Melatonin Prevents Cyclosporine-induced Nephrotoxicity in Isolated and Perfused Rat Kidney

Longoni, Biancamaria; Migliori, Massimiliano; Ferretti, Agnese; Origlia, Nicola; Panichi, Vincenzo; Boggi, Ugo; Filippi, C.; Cuttano, Maria Giuseppa; Giovannini, Luca; Mosca, Franco

doi:10.1080/10715760290019381

Cited by 30 publications

(14 citation statements)

References 40 publications

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“…This result suggests that SP blocks the occurrence of NO and therefore it has a supportive effect on the antioxidant system. Similar antioxidant properties have also been reported in studies using ischaemia re-perfusion injury in the rat brain (Longoni et al, 2002).…”

Section: Discussionsupporting

confidence: 54%

Spirulina platensis protects against gentamicin‐induced nephrotoxicity in rats

Karadeniz

Yıldırım

Şimşek

et al. 2008

Phytotherapy Research

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The present study aimed to investigate the protective effect of Spirulina platensis (SP) on gentamicin sulphate (GS)-induced changes in the levels of lipid peroxidation and endogenous antioxidants in the kidney of rats. Sprague-Dawley rats were treated in separate groups as follows for 7 consecutive days: control (C), gentamicin sulphate (100 mg/kg i.p.) (GS), Spirulina platensis (1000 mg/kg orally) (SP) and Spirulina platensis (1000 mg/kg orally) plus gentamicin sulphate (100 mg/kg i.p.) (SP + GS). The degree of protection was evaluated by determining the effects of Spirulina platensis on malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX) and nitric oxide (NO), and plasma creatinine and urea levels were estimated in kidney homogenates to evaluate antioxidant activity, and the kidney was histologically examined as well. Spirulina platensis elicited significant nephroprotective activity by decreasing lipid peroxidation (MDA) and elevated the levels of GSH, SOD, GPX, NO, creatinine and urea. Furthermore, these biochemical observations were supplemented by histological examination of the rat kidneys. In conclusion, the present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Spirulina platensis in gentamicin sulphate induced nephrotoxicity.

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Section: Discussionsupporting

confidence: 54%

Spirulina platensis protects against gentamicin‐induced nephrotoxicity in rats

Karadeniz

Yıldırım

Şimşek

et al. 2008

Phytotherapy Research

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“…[28,29] Antioxidants such as vitamin E, trimetazidine, melatonin, and n-acetylcysteine have been shown to reduce cyclosporine-induced oxidative stress and prevent renal dysfunction. [8,[29][30][31] In agreement with previous studies, we determined a clear association between renal dysfunction and oxidative stress parameters in cyclosporine treated rats. However, mediators other than reactive oxygen species are also suggested to be involved in cyclosporine nephrotoxicity, including transforming growth factor B1, angiotensin II, nitric oxide, thromboxane A2, and leukotriene.…”

Section: Discussionsupporting

confidence: 90%

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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“…[4,5] Although many reports suggest that the pathophysiology of GEN-induced nephrotoxicity is unclear, researchers found that in GEN-treated rats, reactive oxygen species (ROS) including superoxide anion (O 2 −• ), [6] hydrogen peroxide (H 2 O 2 ), [7][8][9] and hydroxyl radicals (HO) were found to be enhanced in both in vivo (renal cortex) and in vitro (mitochondrial) models. It was also confirmed by others that ROS participate in all pathological conditions, including glomerular disease, [4] and in renal ischemia and reperfusion injury [10] and other toxic renal failure. [11] In addition, oxidative stress releases iron from mitochondria of renal cortex and forms an iron-GEN complex known as ferrous iron, which is a potent catalyst of free radicals and enhance the generation of ROS.…”

Section: Introductionmentioning

confidence: 50%

Nephroprotective Effect ofWithania somnifera:A Dose-Dependent Study

Jeyanthi

Subramanian

2009

Renal Failure

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In the present study, we investigated the protective effect of Withania somnifera, an indigenous medicinal herb used in ayurvedic traditional systems for more than 3000 years in India, on gentamicin (GEN)-induced nephrotoxicity. The root extract of three different doses of W. somnifera (viz., 250, 500, and 750 mg/kg) was administered orally to rats for 14 days before GEN treatment and thereafter concurrently with GEN (100 mg/kg) for 8 days. Nephrotoxicity was evident in GEN-treated rats by significant increase in kidney weight, urea, creatinine, urinary protein, and glucose, and significant reduction in body weights and potassium, which was histopathologically confirmed by tubular necrosis. In contrast W. somnifera (500 mg/kg) significantly reversed these changes as evidenced microscopically when compared to other two doses of W. somnifera (250 and 750 mg/kg), and there were no significant changes in the levels of sodium in the experimental animals compared to control. Thus, our results suggested the nephroprotective effect of Withania somnifera, which could be by enhancing antioxidant activity with natural antioxidants and scavenging the free radicals.

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Melatonin Prevents Cyclosporine-induced Nephrotoxicity in Isolated and Perfused Rat Kidney

Cited by 30 publications

References 40 publications

Spirulina platensis protects against gentamicin‐induced nephrotoxicity in rats

Spirulina platensis protects against gentamicin‐induced nephrotoxicity in rats

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

Nephroprotective Effect ofWithania somnifera:A Dose-Dependent Study

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