The role of oxidative stress in paraquat-induced neurotoxicity in rats: protection by non peptidyl superoxide dismutase mimetic

Mollace, Vincenzo; Iannone, Michelangelo; Muscoli, Carolina; Palma, E; Granato, Teresa; Rispoli, Vincenzo; Nisticò, Robert; Rotiroti, Domenicantonio; Salvemini, Daniela

doi:10.1016/s0304-3940(02)01168-0

Cited by 71 publications

(41 citation statements)

References 15 publications

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“…8). Redox cycling is a primary cause of PQ-induced toxicity as evidenced by protection from adverse PQ effects by overexpression of superoxide dismutase (SOD) (108) or via administration of SOD mimetics (68). Conversely, deficiency in antioxidant enzymes causes hypersensitivity to PQ treatment in vivo (112).…”

Section: Paraquat Metabolism and Mitochondrial Mechanisms Of Neurotoxmentioning

confidence: 99%

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

Martinez

Greenamyre

2012

Antioxidants & Redox Signaling

217

155

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Significance: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the pathogenesis of both familial and idiopathic PD. In this review, we provide an overview of toxin models of mitochondrial dysfunction in experimental Parkinson's disease and discuss mitochondrial mechanisms of neurotoxicity. Recent Advances: A new toxin model using the mitochondrial toxin trichloroethylene was recently described and novel methods, such as intranasal exposure to toxins, have been explored. Additionally, recent research conducted in toxin models of parkinsonism provides an emerging emphasis on extranigral aspects of PD pathology. Critical Issues: Unfortunately, none of the existing animal models of experimental PD completely mimics the etiology, progression, and pathology of human PD. Future Directions: Continued efforts to optimize established animal models of parkinsonism, as well as the development and characterization of new animal models are essential, as there still remains a disconnect in terms of translating mechanistic observations in animal models of experimental PD into bona fide diseasemodifying therapeutics for human PD patients. Antioxid. Redox Signal. 16, 920-934.

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Section: Paraquat Metabolism and Mitochondrial Mechanisms Of Neurotoxmentioning

confidence: 99%

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

Martinez

Greenamyre

2012

Antioxidants & Redox Signaling

217

155

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“…Furthermore, SOD itself can have pro-oxidant effects at higher concentrations [16], [17], [18] and [19], for example, via the possibility that Cu 2+ derived from Cu/ZnSOD may facilitate the generation of oxidative stress in the presence of glutathione [17] or via the ability of superoxide to both initiate and terminate lipid peroxidation [19]. Subsequently, many different types of SOD mimetics (SODm) have been synthesized [15] and [20], including manganese(III) tetrakis(4-benzoic acid) porphyrin (MnTBAP) and M40401 (a manganese-containing SODm), which have been shown to reduce paraquat-induced lung and brain injury in the mouse and rat, respectively [21] and [22]. However, SODm also suffer problems regarding bioavailability and toxicity, e.g., their poor stability in vivo and pro-oxidant activities [23] and [24].…”

Section: Introductionmentioning

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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“…[19,20] The primary function of SODs is the detoxifi cation of cell-damaging superoxide anions, but they also play important roles in phytopathogensis since oxidative stress is an important component of the organism defense response against microbial invasion. [21] More importantly, ROS may attack mitochondria to induce the creation of apoptosome, which cleaves procaspase-3 to form caspase-3 and activates the apoptosis cascade. [22] Caspase-3 has been shown to be the end product for both external and internal apoptotic cascades.…”

Section: Discussionmentioning

confidence: 99%