Preventing oxaliplatin-induced peripheral neuropathy with a Pt(IV)-Mn(II) prodrug: Toxicity, behavioral and X-ray fluorescence microscopy studies
Abstract
Although widely used in chemotherapeutic treatments, platinum (Pt)-based drugs -namely cisplatin (Cis), oxaliplatin (Ox), and carboplatin- encounter several drawbacks that significantly limit their clinically applicable doses, such as the development of various side effects. These toxicities, including nephrotoxicity and neurotoxicity associated with Cis and Ox, respectively, arise from the lack of selectivity of these drugs toward cancer cells. While numerous alternative treatments -some employing a Pt(IV) prodrug strategy- have been investigated in preclinical settings for their anticancer activity, studies evaluating their systemic toxicities remain scarce. However, assessing these toxicities is crucial for the development of improved therapies. This study aimed to evaluate the systemic toxicities induced by PtC5Mn, a novel Pt(IV)-Mn(II) prodrug reported to exhibit anticancer activity in both in vitro and in vivo models of colorectal cancer, as well as Mn1C5, its corresponding Mn(II) complex that mimics superoxide dismutase (SOD) activity, in combination with Ox. Additionally, their potential protective effects against Ox-induced peripheral neuropathy were explored through behavioral studies and mapping of Pt localization in sciatic nerves sections by Synchrotron-based Scanning X-Ray Fluorescence microscopy. Our results support the use of Pt(IV) prodrugs and redox modulation by SOD mimics for the mitigation of oxaliplatin-associated off-target effects.
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BibTeX
@article{lopezsanchez2026preventing,
title = {{Preventing oxaliplatin-induced peripheral neuropathy with a Pt(IV)-Mn(II) prodrug: Toxicity, behavioral and X-ray fluorescence microscopy studies}},
author = {Alvaro Lopez-Sanchez and Ram Pravin Kumar Muthuramalingam and Marine Thomas and Kadda Medjoubi and Alice Balfourier and Christine Rampon and Clotilde Policar and Andrea Somogyi and Giulia Adriani and Frédéric Batteux and Carole Nicco and Giorgia Pastorin and Romain Coriat and Hélène C Bertrand},
journal = {Biomedicine and Pharmacotherapy},
year = {2026},
month = oct,
doi = {10.1016/j.biopha.2026.120008},
url = {https://hal.science/hal-05838934v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Preventing oxaliplatin-induced peripheral neuropathy with a Pt(IV)-Mn(II) prodrug: Toxicity, behavioral and X-ray fluorescence microscopy studies
AU - Alvaro Lopez-Sanchez
AU - Ram Pravin Kumar Muthuramalingam
AU - Marine Thomas
AU - Kadda Medjoubi
AU - Alice Balfourier
AU - Christine Rampon
AU - Clotilde Policar
AU - Andrea Somogyi
AU - Giulia Adriani
AU - Frédéric Batteux
AU - Carole Nicco
AU - Giorgia Pastorin
AU - Romain Coriat
AU - Hélène C Bertrand
PY - 2026
DA - 2026/10/24
JO - Biomedicine and Pharmacotherapy
DO - 10.1016/j.biopha.2026.120008
UR - https://hal.science/hal-05838934v1
AB - Although widely used in chemotherapeutic treatments, platinum (Pt)-based drugs -namely cisplatin (Cis), oxaliplatin (Ox), and carboplatin- encounter several drawbacks that significantly limit their clinically applicable doses, such as the development of various side effects. These toxicities, including nephrotoxicity and neurotoxicity associated with Cis and Ox, respectively, arise from the lack of selectivity of these drugs toward cancer cells. While numerous alternative treatments -some employing a Pt(IV) prodrug strategy- have been investigated in preclinical settings for their anticancer activity, studies evaluating their systemic toxicities remain scarce. However, assessing these toxicities is crucial for the development of improved therapies. This study aimed to evaluate the systemic toxicities induced by PtC5Mn, a novel Pt(IV)-Mn(II) prodrug reported to exhibit anticancer activity in both in vitro and in vivo models of colorectal cancer, as well as Mn1C5, its corresponding Mn(II) complex that mimics superoxide dismutase (SOD) activity, in combination with Ox. Additionally, their potential protective effects against Ox-induced peripheral neuropathy were explored through behavioral studies and mapping of Pt localization in sciatic nerves sections by Synchrotron-based Scanning X-Ray Fluorescence microscopy. Our results support the use of Pt(IV) prodrugs and redox modulation by SOD mimics for the mitigation of oxaliplatin-associated off-target effects.
SN - 0753-3322
SN - 1950-6007
ER -