Role of Mitochondrial Mechanism in Chemotherapy-Induced Peripheral Neuropathy

Waseem, Mohammad; Kaushik, Pooja; Tabassum, Heena; Parvez, Suhel

doi:10.2174/1389200219666171207121313

Cited by 45 publications

(32 citation statements)

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“…It is important to speculate that OXAL-induced stimulation of MEP-induced channels presented herein contributes to its activation of mitochondrial permeability transition pore. Our results are in parallel with a scenario showing the role of mitochondrial mechanism in platinum-induced peripheral neuropathy [55,56]. It remains to be studied to what extent the presence of OXAL can enhance MEP-elicited channels which indirectly activate the intrinsic pathway to apoptotic or necrotic changes by inducing change in mitochondrial permeability transition pore.…”

Section: Discussionsupporting

confidence: 82%

Characterization in Dual Activation by Oxaliplatin, a Platinum-Based Chemotherapeutic Agent of Hyperpolarization-Activated Cation and Electroporation-Induced Currents

Chang

Gao

et al. 2020

IJMS

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Oxaliplatin (OXAL) is regarded as a platinum-based anti-neoplastic agent. However, its perturbations on membrane ionic currents in neurons and neuroendocrine or endocrine cells are largely unclear, though peripheral neuropathy has been noted during its long-term administration. In this study, we investigated how the presence of OXAL and other related compounds can interact with two types of inward currents; namely, hyperpolarization-activated cation current (Ih) and membrane electroporation-induced current (IMEP). OXAL increased the amplitude or activation rate constant of Ih in a concentration-dependent manner with effective EC50 or KD values of 3.2 or 6.4 μM, respectively, in pituitary GH3 cells. The stimulation by this agent of Ih could be attenuated by subsequent addition of ivabradine, protopine, or dexmedetomidine. Cell exposure to OXAL (3 μM) resulted in an approximately 11 mV rightward shift in Ih activation along the voltage axis with minimal changes in the gating charge of the curve. The exposure to OXAL also effected an elevation in area of the voltage-dependent hysteresis elicited by long-lasting triangular ramp. Additionally, its application resulted in an increase in the amplitude of IMEP elicited by large hyperpolarization in GH3 cells with an EC50 value of 1.3 μM. However, in the continued presence of OXAL, further addition of ivabradine, protopine, or dexmedetomidine always resulted in failure to attenuate the OXAL-induced increase of IMEP amplitude effectively. Averaged current-voltage relation of membrane electroporation-induced current (IMEP) was altered in the presence of OXAL. In pituitary R1220 cells, OXAL-stimulated Ih remained effective. In Rolf B1.T olfactory sensory neurons, this agent was also observed to increase IMEP in a concentration-dependent manner. In light of the findings from this study, OXAL-mediated increases of Ih and IMEP may coincide and then synergistically act to increase the amplitude of inward currents, raising the membrane excitability of electrically excitable cells, if similar in vivo findings occur.

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Section: Discussionsupporting

confidence: 82%

Characterization in Dual Activation by Oxaliplatin, a Platinum-Based Chemotherapeutic Agent of Hyperpolarization-Activated Cation and Electroporation-Induced Currents

Chang

Gao

et al. 2020

IJMS

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“…Previous studies have shown the important role of oxidative stress in the toxicity of oxaliplatin [ 11 , 37 , 51 – 53 ]. An excessive production of ROS can alter endothelial cells integrity by cytoskeletal rearrangements and redistribution of TJ proteins, triggering a loss of cellular interaction and increasing their permeability [ 54 – 57 ].…”

Section: Discussionmentioning

confidence: 99%

Oxaliplatin-induced blood brain barrier loosening: a new point of view on chemotherapy-induced neurotoxicity

et al. 2018

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Oxaliplatin is a key drug in the treatment of advanced metastatic colorectal cancer. Despite its beneficial effects in tumor reduction, the most prevalent side-effect of oxaliplatin treatment is a chemotherapy-induced neuropathy that frequently forces to discontinue the therapy. Indeed, along with direct damage to peripheral nerves, the chemotherapy-related neurotoxicity involves also the central nervous system (CNS) as demonstrated by pain chronicity and cognitive impairment (also known as chemobrain), a newly described pharmacological side effect.The presence of the blood brain barrier (BBB) is instrumental in preventing the entry of the drug into the CNS; here we tested the hypothesis that oxaliplatin might enter the endothelial cells of the BBB vessels and trigger a signaling pathway that induce the disassembly of the tight junctions, the critical components of the BBB integrity.By using a rat brain endothelial cell line (RBE4) we investigated the signaling pathway that ensued the entry of oxaliplatin within the cell. We found that the administration of 10 μM oxaliplatin for 8 and 16 h induced alterations of the tight junction (TJs) proteins zonula occludens-1 (ZO-1) and of F-actin, thus highlighting BBB alteration. Furthermore, we reported that intracellular oxaliplatin rapidly induced increased levels of reactive oxygen species and endoplasmic reticulum stress, assessed by the evaluation of glucose-regulated protein GRP78 expression levels. These events were accompanied by activation of caspase-3 that led to extracellular ATP release.These findings suggested a possible novel mechanism of action for oxaliplatin toxicity that could explain, at least in part, the chemotherapy-related central effects.

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“…Numerous studies with cycling cells in cell culture and cisplatin were done in the past; the toxic effects of cisplatin on cells were associated with the formation of platinum-DNA adducts as well as damage to other cellular components and organelles—from mitochondria to axonal transport (Avan et al 2015 ; Boyette-Davis et al 2015 ; Canta et al 2015 ; Carozzi et al 2015 ; Chiorazzi et al 2015 ; Foufelle and Fromenty 2016 ; Kanat et al 2017 ; Kerckhove et al 2017 ; McDonald et al 2005 ; Nicolini et al 2015 ; Starobova and Vetter 2017 ; Waseem et al 2018 ). In order to investigate the subcellular location of platinum in cisplatin-exposed NT2-N cells, we chose to use X-ray fluorescence microscopy (XFM)—the only imaging technique that can be used for direct visualization and quantification od chemical elements, native to cells or exogenously introduced into them (Bourassa et al 2014 ; Kim et al 2010 ; Paunesku et al 2006 , 2012 ; Wang et al 2014 ; Weekley et al 2013 ; Wolford et al 2010 ).…”

Section: Resultsmentioning

confidence: 99%

“…The effects of cisplatin on living cells are generally considered to be associated with genomic and mitochondrial DNA damage and the creation of DNA adducts (Chiorazzi et al 2015 ; Johnstone et al 2016 ; Kanat et al 2017 ; Starobova and Vetter 2017 ; Wang and Lippard 2005 ) but its side-effects are often associated with oxidative stress (Mercantepe et al 2018 ; Wang et al 2018 ). Oxidative stress, nitro-oxidative stress and mitochondrial impairment are often noted as possible factors in the etiology of cisplatin-induced neuronal injury (Areti et al 2014 ; Carozzi et al 2010 ; Ma et al 2018 ; Maj et al 2017 ; Waseem et al 2018 ). Many different agents have been tested as possible interventions (Albers et al 2014 ; Avan et al 2015 ; Freyer et al 2017 ; Fu et al 2017 ; Glimelius et al 2018 ; Kerckhove et al 2017 ; Mishra and Alsbeih 2017 ; Piccolo and Kolesar 2014 ; Schloss et al 2013 ), but a clear view of their mechanism of action is still lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Neuropathy caused by platinum drugs is associated not only with the formation of DNA adducts in genomic and mitochondrial DNA (Chiorazzi et al 2015 ; Kanat et al 2017 ; Starobova and Vetter 2017 ) but also with production of reactive oxygen and nitrogen species with consequent mitochondrial and endoplasmic reticulum stress and changes in axonal transport, etc. (Avan et al 2015 ; Boyette-Davis et al 2015 ; Canta et al 2015 ; Carozzi et al 2015 ; Chiorazzi et al 2015 ; Foufelle and Fromenty 2016 ; Kanat et al 2017 ; Kerckhove et al 2017 ; McDonald et al 2005 ; Nicolini et al 2015 ; Waseem et al 2018 ). For that reason, many treatments against CIPN include different types of antioxidants (Areti et al 2014 ; Carozzi et al 2010 ; Ma et al 2018 ; Wang et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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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.

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Role of Mitochondrial Mechanism in Chemotherapy-Induced Peripheral Neuropathy

Cited by 45 publications

References 0 publications

Characterization in Dual Activation by Oxaliplatin, a Platinum-Based Chemotherapeutic Agent of Hyperpolarization-Activated Cation and Electroporation-Induced Currents

Characterization in Dual Activation by Oxaliplatin, a Platinum-Based Chemotherapeutic Agent of Hyperpolarization-Activated Cation and Electroporation-Induced Currents

Oxaliplatin-induced blood brain barrier loosening: a new point of view on chemotherapy-induced neurotoxicity

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

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