Promethazine protects against 3-nitropropionic acid-induced neurotoxicity.
Promethazine (PMZ), an FDA-approved antihistaminergic drug, was identified as a potentially neuroprotective compound in a NINDS screening program. It was shown to protect against ischemia in mice, to delay disease onset in a mouse model of amyotrophic lateral sclerosis and to inhibit Ca(2+)-induced mitochondrial permeability transition in rat liver mitochondria. We investigated whether PMZ could protect against the neurotoxic effects induced by 3-nitropropionic acid (3-NP), an inhibitor of the succinate dehydrogenase, used to model Huntington's disease (HD) in rats. Lewis rats receiving chronic subcutaneous infusion of 3-NP were treated with PMZ. The findings indicate that chronic PMZ treatment significantly reduced 3-NP-induced striatal lesion volume, loss of GABAergic neurons and number of apoptotic cells in the striatum. PMZ showed a strong neuroprotective effect against 3-NP toxicity in vivo.
Cleren
Carine
C
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY 10065, USA. carine.cleren@unice.fr
Calingasan
Noel Y
NY
Starkov
Anatoly
A
Jacquard
Carine
C
Chen
Junya
J
Brouillet
Emmanuel
E
Beal
M Flint
MF
D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D002545:Brain Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D004195:Disease Models, Animal; D006816:Huntington Disease / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds / Q000633:toxicity*; D011398:Promethazine / Q000494:pharmacology*; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D011917:Rats, Inbred Lew; D013385:Succinate Dehydrogenase / Q000378:metabolism
D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D013385:Succinate Dehydrogenase; D011398:Promethazine; C015392:3-nitropropionic acid