T cells [4, 5, 6].…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…[15][16][17][18]36] As mentioned above, reactive oxygen species are indicated as a contributing factor in cyclosporine nephrotoxicity. [4][5][6][7][8] Based on this knowledge, we were expecting to find increased oxidative stress in kidneys after the concurrent use of hyperbaric oxygen and cyclosporine. Surprisingly, hyperbaric oxygen significantly improved oxidative stress parameters; renal lipid peroxidation decreased and antioxidant enzyme activities increased.…”

Section: Discussionmentioning

confidence: 98%

“…Recent studies clearly demonstrate that reactive oxygen species play a pivotal role in the development of cisplatin-induced renal dysfunction. [4][5][6][7][8] Cyclosporine causes renal ischemia by increasing renal vascular resistance and decreasing renal blood flow. [27] Cyclosporine induced ischemic injury in the kidney leads to the overproduction of reactive oxygen species and lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

“…[12] However, both hyperbaric oxygen and cyclosporine interact with drugs used concurrently, which may result in potentiation of their toxic effects. [6,7,13] In a recent study, we investigated the effect of hyperbaric oxygen on acute cyclosporine nephrotoxicity. [13] Animals received cyclosporine (25 mg/kg/day) and hyperbaric oxygen (60 min at 2.5 atmosphere absolute (ATA)/day) treatments concurrently for four days.…”

Section: Introductionmentioning

confidence: 99%

“…[3] Evidence derived from various studies suggests that reactive oxygen species could be one of the mediators involved in the pathogenesis of cyclosporine nephrotoxicity. [4][5][6][7][8] Reactive oxygen species are toxic to cells because they react with and damage cellular proteins, membrane lipids, and DNA. [9] This hypothesis was supported by studies reporting the protective effects of antioxidants against cyclosporine nephrotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Hyperbaric Oxygen on Cyclosporine-Induced Nephrotoxicity and Oxidative Stress in Rats

Uzun

Önem

et al. 2007

Renal Failure

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Reactive oxygen species have been suggested to be involved in cyclosporine nephrotoxicity. Hyperbaric oxygen is known to induce the generation of reactive oxygen species in tissues. The aim of this study was to investigate whether the use of hyperbaric oxygen concurrently with cyclosporine potentiates cyclosporine nephrotoxicity by inducing oxidative stress in kidneys. The study consisted of four groups of rats: a control group, a cyclosporine group (15 mg/kg/day intraperitoneally for 14 days), a hyperbaric oxygen group (60 min. every day for five days at 2.5 atmosphere absolute), and a cyclosporine + hyperbaric oxygen group (cyclosporine 15 mg/kg/day intraperitoneally for 14 days + hyperbaric oxygen for 60 min at 2.5 atmosphere absolute every day for five days on the last five days of cyclosporine treatment). Oxidative stress was determined by measuring renal thiobarbituric acid-reactive substances content, renal superoxide dismutase, and glutathione peroxidase activities. Cyclosporine increased serum urea and creatinine levels, indicating the development of nephrotoxicity, and induced significant oxidative stress in rat kidneys. Hyperbaric oxygen alone did not alter any of the biochemical and oxidative stress parameters compared to the control group. When used concurrently with cyclosporine, hyperbaric oxygen significantly reduced cyclosporine-induced oxidative stress, but it neither attenuated nor aggravated cyclosporine-induced nephrotoxicity. These results suggest that reactive oxygen species are involved in cyclosporine nephrotoxicity, but are not the direct cause of the toxicity. Although concurrent use of cyclosporine and hyperbaric oxygen did not exacerbate cyclosporine nephrotoxicity in this model, we recommend that the renal functions of patients be monitored periodically when these treatments are used concurrently.

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Attenuating the increased level of creatinine by N‐acetylcysteine: Raman spectroscopy and density functional theory‐based monitoring of in vitro complexation in aqueous solution

Gangopadhyay

Das

Singh

et al. 2020

J Raman Spectroscopy

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The role of drug N‐acetylcysteine (NAC) in preventing contrast‐induced nephropathy (CIN) and kidney diseases has been investigated with the help of in vitro Raman spectroscopy and density functional theory (DFT). Renal dysfunction or kidney failure is diagnosed by an increase in serum creatinine (CRN). The exposure to contrast agents during angiography also causes an increase in serum CRN, a condition termed as CIN. NAC is given to such patients, as it is known to prevent the toxic effect of CRN, although its mechanism of action is not clearly known till date. In the present study, we have studied the interaction between CRN and NAC and tried to detect the formation of a stable complex between the two by analyzing the in vitro Raman spectra of aqueous solutions of CRN and NAC mixed in different molar ratios. From the Raman spectral analysis, it is observed that a stable complex is formed at 1:1 molar ratio of CRN and NAC. This complex has been synthesized in the laboratory, and upon drying, it is transparent, gel‐like in appearance, and slightly yellowish in color. The complex is hygroscopic and has much better water solubility than CRN. Fourier‐transform infrared (FT‐IR) and Raman spectral analyses of the synthesized complex show the structural changes taking place because of complexation and provide proof that the complex is stable at room temperature. DFT‐based studies on a number of plausible structures of the complex have also been done to determine the most stable structure of the complex, and the mechanism of its formation has been explored by transition‐state calculations. This study highlights the effective role of NAC in reducing the toxic effect of CRN as the water‐soluble complex of CRN, and NAC is likely to be removed through urine.

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Aluminum Exacerbates Cyclosporin Induced Nephrotoxicity in Rats

Cited by 6 publications

References 31 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?

Effect of Hyperbaric Oxygen on Cyclosporine-Induced Nephrotoxicity and Oxidative Stress in Rats

Attenuating the increased level of creatinine by N‐acetylcysteine: Raman spectroscopy and density functional theory‐based monitoring of in vitro complexation in aqueous solution

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