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Neurotoxicity and apoptosis induced by pyrroloquinoline quinone and its ester derivative on primary cortical neurons

Ying Peng, Dong Xu, Shishi Mao, Xingqin Zhou
Neurotoxicology 2020 February 14
32068067
Pyrroloquinoline quinone (PQQ) and its esterified derivative, PQQ ester (PQQE), have potential to treat or diagnose neurological and psychological disorders. However, their neurotoxicity remains unclear. To provide reference data for the brain targeting drug delivery techniques, the cytotoxic effects of PQQ and PQQE were examined in primary mouse cortical neurons. The results indicated that both PQQ and PQQE decreased neuron viability, reduced intracellular ATP level and disrupted the mitochondrial membrane potential in a concentration- and time-dependent manner, while PQQ was less potent than PQQE. PQQ and PQQE induced apoptosis involving increase of Bax, decrease of Bcl-2, release of mitochondrial cytochrome C into the cytosol, activation of caspase-3 and cleavage of PARP. A single mouse intracephalic injection of PQQ or PQQE showed similar results. Based on these findings, high-concentration PQQ or PQQE treatment could induce a wide range of neurotoxicity and apoptosis. The lowest observed adverse effect levels (LOAELs) of PQQ and PQQE were 10 µM and 2 µM respectively and the no observed adverse effect levels (NOAELs) were 5 µM and 1 µM respectively in mice cortical neurons.

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