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Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10.

Somayajulu-Niţu M, Sandhu JK, Cohen J, Sikorska M, Sridhar TS, Matei A, Borowy-Borowski H, Pandey S - BMC Neurosci (2009)

Bottom Line: Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD.Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies.This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada. somayaj@uwindsor.ca

ABSTRACT

Background: Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance.

Results: Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod) evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats.

Conclusion: Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

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Oxidative stress markers. Experiment 2: Following behavioral testing, rats were sacrificed, midbrain tissue was homogenized and assayed for GSH (A) and MDA levels (B). Data (mean ± SEM) was normalized to that of saline injected placebo fed group, which was taken as 100%. (A) statistically significant differences (p < .001): *** between saline injected placebo fed group and paraquat injected placebo fed group; ### between paraquat injected placebo fed group and saline injected WS-CoQ10 fed group; HHH between paraquat injected placebo fed group and paraquat injected WS-CoQ10 fed group. (B) Statistically significant differences (p < .05): * between saline injected placebo fed group and paraquat injected placebo fed group; # between paraquat injected placebo fed group and saline injected WS-CoQ10 fed group; H between paraquat injected placebo fed group and paraquat injected WS-CoQ10 fed group.
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Figure 3: Oxidative stress markers. Experiment 2: Following behavioral testing, rats were sacrificed, midbrain tissue was homogenized and assayed for GSH (A) and MDA levels (B). Data (mean ± SEM) was normalized to that of saline injected placebo fed group, which was taken as 100%. (A) statistically significant differences (p < .001): *** between saline injected placebo fed group and paraquat injected placebo fed group; ### between paraquat injected placebo fed group and saline injected WS-CoQ10 fed group; HHH between paraquat injected placebo fed group and paraquat injected WS-CoQ10 fed group. (B) Statistically significant differences (p < .05): * between saline injected placebo fed group and paraquat injected placebo fed group; # between paraquat injected placebo fed group and saline injected WS-CoQ10 fed group; H between paraquat injected placebo fed group and paraquat injected WS-CoQ10 fed group.

Mentions: We measured the GSH content (Figure 3A) and lipid peroxidation (Figure 3B) in the midbrain of experimental animals as the markers of oxidative stress. We compared the levels of these markers in the brains of PQ-injected groups (Placebo and WS-CoQ10 fed groups) with the saline injected groups (Placebo and WS-CoQ10 fed groups).


Paraquat induces oxidative stress, neuronal loss in substantia nigra region and parkinsonism in adult rats: neuroprotection and amelioration of symptoms by water-soluble formulation of coenzyme Q10.

Somayajulu-Niţu M, Sandhu JK, Cohen J, Sikorska M, Sridhar TS, Matei A, Borowy-Borowski H, Pandey S - BMC Neurosci (2009)

Oxidative stress markers. Experiment 2: Following behavioral testing, rats were sacrificed, midbrain tissue was homogenized and assayed for GSH (A) and MDA levels (B). Data (mean ± SEM) was normalized to that of saline injected placebo fed group, which was taken as 100%. (A) statistically significant differences (p < .001): *** between saline injected placebo fed group and paraquat injected placebo fed group; ### between paraquat injected placebo fed group and saline injected WS-CoQ10 fed group; HHH between paraquat injected placebo fed group and paraquat injected WS-CoQ10 fed group. (B) Statistically significant differences (p < .05): * between saline injected placebo fed group and paraquat injected placebo fed group; # between paraquat injected placebo fed group and saline injected WS-CoQ10 fed group; H between paraquat injected placebo fed group and paraquat injected WS-CoQ10 fed group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2724477&req=5

Figure 3: Oxidative stress markers. Experiment 2: Following behavioral testing, rats were sacrificed, midbrain tissue was homogenized and assayed for GSH (A) and MDA levels (B). Data (mean ± SEM) was normalized to that of saline injected placebo fed group, which was taken as 100%. (A) statistically significant differences (p < .001): *** between saline injected placebo fed group and paraquat injected placebo fed group; ### between paraquat injected placebo fed group and saline injected WS-CoQ10 fed group; HHH between paraquat injected placebo fed group and paraquat injected WS-CoQ10 fed group. (B) Statistically significant differences (p < .05): * between saline injected placebo fed group and paraquat injected placebo fed group; # between paraquat injected placebo fed group and saline injected WS-CoQ10 fed group; H between paraquat injected placebo fed group and paraquat injected WS-CoQ10 fed group.
Mentions: We measured the GSH content (Figure 3A) and lipid peroxidation (Figure 3B) in the midbrain of experimental animals as the markers of oxidative stress. We compared the levels of these markers in the brains of PQ-injected groups (Placebo and WS-CoQ10 fed groups) with the saline injected groups (Placebo and WS-CoQ10 fed groups).

Bottom Line: Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD.Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies.This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada. somayaj@uwindsor.ca

ABSTRACT

Background: Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance.

Results: Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod) evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats.

Conclusion: Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

Show MeSH
Related in: MedlinePlus