2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Is Selectively Toxic to Primary Dopaminergic Neurons In Vitro

• DOI: 10.1093/toxsci/kfu060
• Publication Date: 2014-04-10T06:07:28Z
• Authors: Amy M. Griggs; Zeynep S. Agim; Vartika R. Mishra; Mitali A. Tambe; Alison E. Directo...; Kenneth W. Turtel...; George P. McCabe; Jean-Christophe R...; Jason R. Cannon
• Keywords: Neurotoxicity; Heterocyclic amine; Neurotoxin

Parkinson's disease (PD) is the second most common neurodegenerative disease. Much data has linked etiology of PD to a variety environmental factors. The majority cases are thought arise from combination genetic susceptibility and Chronic exposures dietary factors, including meat, have been identified as potential risk Although heterocyclic amines that produced during high-temperature meat cooking known be carcinogenic, their effect on nervous system yet studied in depth. In this study, we investigated neurotoxic effects 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), highly abundant amine cooked vitro. We tested toxicity PhIP two major phase I metabolites, N-OH-PhIP 4'-OH-PhIP, using primary mesencephalic cultures rat embryos. This culture contains both dopaminergic nondopaminergic neurons, which allows specificity neurotoxicity readily examined. find exposure or selectively toxic neurons cultures, resulting decreased percentage neurons. Neurite length surviving Exposure 4'-OH-PhIP did not produce significant neurotoxicity. treatment also increased formation oxidative damage markers, 4-hydroxy-2-nonenal (HNE) 3-nitrotyrosine Pretreatment with N-acetylcysteine was protective. Finally, blueberry extract, factor antioxidant other protective mechanisms, prevented PhIP-induced toxicity. Collectively, our study suggests, for first time, likely through inducing stress.