Chemotherapy-induced peripheral neurotoxicity (CIPN) is a side effect limiting cisplatin (CDDP) and docetaxel (DOCE) treatment. Erythropoietin (EPO) is a hematopoietic growth factor also displaying neurotrophic properties. Evidence suggests that EPO's neuroprotective action may rely on PI3K/AKT pathway activation; however, data regarding the EPO neuroprotective mechanism are still limited. This study evaluated the effect of EPO on organotypic cultures of rat dorsal root ganglia (DRG) and in primary cultures of DRG-dissociated sensory neurons exposed to CDDP- and DOCE-induced neurotoxicity, aiming to investigate EPO's neuroprotective mechanism. Subsequently, the levels of AKT expression and activation were analyzed by Western blot in neurons exposed to CDDP or DOCE; AKT's role was further evaluated by using a chemical inhibitor of AKT activation, wortmannin. In these models EPO, was protective against both CDDP- and DOCE-induced cell death and against CDDP-induced neurite elongation reduction. A modulation of AKT activation was observed in CDDP-treated neurons, and the presence of wortmannin prevented EPO's neuroprotective action against CDDP toxicity but did not have any effect on EPO's protection against DOCE-induced toxicity, thus ruling out the PI3K-AKT pathway as the mechanism of EPO's effect in neuronal death prevention after DOCE exposure. Our results confirm in vitro the effectiveness of EPO as a neuroprotectant against both CDDP- and DOCE-induced neurotoxicity. In addition, a role of PI3K/AKT in EPO's protection against CDDP, but not against DOCE, neurotoxicity was shown, suggesting that alternative pathways could be involved in EPO's neuroprotective activity. (

Maggioni, D., Nicolini, G., Chiorazzi, A., Meregalli, C., Cavaletti, G., Tredici, G. (2010). Different effects of erythropoietin in cisplatin- and docetaxel-induced neurotoxicity: An in vitro study. JOURNAL OF NEUROSCIENCE RESEARCH, 88(14), 3171-3179 [10.1002/jnr.22465].

Different effects of erythropoietin in cisplatin- and docetaxel-induced neurotoxicity: An in vitro study

MAGGIONI, DANIELE
Primo
;
NICOLINI, GABRIELLA
Secondo
;
CHIORAZZI, ALESSIA;MEREGALLI, CRISTINA;CAVALETTI, GUIDO ANGELO
Penultimo
;
TREDICI, GIOVANNI
Ultimo
2010

Abstract

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a side effect limiting cisplatin (CDDP) and docetaxel (DOCE) treatment. Erythropoietin (EPO) is a hematopoietic growth factor also displaying neurotrophic properties. Evidence suggests that EPO's neuroprotective action may rely on PI3K/AKT pathway activation; however, data regarding the EPO neuroprotective mechanism are still limited. This study evaluated the effect of EPO on organotypic cultures of rat dorsal root ganglia (DRG) and in primary cultures of DRG-dissociated sensory neurons exposed to CDDP- and DOCE-induced neurotoxicity, aiming to investigate EPO's neuroprotective mechanism. Subsequently, the levels of AKT expression and activation were analyzed by Western blot in neurons exposed to CDDP or DOCE; AKT's role was further evaluated by using a chemical inhibitor of AKT activation, wortmannin. In these models EPO, was protective against both CDDP- and DOCE-induced cell death and against CDDP-induced neurite elongation reduction. A modulation of AKT activation was observed in CDDP-treated neurons, and the presence of wortmannin prevented EPO's neuroprotective action against CDDP toxicity but did not have any effect on EPO's protection against DOCE-induced toxicity, thus ruling out the PI3K-AKT pathway as the mechanism of EPO's effect in neuronal death prevention after DOCE exposure. Our results confirm in vitro the effectiveness of EPO as a neuroprotectant against both CDDP- and DOCE-induced neurotoxicity. In addition, a role of PI3K/AKT in EPO's protection against CDDP, but not against DOCE, neurotoxicity was shown, suggesting that alternative pathways could be involved in EPO's neuroprotective activity. (
Articolo in rivista - Articolo scientifico
erythropoietin;cisplatin;docetaxel;peripheral neurotoxicity;PI3K-AKT
English
2010
88
14
3171
3179
none
Maggioni, D., Nicolini, G., Chiorazzi, A., Meregalli, C., Cavaletti, G., Tredici, G. (2010). Different effects of erythropoietin in cisplatin- and docetaxel-induced neurotoxicity: An in vitro study. JOURNAL OF NEUROSCIENCE RESEARCH, 88(14), 3171-3179 [10.1002/jnr.22465].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/16436
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