The role of oxidative stress in paraquat-induced neurotoxicity in rats: protection by non peptidyl superoxide dismutase mimetic.
Herbicides, including paraquat, may produce neurodegenerative effect when given both peripherally and into the brain though the pathophysiological mechanism is still unknown. Microinfusion of paraquat into the Substantia Nigra (50 microg) produced increased motor activity, jumping and circling opposite to the injection site, associated with ECoG desynchronization, high voltage epileptogenic spikes, and with neuropathological effects. These effects were accompanied by increase of malondialdehyde (MDA) levels in the Substantia Nigra, suggesting that paraquat was able to induce oxidative stress when injected directly into the rat brain. Pre-treatment of rats with M40401, a non peptidyl superoxide dismutase (SOD) mimetic given directly into the Substantia Nigra or i.p. prevented both behavioural, electrocorticogram and neuropathological effects and MDA elevation. Taken together, these results demonstrate that paraquat produces brain damage via abnormal formation of oxygen free radicals and that this effect may be counteracted by novel SOD mimetics.
Mollace
Vincenzo
V
Department of Pharmacobiological Sciences, University of Catanzaro Magna Graecia, Complesso Niní Barbieri-88021, Roccelletta di Borgia (CZ), Italy. mollace@libero.it
Iannone
Michelangelo
M
Muscoli
Carolina
C
Palma
Emesto
E
Granato
Teresa
T
Rispoli
Vincenzo
V
Nisticò
Robert
R
Rotiroti
Domenicantonio
D
Salvemini
Daniela
D
D000818:Animals; D004562:Electrocardiography / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced / Q000517:prevention & control; D005609:Free Radicals / Q000378:metabolism; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000494:pharmacology
D005609:Free Radicals; D006540:Herbicides; C426066:M40401; D018696:Neuroprotective Agents; D009942:Organometallic Compounds; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D010269:Paraquat