Antineoplastic Efficacy of Cisplatin(CP) on LLC-WRC 256 Tumor Cells Is Not Reduced by the Protective Effect of Iron Chelator (IC), Hydroxyl Radical Scavenger(HRS) and Cytochrome P-450(CYP) Inhibitors against CP-Induced Nephrotoxicity

Reactive oxygen metabolites, in particular hydroxyl radical, have been shown to be important mediators of tissue injury in several models of acute renal failure. The aim of the present study was to examine the role of hydroxyl radical in glycerol-induced acute renal failure, a model for myoglobinuric renal injury. Rats injected with glycerol alone (8 mg/kg im following dehydration for 24 h) developed significant renal failure compared with dehydrated controls. Rats treated with glycerol and a hydroxyl radical scavenger, dimethylthiourea (DMTU), had significantly lower blood urea nitrogen (BUN) and creatinine. In contrast, urea, which is chemically similar to DMTU but is not a hydroxyl radical scavenger, provided no protection. In addition, DMTU prevented the glycerol-induced rise in renal cortical malondialdehyde content (a measure of lipid peroxidation that serves as a marker of free radical-mediated tissue injury). A second hydroxyl radical scavenger, sodium benzoate, had a similar protective effect on renal function (as measured by both BUN and creatinine). Because the generation of hydroxyl radical in biological systems requires the presence of a trace metal such as iron, we also examined the effect of the iron chelator, deferoxamine on glycerol-induced renal failure. Deferoxamine was also protective. The interventional agents were also associated with a marked reduction in histological evidence of renal damage. The protective effects of two hydroxyl radical scavengers as well as an iron chelator implicate a role for hydroxyl radical in glycerol-induced acute renal failure.

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Protective effect of thiourea, a hydroxyl-radical scavenger, on curcumin-induced chromosomal aberrations in an in vitro mammalian cell system

Teratogenesis Carcinogenesis and Mutagenesis ◽

10.1002/1520-6866(2001)21:2<175::aid-tcm6>3.0.co;2-v ◽

2001 ◽

Vol 21 (2) ◽

pp. 175-180 ◽

Cited By ~ 19

Author(s):

Maria Cristina P. Ara�jo ◽

Lus�nia M.G. Antunes ◽

Catarina S. Takahashi

Keyword(s):

Protective Effect ◽

Hydroxyl Radical ◽

Mammalian Cell ◽

Chromosomal Aberrations ◽

Cell System ◽

Radical Scavenger ◽

Hydroxyl Radical Scavenger

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Contribution of Oxidative Damage to Antimicrobial Lethality

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01087-08 ◽

2009 ◽

Vol 53 (4) ◽

pp. 1395-1402 ◽

Cited By ~ 129

Author(s):

Xiuhong Wang ◽

Xilin Zhao

Keyword(s):

Oxidative Stress ◽

Escherichia Coli ◽

Hydroxyl Radical ◽

Hydroxyl Radicals ◽

Fenton Reaction ◽

Iron Chelator ◽

Radical Scavenger ◽

Alkyl Hydroperoxide ◽

Hydroxyl Radical Scavenger ◽

Rapid Conversion

ABSTRACT A potential pathway linking hydroxyl radicals to antimicrobial lethality was examined by using mutational and chemical perturbations of Escherichia coli. Deficiencies of sodA or sodB had no effect on norfloxacin lethality; however, the absence of both genes together reduced lethal activity, consistent with rapid conversion of excessive superoxide to hydrogen peroxide contributing to quinolone lethality. Norfloxacin was more lethal with a mutant deficient in katG than with its isogenic parent, suggesting that detoxification of peroxide to water normally reduces quinolone lethality. An iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) reduced the lethal activity of norfloxacin, indicating that norfloxacin-stimulated accumulation of peroxide affects lethal activity via hydroxyl radicals generated through the Fenton reaction. Ampicillin and kanamycin, antibacterials unrelated to fluoroquinolones, displayed behavior similar to that of norfloxacin except that these two agents showed hyperlethality with an ahpC (alkyl hydroperoxide reductase) mutant rather than with a katG mutant. Collectively, these data are consistent with antimicrobial stress increasing the production of superoxide, which then undergoes dismutation to peroxide, from which a highly toxic hydroxyl radical is generated. Hydroxyl radicals then enhance antimicrobial lethality, as suggested by earlier work. Such findings indicate that oxidative stress networks may provide targets for antimicrobial potentiation.

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Ischemia-reperfusion injury of the spinal cord: Protective effect of the hydroxyl radical scavenger dimethylthiourea

Journal of Vascular Surgery ◽

10.1016/0741-5214(94)90144-9 ◽

1994 ◽

Vol 20 (3) ◽

pp. 444-450 ◽

Cited By ~ 30

Author(s):

Willem Wisselink ◽

Samuel R. Money ◽

Donald E. Crockett ◽

Justin H. Nguyen ◽

Mark O. Becker ◽

...

Keyword(s):

Spinal Cord ◽

Protective Effect ◽

Hydroxyl Radical ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Radical Scavenger ◽

Hydroxyl Radical Scavenger

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Evidence suggesting a role for hydroxyl radical in passive Heymann nephritis in rats

AJP Renal Physiology ◽

10.1152/ajprenal.1988.254.3.f337 ◽

1988 ◽

Vol 254 (3) ◽

pp. F337-F344 ◽

Cited By ~ 6

Author(s):

S. V. Shah

Keyword(s):

Hydroxyl Radical ◽

Marked Reduction ◽

Iron Chelator ◽

Radical Scavenger ◽

Reactive Oxygen Metabolites ◽

Heymann Nephritis ◽

Hydroxyl Radical Scavenger ◽

And Control ◽

Complement Deposition ◽

Oxygen Metabolites

We examined the effect of scavengers of reactive oxygen metabolites on proteinuria in the passive Heymann nephritis model of membranous nephropathy. Passive Heymann nephritis was induced by a single intravenous injection of anti-Fx1A IgG in a dose of 10 mg/100 g body weight. Superoxide dismutase, a scavenger of superoxide or catalase which destroys hydrogen peroxide, did not affect the proteinuria. In contrast, dimethylthiourea (DMTU, 500 mg/kg followed by 125 mg/kg ip twice a day), a scavenger of hydroxyl radical, markedly reduced the proteinuria (day 5: anti-Fx1A 53 +/- 13, n = 18; anti-Fx1A + DMTU, 21 +/- 6 mg/24 h, n = 15, P less than 0.001). Experiments with 125I-labeled anti-Fx1A antibody demonstrated that DMTU did not affect the amount of antibody deposited in the kidney. Semiquantitative estimation of IgG and complement deposition in the kidney showed no differences between the DMTU-treated and control rats. A second hydroxyl radical scavenger, sodium benzoate (150 mg/kg ip twice a day), also resulted in marked reduction in proteinuria (day 5: anti-Fx1A 56 +/- 7, n = 9; anti-Fx1A + benzoate, 14 +/- 4 mg/24 h, n = 8, P less than 0.01). Because of the participation of iron in biological systems to generate hydroxyl radical, we also examined the effect of deferoxamine (DFO, 35 mg/day), an iron chelator, on the anti-Fx1A-induced proteinuria. There was a significant reduction in proteinuria in rats treated concurrently with DFO (day 5: anti-Fx1A 67 +/- 13, n = 15; anti-Fx1A + DFO, 29 +/- 4 mg/24 h, n = 15, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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