Protective effect of minocycline, a semi-synthetic second-generation tetracycline against 3-nitropropionic acid (3-NP)-induced neurotoxicity.
3-Nitropropionic acid (3-NP) is an irreversible inhibitor of the electron transport enzyme succinate dehydrogenase, a mitochondrial Complex II enzyme. Minocycline is a semi-synthetic second-generation tetracycline with neuroprotective activity and has the capability to effectively cross the blood-brain barrier. We investigated the effects of minocycline on behavioral, biochemical, inflammation related and neurochemical alterations induced by the sub-chronic administration of 3-nitropropionic acid to rats. Chronic pre-administration of minocycline (50 and 100mg/kg) dose dependently prevented 3-NP-induced dysfunction behavioral (hypoactivity, memory retention, locomotor and rota-rod activity). In addition, 3-NP produced a marked increase in lipid peroxidation levels whereas decreased the activities of catalase and succinate dehydrogenase. In contrast, pretreatment of 3-NP injected rats with minocycline resulted in the attenuation of all these alterations. A marked increase in an inflammatory cytokine TNF-alpha by 3-NP was also decreased by minocycline treatment. Neurochemically, the administration of 3-NP significantly decreased the levels of catecholamines in the brain homogenates (dopamine, norepinephrine and serotonin) which were reversed by pretreatment of minocycline. The present finding explains the neuroprotective effect of minocycline against 3-NP toxicity by virtue of its antioxidant and anti-inflammatory activity.
Ahuja
Manuj
M
Pharmacology Division, University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh 160014, India.
Bishnoi
Mahendra
M
Chopra
Kanwaljit
K
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008911:Minocycline / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D018696:Neuroprotective Agents; D020258:Neurotoxicity Syndromes / Q000517:prevention & control* / Q000523:psychology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009574:Nitro Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004856:Postural Balance / Q000187:drug effects; D011422:Propionates / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D009574:Nitro Compounds; D011422:Propionates; D013385:Succinate Dehydrogenase; D008911:Minocycline; C015392:3-nitropropionic acid