1-Methyl-4-phenylpyridine (MPP+) induces oxidative stress in the rodent

• Published in: Life sciences (1973) Vol. 38; no. 8; p. 743
• Main Authors: Johannessen, J N, Adams, J D, Schuller, H M, Bacon, J P, Markey, S P
• Format: Journal Article
• Language: English
• Published: Netherlands 24.02.1986
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 1-Methyl-4-phenylpyridinium; Animals; Chemical and Drug Induced Liver Injury; Edema; Female; Glutathione - blood; Kidney Diseases - chemically induced; Kidney Diseases - pathology; Kinetics; Liver Diseases - pathology; Lung Diseases - chemically induced; Lung Diseases - pathology; Male; Mice; Mice, Inbred C57BL; Oxidation-Reduction; Pyridines - metabolism; Pyridines - toxicity; Pyridinium Compounds - metabolism; Pyridinium Compounds - toxicity; Rats; Rats, Inbred Strains; Selenium - deficiency
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(86)90589-8

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) produces an irreversible parkinsonism in primates. Recent evidence suggests metabolism of MPTP to 1-methyl-4-phenylpyridine (MPP+) is required for toxicity. We have proposed that MPP+ may play a central role in the toxicity of MPTP, but direct assessment of the effects of MPP+ in brain is difficult. Therefore, we have sought to define the mechanism of peripheral MPP+ toxicity in the rat and mouse. Systemically administered MPP+ produced its major pathology in the lung and was typified by perivascular edema. An increase in plasma glutathione disulfide concentrations also resulted, suggesting that MPP+ in analogy to paraquat produces oxidative stress. In addition, the lethality of MPP+ in the mouse was increased by dietary selenium deficiency. These results define in both pathological and chemical terms the potent systemic toxicity of MPP+ and suggest that MPP+, because of its high concentration in primate brain, has the potential to play an important role in the CNS toxicity of MPTP.