Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats

Sueishi, Kunihiko; Mishima, Koji; Makino, Kazutaka; Itoh, Yoshinori; Tsuruya, Kazuhiko; Hirakata, Hideki; Oishi, Ryozo

doi:10.1016/s0014-2999(02)02251-3

Cited by 93 publications

(80 citation statements)

References 19 publications

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“…Accordingly, nephrotoxicity by cisplatin is characterized by renal electrolyte disturbances and by acute fall in glomerular filtration rate (GFR) [27,28]. Cisplatin teatment was found to cause diffuse tubular necrosis and desquamation and parenchyma degeneration in the cortex [29]. In the current study, turbular damage was similar to control kidney of a previous reportd study.…”

Section: Effect Of Fbg On Renal Tubular Damagesupporting

confidence: 77%

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Renoprotective Effects of Fermented Black Ginseng through Ameliorating Oxidative Stress Associated with Cisplatin-Induced Acute Nephrotoxicity in Mice

Roh¹,

Kwon²,

Seo³

2018

J Nutr Food Sci

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We aimed to evaluate the renal protective capacity of Fermented Black Ginseng (FBG) and its mechanism to reduce the cisplatin-induced nephrotoxicity. Nephrotoxicity was induced by a single intraperitoneal injection of cisplatin (20 mg/kg) and treated with white ginseng (WB) and FBG (200 mg/kg/day, orally) for 4 days before cisplatin treatment. Biochemical results showed that WG and FBG pretreatment significantly reduced the increase of blood urea nitrogen (BUN) and creatinine, and histopathological changes were meaningfully ameliorated. Cisplatin increased the production of reactive oxygen species (ROS) and depletion of Glutathione (GSH) in serum and kidney, whereas, WG or FBG administration markedly down-regulated. Moreover, the expression of nuclear factor-kappaB (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 was markedly suppressed by both WB and FBG. However, FBG pretreatment was more effective than those of WG in COX-2, iNOS, and IL-6 levels. Moreover, FBG treated mice significantly up-regulated the antioxidative enzymes. In HPLC analysis, the increasing ginsenoside contents that include Rg1, Re, Rb1, Rc, Rb3, Rd, Rg3, Rk1, and Rg5 by heat-processing were greater about 5.7 fold when fermentation additionally. Taken together, FBG may be a worthful candidate for the prevention of nephrotoxicity in patients receiving cisplatin.

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Section: Effect Of Fbg On Renal Tubular Damagesupporting

confidence: 77%

“…However, BUN and creatinine levels both WG and FBG were decreased significantly. Herein, pretreatment with WG and FBG attenuated cisplatin-induced renal dysfunction as demonstrated by normalization of BUN and creatinine level compared to cisplatin-control mice [27][28][29][30].…”

Section: Effect Of Fbg In Body and Kidney Weights And Serum Parametersmentioning

confidence: 93%

Renoprotective Effects of Fermented Black Ginseng through Ameliorating Oxidative Stress Associated with Cisplatin-Induced Acute Nephrotoxicity in Mice

Roh¹,

Kwon²,

Seo³

2018

J Nutr Food Sci

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“…Moreover, edaravone reduced mitochondrial damage in homogenate made from ischemic-incubated rat brain (Watanabe et al 1994). As compared with other antioxidants, edaravone has the following advantages: (1) it has already been used in clinical practice mostly without the presence of serious side effects at the dose currently applied (Sueishi et al 2002); (2) it is lipophilic, and therefore, readily accessible to tissues (Satoh et al 2003); (3) it preferentially accumulates in the kidneys (Spitz et al 2011). This accumulation in the kidneys is desirable because it presumably confers some selectivity towards the healthy tissue and favors nephroprotection.…”

Section: Discussionmentioning

confidence: 99%

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Chen

Liu

Dong

et al. 2015

Cell Stress and Chaperones

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Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p<0.05). Thus, the current study indicates that edaravone offers protection from radiation-induced cytogenetic alterations.

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“…[30] In animal models, the S3 segment of the proximal tubule appears to be major site of renal injury. [2,18,29,31] In humans, however, damage seems to occur primarily in the distal tubule and collecting ducts. [2,4,32,33] The present study shows that repeated injection of cisplatin (5 mg/kg, i.v., three times at 21-day intervals) induced histopathological and morphometric changes in rat kidney that were reversed to a considerable extent by the chronic administration of vitamin C (8 mg/kg, i.m., daily following the first injection of cisplatin for three months).…”

Section: Discussionmentioning

confidence: 99%

“…[12] Cisplatin-induced nephrotoxicity is closely associated with an increase in lipid peroxidation in the kidney tissues. [1,5,[13][14][15][16] This agent was able to generate reactive oxygen species (ROS), such as superoxide anions and hydroxyl radicals, [3,4,17,18] and inhibit the activity of antioxidant enzymes in renal tissues. [4,5,12] Cisplatin chemotherapy induces a fall in plasma antioxidant levels, which may reflect a failure of the antioxidant defense mechanism against oxidative damage induced by commonly used antitumor drugs.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Vitamin C on Cisplatin-Induced Renal Damage: A Light and Electron Microscopic Study

2008

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The present study was performed to investigate whether the chronic administration of antioxidant vitamin C provided morphological protection on cisplatin-induced renal damage. Wistar albino male rats were divided into control and two experiment groups, each consisting of six rats. Cisplatin (5 mg/kg/ month) was administered intravenously to the second and third group for three months. After the first application of cisplatin, vitamin C (8 mg/kg/day) to the third group was administered intramuscular for 3 months. At the end of the third month, the kidney specimens of the all groups were obtained. All of these kidney specimens were processed for light and electron microscopical examination. In the second group, most of the renal corpuscle lost their normal appearance and size, especially in the corticomedullary region. The most obvious changes were encountered in the proximal tubules. These changes were tubular dilation, thickening of basement membrane, loss of brush border, vacuolization, and swollenness of mitochondria in the proximal tubule epithelial cells. In addition, infiltration foci were observed mainly in the cortical region. In the third group, which was administered cisplatin plus vitamin C, although the structural damages and morphometric changes were lessened, mononuclear cell infiltration was still observed. This study suggests that the chronic administration of vitamin C may be of therapeutic benefit on cisplatin nephrotoxicity.

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Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats

Cited by 93 publications

References 19 publications

Renoprotective Effects of Fermented Black Ginseng through Ameliorating Oxidative Stress Associated with Cisplatin-Induced Acute Nephrotoxicity in Mice

Renoprotective Effects of Fermented Black Ginseng through Ameliorating Oxidative Stress Associated with Cisplatin-Induced Acute Nephrotoxicity in Mice

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage

Protective Effects of Vitamin C on Cisplatin-Induced Renal Damage: A Light and Electron Microscopic Study

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