Pre- or post-treatment with the mitochondrial uncoupler 2,4-dinitrophenol attenuates striatal quinolinate lesions.
We have examined the neuroprotective efficacy of the mitochondrial uncoupler 2,4-dinitrophenol (DNP) in animals receiving striatal injections of the neurotoxin quinolinic acid. Animals administered DNP either 1 h before or 3 h following QA infusion developed lesions that were 25% smaller than control animals. Animals treated with the DNP analogue 2,4,6-trinitrophenol, which does not possess uncoupling activity in intact mitochondria, showed no neuroprotection. These results indicate that DNP, and other compounds that diminish the mitochondrial membrane potential, might provide a novel approach to the treatment of acute neurological injury.
Maragos
William F
WF
Department of Neurology, University of Kentucky Medical Center, Kentucky Clinic, Rm. L-445, Lexington, KY 40536-0284, USA.
Rockich
Kevin T
KT
Dean
Jesse J
JJ
Young
Kristie L
KL
D019297:2,4-Dinitrophenol / Q000031:analogs & derivatives / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D010851:Picrates / Q000494:pharmacology; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014475:Uncoupling Agents / Q000494:pharmacology*
D010851:Picrates; D014475:Uncoupling Agents; C005858:picric acid; D017378:Quinolinic Acid; D019297:2,4-Dinitrophenol