Neuroprotective Role of Selected Antioxidant Agents in Preventing Cisplatin-Induced Damage of Human Neurons In Vitro

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of platinum-based chemotherapy and decreases the quality of life of cancer patients. We compared neuroprotective properties of several agents using an in vitro model of terminally differentiated human cells NT2-N derived from cell line NT2/D1. Sodium azide and an active metabolite of amifostine (WR1065) increase cell viability in simultaneous treatment with cisplatin. In addition, WR1065 protects the non-dividing neurons by decreasing cisplatin caused oxidative stress and apoptosis. Accumulation of Pt in cisplatin-treated cells was heterogeneous, but the frequency and concentration of Pt in cells were lowered in the presence of WR1065 as shown by X-ray fluorescence microscopy (XFM). Transition metals accumulation accompanied Pt increase in cells; this effect was equally diminished in the presence of WR1065. To analyze possible chemical modulation of Pt-DNA bonds, we examined the platinum L III near edge spectrum by X-ray absorption spectroscopy. The spectrum found in cisplatin-DNA samples is altered differently by the addition of either WR1065 or sodium azide. Importantly, a similar change in Pt edge spectra was noted in cells treated with cisplatin and WR1065. Therefore, amifostine should be reconsidered as a candidate for treatments that reduce or prevent CIPN. Electronic supplementary material The online version of this article (10.1007/s10571-019-00667-7) contains supplementary material, which is available to authorized users.

Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms

“…Amifostine was also tested for prevention of CIPN, because one of its active metabolites, WR1065, has been demonstrated to protect differentiated neurons from cisplatin-induced damage [ 98 ]. This thiol accumulates in normal tissues more than in tumors, protecting them from side effects of radiation and chemotherapy without decreasing their therapeutic efficacy [ 177 ].…”

The role of ginseng derivatives against chemotherapy-induced cardiotoxicity: A systematic review of non-clinical studies

“…Various studies have shown, patients treated with chemotherapy have a lower capacity for anti-oxidant ( 22 , 23 ). Therefore, it is assumed using some material such as ginseng and its derivatives, which have anti-oxidant properties can reduce the production of free radicals.…”

Pregabalin protected cisplatin-induced oxidative neurotoxicity in neuronal cell line

“…CSP kills the tumor cells through activation or inhibition of several molecular pathways, including excessive production of reactive oxygen species (ROS) and overload entry of Ca 2+ (Nazıroğlu and Braidy 2017;Xie et al, 2018). However, there is adverse effect CSP in neurons through the imbalance between CSP and excessive oxidative stressinduced overload calcium ion (Ca 2+ ) entry, although the adverse effects of CSP were treated by antioxidants (Piccolini et al 2013;Chen et al 2019;Popović et al 2019).…”