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.
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.


CONCLUSIONS
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.
Somayajulu-Niţu
Mallika
M
Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada. somayaj@uwindsor.ca
Sandhu
Jagdeep K
JK
Cohen
Jerome
J
Sikorska
Marianna
M
Sridhar
T S
TS
Matei
Anca
A
Borowy-Borowski
Henryk
H
Pandey
Siyaram
S
D000818:Animals; D016923:Cell Death; D007150:Immunohistochemistry; D008124:Locomotion; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D010269:Paraquat / Q000506:poisoning*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans; D045442:Rotarod Performance Test; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use*
D014815:Vitamins; D014451:Ubiquinone; D014446:Tyrosine 3-Monooxygenase; C024989:coenzyme Q10; D010269:Paraquat