A role for superoxide in gentamicin-mediated nephropathy in rats

Cuzzocrea, Salvatore; Mazzon, Emanuela; Dugo, Laura; Serraino, Ivana; Paola, Rosanna Di; Britti, Domenico; Sarro, Angela De; Pierpaoli, Simone; Caputi, Achille P.; Masini, Emanuela; Salvemini, Daniela

doi:10.1016/s0014-2999(02)01749-1

Cited by 247 publications

(191 citation statements)

References 40 publications

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“…Furthermore, SOD can have pro-oxidant activities at higher concentrations, e.g., Cu/ZnSOD can promote the generation of hydroxyl radicals [16] and [48] and inhibit the ability of superoxide to regulate lipid peroxidation [19] and [49]. This has generated much interest in SODm, leading to the development of agents including macrocyclics, manganese salens, nitroxides, porphyrins, and many other catalytic antioxidants [15], [20], [50], [51], [52], [53], [54] and [55]. However, many of these have also suffered problems ranging from cytotoxicity to poor stability [23] and [56].…”

Section: Discussionmentioning

confidence: 99%

“…However, the relatively safe profile of Mn(II) and Cu(II) complexes of EGTA and EHPG should allow investigations of these complexes in vivo to assess their efficacy against many pathological conditions involving ROS generation and oxidative stress. Specifically, these complexes could be investigated in models of ischemic or nephrotoxic ARF, which involve significant ROS generation and in which other SODm have been shown to provide beneficial effects [31], [32] and [51]. However, although there was no evidence of Cu(II) toxicity in this study, some care may need to be taken when Cu(II) complexes are utilized in view of a report that Cu(II) derived from Cu/ZnSOD may facilitate oxidative stress in the presence of glutathione [17].…”

Section: Discussionmentioning

confidence: 99%

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Reduction of paraquat-induced renal cytotoxicity by manganese and copper complexes of EGTA and EHPG

Samai

Hague

Naughton

et al. 2008

Free Radical Biology and Medicine

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Reduction of paraquat-induced renal cytotoxicity by manganese and copper complexes of EGTA and EHPG

Samai

Hague

Naughton

et al. 2008

Free Radical Biology and Medicine

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“…It has been shown that oxidative stress is involved in gentamicin-induced renal damage (24). There is also a marked decrease in glomerular filtration rate, ultrafiltration coefficient and glomerular plasma flow (25).…”

Section: Introductionmentioning

confidence: 99%

Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

Pessoa

Convento

Silva

et al. 2009

Braz J Med Biol Res

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Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU). After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM) and compared to untreated control or G/ IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO) and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 ± 4.3 to 6.5 ± 0.3%) and apoptosis (23.5 ± 4.3 to 6.5 ± 2.1%) and an increase in cell proliferation compared to G/IU. NO (0.177 ± 0.05 to 0.368 ± 0.073 μg/mg protein) and endothelin-1 (1.88 ± 0.47 to 2.75 ± 0.53 pg/mL) production significantly increased after 15 days of preconditioning compared to G/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed after preconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin.

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“…1) Unfortunately, 30% of patients treated with GM for more than 7 d show some signs of nephrotoxicity. 2,3) It has been reported that GM-induced nephrotoxicity is characterized by direct tubular necrosis, which is localized mainly in the proximal tubule.…”

mentioning

confidence: 99%

“…14) Among dietary flavonols, quercetin is by far the most abundant. Quercetin, (3,5,7,3Ј,4Ј-pentahydroxy flavone) 12) is a natural polyphenolic flavonoid widely found in edible plants (i.e. fruits, vegetables, herbs, grains) and beverages (i.e.…”

mentioning

confidence: 99%

Protective Effect of Quercetin against Gentamicin-Induced Nephrotoxicity in Rats

Abdel-Raheem

Abdelghany

Mohamed

2009

Biological & Pharmaceutical Bulletin

156

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Gentamicin (GM) is an antibiotic widely used in treating severe gram-negative infections. However, its clinical use is limited by its nephrotoxicity. Several lines of evidence indicate that free radicals are important mediators of gentamicin nephrotoxicity. Therefore, the aim of this work was to investigate the possible protective effect of the flavonoid quercetin, an antioxidant, on gentamicin-induced nephrotoxicity. For this purpose, rats were divided into four groups. First group served as a control and injected with the normal saline, second group was injected with quercetin (50 mg/kg/d, per os) for 7 d, third group was injected with gentamicin (80 mg/kg/d, intraperitoneally) for 7 d and the fourth group of animals was injected with quercetin plus gentamicin simultaneously for 7 d. Total protein levels were estimated in 24-h urine samples to assess kidney dysfunction. The rats were sacrificed on the seventh day and kidneys were collected for histopathological studies. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood. Moreover, glutathione (GSH), lipid peroxide (TBARS) levels, superoxide dismutase (SOD) and catalase (CAT) activities were determined in renal tissues. GM-treated rats showed early kidney dysfunction as urinary total protein, BUN and serum creatinine levels were significantly increased. The significant decrease in GSH levels, SOD, CAT activities and increase in TBARS levels, indicated that GMinduced nephrotoxicity was mediated through oxidative stress reactions. Histopathological examination of GM-treated rats revealed degenerative changes in glomeruli and tubules. On the other hand, simultaneous administration of quercetin plus gentamicin protected kidney tissues against nephrotoxic effects of gentamicin as evidenced from amelioration of histopathological changes and normalization of kidney biochemical parameters.

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A role for superoxide in gentamicin-mediated nephropathy in rats

Cited by 247 publications

References 40 publications

Reduction of paraquat-induced renal cytotoxicity by manganese and copper complexes of EGTA and EHPG

Reduction of paraquat-induced renal cytotoxicity by manganese and copper complexes of EGTA and EHPG

Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

Protective Effect of Quercetin against Gentamicin-Induced Nephrotoxicity in Rats

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