Research on an in vitro cell system for testing the neurotoxicity of kynurenine pathway metabolites

Riferimento: 
Pharmazie. 2011 Nov;66(11):899-903.
Autori: 
Wszelaki N, Melzig MF.
Fonte: 
Pharmazie. 2011 Nov;66(11):899-903.
Anno: 
2011
Azione: 
Al fine di alterare la risposta cellulare alle neurotossine, il fattore di necrosi tumorale alfa e l'acido retinoico (RA) sono stati utilizzati come agenti differenzianti nelle linee cellulari del neuroblastoma umano.
Target: 
Fattore di necrosi tumorale alfa – RA/neuroblastoma.

ABSTRACT
Quinolinic acid (QUIN), kynurenine acid (KYNA) and 3-hydroxykynurenine (3-HK) - metabolites of the kynurenine pathway are considered to be associated with many central nervous system diseases. However, in neuroscience research in order to test neurotoxicity or neuroprotection against these compounds only primary cell models are available. In this investigation we aimed to develop a simple, rapid and accurate cellular in vitro model using immortalized human neuroblastoma cell lines, namely SK-N-SH and SH-SY5Y differentiated by treatment with various agents. In order to alter the cell response to the neurotoxins, tumor necrosis factor-alpha and retinoic acid (RA) as differentiating agents and modulation of the cellular metabolism through changing the sugar composition from galactose to glucose in media were used. Our results indicated that although RA-differentiation of both cell lines induced the expression of neuronal features, cell vulnerability after exposure to control neurotoxicants (salsolinol, 6-hydroxydopamine) and 3-HK was decreased in comparison to untreated cells and was not influenced after exposure to QUIN and KYNA. Interestingly, the same observations were done in cells grown in galactose containing media.

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