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Coenzyme Q10 and nicotinamide and a free radical spin trap protect against MPTP neurotoxicity
J B Schulz1, D R Henshaw, R T Matthews
1Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114, USA.
Abstract:
1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) produces Parkinsonism in both experimental animals and in man. MPTP is metabolized to 1-methyl-4-phenylpridinium, an inhibitor of mitochondrial complex I. MPTP administration produces ATP depletions in vivo, which may lead to secondary excitotoxicity and free radical generation. If this is the case then agents which improve mitochondrial function or free radical scavengers should attenuate MPTP neurotoxicity. In the present experiments three regimens of MPTP administration produced varying degrees of striatal dopamine depletion. A combination of coenzyme Q10 and nicotinamide protected against both mild and moderate depletion of dopamine. In the MPTP regimen which produced mild dopamine depletion nicotinamide or the free radical spin trap N-tert-butyl-alpha-(2-sulfophenyl)-nitrone were also effective. There was no protection with a MPTP regimen which produced severe dopamine depletion. These results show that agents which improve mitochondrial energy production (coenzyme Q10 and nicotinamide) and free radical scavengers can attenuate mild to moderate MPTP neurotoxicity.
Insights
Agents like coenzyme Q10 and nicotinamide can protect against mild to moderate Parkinsonism caused by 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) by improving mitochondrial function and scavenging free radicals.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) induces Parkinsonism in humans and animals.
- MPTP is metabolized to 1-methyl-4-phenylpridinium, inhibiting mitochondrial complex I and causing ATP depletion.
- This ATP depletion may lead to excitotoxicity and free radical generation, suggesting potential therapeutic targets.
Purpose of the Study:
- To investigate if agents improving mitochondrial function or scavenging free radicals can attenuate MPTP-induced neurotoxicity.
- To evaluate the protective effects of coenzyme Q10, nicotinamide, and a spin trap against MPTP neurotoxicity.
Main Methods:
- MPTP was administered using three different regimens to induce varying degrees of striatal dopamine depletion.
- Mice were treated with coenzyme Q10, nicotinamide, or N-tert-butyl-alpha-(2-sulfophenyl)-nitrone.
- Striatal dopamine levels were measured to assess neurotoxicity and the efficacy of protective agents.
Main Results:
- A combination of coenzyme Q10 and nicotinamide protected against mild and moderate dopamine depletion.
- Nicotinamide or the spin trap N-tert-butyl-alpha-(2-sulfophenyl)-nitrone also showed protection in cases of mild dopamine depletion.
- No protection was observed when MPTP administration resulted in severe dopamine depletion.
Conclusions:
- Agents that enhance mitochondrial energy production, such as coenzyme Q10 and nicotinamide, can attenuate mild to moderate MPTP neurotoxicity.
- Free radical scavengers may also offer protection against MPTP-induced neurotoxicity.
- The efficacy of these agents is dependent on the severity of MPTP-induced neurotoxicity.