Biological spin trapping II. Toxicity of nitrone spin traps: dose-ranging in the rat

Janzen, Edward G.; Poyer, J. Lee; Schaefer, Carl F.; Downs, P.; Dubose, Coit M.

doi:10.1016/0165-022x(95)00012-1

Cited by 55 publications

(30 citation statements)

References 10 publications

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“…At 50 mM, DMPO does not affect trypan blue exclusion or the clonogenicity of Chinese hamster ovary cells, but it does prevent colony formation by 9L tumor cells [30]. DMPO administered to Sprague Dawley rats at 2.32 g/kg body weight (average concentration of 20.5 mM) is nontoxic, so that necessarily high concentrations of DMPO can be used with little side effect [12]. …”

Section: Considerations In the Use Of Dmpo To Study Protein Radicamentioning

confidence: 99%

“…Because of their physico-chemical properties, membrane permeability [10–11], effectiveness at trapping free radicals [9], and low toxicity [12], nitrone spin traps have been employed both as reagents to detect radicals using ESR spectroscopy [7, 9] and as pharmacological agents against oxidative stress-mediated injury [13–14]. The most popular of these spin traps is 5,5-dimethyl-1-pyrroline N -oxide (DMPO) [15], which has been cited in Medline over 1,300 times.…”

Section: Introductionmentioning

confidence: 99%

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Immuno-spin trapping from biochemistry to medicine: Advances, challenges, and pitfalls. Focus on protein-centered radicals

Gomez-Mejiba

Zhai

Vedova

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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BACKGROUND Immuno-spin trapping (IST) is based on the reaction of a spin trap with a free radical to form a stable nitrone adduct, followed by the use of antibodies, rather than traditional electron paramagnetic resonance spectroscopy, to detect the nitrone adduct. IST has been successfully applied to mechanistic in vitro studies, and recently, macromolecule-centered radicals have been detected in models of drug-induced agranulocytosis, hepatotoxicity, cardiotoxicity, and ischemia/reperfusion, as well as in models of neurological, metabolic and immunological diseases. SCOPE OF THE REVIEW To critically evaluate advances, challenges, and pitfalls as well as the scientific opportunities of IST as applied to the study of protein-centered free radicals generated in stressed organelles, cells, tissues and animal models of disease and exposure. MAJOR CONCLUSIONS Because the spin trap has to be present at high enough concentrations in the microenvironment where the radical is formed, the possible effects of the spin trap on gene expression, metabolism and cell physiology have to be considered in the use of IST and in the interpretation of results. These factors have not yet been thoroughly dealt with in the literature. GENERAL SIGNIFICANCE The identification of radicalized proteins during cell/tissue response to stressors will help define their role in the complex cellular response to stressors and pathogenesis; however, the fidelity of spin trapping/ immuno-detection and the effects of the spin trap on the biological system should be considered.

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Section: Considerations In the Use Of Dmpo To Study Protein Radicamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immuno-spin trapping from biochemistry to medicine: Advances, challenges, and pitfalls. Focus on protein-centered radicals

Gomez-Mejiba

Zhai

Vedova

et al. 2014

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…The remaining groups (NEP and EP) were injected in a similar manner during weeks 9 and 10, every other day and 1 h before exercise, with 13 mg per 100 g of body weight of PBN diluted in saline. 9 One day after the last training session, animals were killed by decapitation, the spinal cord was extracted and the cervical region was separated. The cervical section was chosen because this is a frequently injured part of the spinal cord, and injury is known to be associated with ROS production.…”

Section: Animalsmentioning

confidence: 99%

The effect of exercise and oxidant–antioxidant intervention on the levels of neurotrophins and free radicals in spinal cord of rats

et al. 2008

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Study design: This study was designed to investigate the effects of oxidant and antioxidant treatment, as well as regular exercise, on neurotrophin levels in the spinal cord of rats. Objectives: Reactive oxygen species (ROS) play a role in neurodegenerative diseases, but ROS at moderate levels could stimulate biochemical processes through redox-sensitive transcription. Methods: Exercised or sedentary animals were injected subcutaneously with hydrogen peroxide (H 2 O 2 ), N-tert butyl-a-phenyl nitrone (PBN) or saline for the last 2 weeks of a 10-week experimental period to challenge redox balance. Free radical (FR) concentration was evaluated in the spinal cord by electron spin resonance, protein carbonyls, brain-derived neurotrophic factor (BDNF), glial cell linederived neurotrophic factor (GDNF) levels and the mRNA expression of BDNF receptor and tyrosine kinase receptor B (TrKB). Setting: Research Institute of Sport Science, Semmelweis University, Budapest, Hungary. Results: Exercise or PBN decreased the concentration of FR, whereas the carbonyl content did not change. BDNF was significantly decreased in exercised sham and sedentary PBN-treated groups, and its content correlated with the level of FR. GDNF was significantly increased in sedentary H 2 O 2 -treated groups. No differences were observed in TrkB mRNA expression among groups. Conclusions: Results suggest that regular exercise alone and PBN in sedentary animals can successfully decrease FR levels in the spinal cord. Redox alteration seems to affect the levels of GDNF and BDNF, which might have clinical consequences, as neurotrophins play an important role in cellular resistance and regeneration.

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“…The nitrone spin trap 5,5-dimethyl-1-pyrroline N -oxide (DMPO) was first introduced by Janzen and his colleagues about 40 years ago [3]. Since then, DMPO has been widely used in the ESR spin trapping technique and is becoming the most popular nitrone spin trap in free radical research [4, 5]. DMPO received extra attention during the last 10 years due to the development of an anti-DMPO antibody, which has largely expanded the application of DMPO in the study of free radicals in biological systems ([6] and references cited therein).…”

Section: Introductionmentioning

confidence: 99%

The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide Affects Stress Response and Fate of Lipopolysaccharide-Primed RAW 264.7 Macrophage Cells

2012

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The nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) is commonly used to study free radicals. Due to its free radical trapping properties, DMPO is thought to reduce free radial-mediated oxidative damage and other related cellular responses. The purpose of this study was to assess the effect of DMPO on lipopolysaccharide (LPS)-induced inflammation, endoplasmic reticulum (ER)-stress, and apoptosis in RAW 264.7 cells. The results showed that DMPO at 50 mM inhibited inducible nitric oxide synthase expression when added shortly after LPS treatment (≤3 h). Interestingly, DMPO increased anti-inflammatory heme oxygenase-1 (HO-1) expression and reversed LPS-induced decrease in HO-1 expression. LPS could increase cellular ER stress as indicated by CHOP induction; DMPO reduced LPS effect on CHOP expression. Unexpectedly, DMPO had a synergistic effect with LPS on increased caspase-3 activity. Overall, DMPO harbors multiple modulating effects, but may induce apoptosis in LPS-stressed cells when given at 50 mM, an effective dose for its anti-inflammatory activity in vitro. Our data provide clues for further understanding of DMPO, the old nitrone spin trap with therapeutic potential.

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Biological spin trapping II. Toxicity of nitrone spin traps: dose-ranging in the rat

Cited by 55 publications

References 10 publications

Immuno-spin trapping from biochemistry to medicine: Advances, challenges, and pitfalls. Focus on protein-centered radicals

Immuno-spin trapping from biochemistry to medicine: Advances, challenges, and pitfalls. Focus on protein-centered radicals

The effect of exercise and oxidant–antioxidant intervention on the levels of neurotrophins and free radicals in spinal cord of rats

The Nitrone Spin Trap 5,5-Dimethyl-1-pyrroline N-oxide Affects Stress Response and Fate of Lipopolysaccharide-Primed RAW 264.7 Macrophage Cells

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