A possible link of oxaliplatin‐induced neuropathy with potassium channel deficit

Dimitrov, Alexander G.; Dimitrova, Nonna A.

doi:10.1002/mus.22311

Cited by 22 publications

(19 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro studies of various vertebrate nerves showed that dysfunction of voltage-gated potassium and/or sodium channels is involved in oxaliplatin-induced axonal hyperexcitability (7). Thus, the channels involved in the neuropathy secondary to oxaliplatin treatment had been ill defined until recent reports clearly implicated the voltage-gated potassium channels as targets of oxaliplatin, offering new insights into the pharmacological prevention of peripheral neuropathy (24)(25)(26)(27). Our mouse model not only confirms the electrophysiological changes in potassium channels, but to the best of our knowledge, also demonstrates for the first time the therapeutic effect of mangafodipir.…”

Section: Discussionmentioning

confidence: 99%

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Coriat¹,

Alexandre²,

Nicco³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

Background. The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity. Because this neurotoxicity involves ROS production, we investigated the efficacy of mangafodipir, a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer.Methods. The effects of mangafodipir were examined in mice following treatment with oxaliplatin. Neurotoxicity, axon myelination, and advanced oxidized protein products (AOPPs) were monitored. In addition, we enrolled 23 cancer patients with grade ≥2 oxaliplatin-induced neuropathy in a phase II study, with 22 patients receiving i.v. mangafodipir following oxaliplatin. Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir. Funding.

show abstract

Section: Discussionmentioning

confidence: 99%

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Coriat¹,

Alexandre²,

Nicco³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Thus, oxaliplatin treatment causes a global change in ion channel expression that leads to a higher membrane potential and, thus, more robust firing of TRP channels. Additionally, modeling experiments have suggested that the reduction in potassium current in internodal regions of myelinated axons could lead to the nerve fiber defects first observed by Adelsberger, et al with action potential trains, and thus a stronger central response following a small peripheral stimulus[78]. The acute and chronic ion changes, however, were not considered.…”

Section: Mechanisms Of Peripheral Neuropathymentioning

confidence: 99%

Mechanisms of distal axonal degeneration in peripheral neuropathies

Cashman

Höke²

2015

Neuroscience Letters

165

181

View full text Add to dashboard Cite

Peripheral neuropathy is a common complication of a variety of diseases and treatments, including diabetes, cancer chemotherapy, and infectious causes (HIV, hepatitis C, and Campylobacter jejuni). Despite the fundamental difference between these insults, peripheral neuropathy develops as a combination of just six primary mechanisms: altered metabolism, covalent modification, altered organelle function and reactive oxygen species formation, altered intracellular and inflammatory signaling, slowed axonal transport, and altered ion channel dynamics and expression. All of these pathways converge to lead to axon dysfunction and symptoms of neuropathy. The detailed mechanisms of axon degeneration itself have begun to be elucidated with studies of animal models with altered degeneration kinetics, including the slowed Wallerian degeneration (Wlds) and Sarmknockout animal models. These studies have shown axonal degeneration to occur througha programmed pathway of injury signaling and cytoskeletal degradation. Insights into the common disease insults that converge on the axonal degeneration pathway promise to facilitate the development of therapeutics that may be effective against other mechanisms of neurodegeneration.

show abstract

“…Interestingly, both of these studies also found increased expression of hyperpolarization-activated channels (HCNs) permeable to both K + and Na + , which are known to increase nociceptor excitability and spontaneous firing in other pain conditions [27]. A simulation study has shown that oxaliplatin-induced decreases in potassium channel function and increases in sodium channel function can account for the observed nociceptor hyperexcitability [28]. In support of these findings, use of a voltage-gated K + channel opener, retigabine, to encourage neuronal hyperpolarization has been found to be effective in a mouse model of cisplatin neuropathy [29].…”

Section: Neuronal Alterations Associated With Cipnmentioning

confidence: 99%

Mechanisms Involved in the Development of Chemotherapy-Induced Neuropathy

2015

View full text Add to dashboard Cite

SUMMARY Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition seen in patients undergoing treatment with common agents such as vincristine, paclitaxel, oxaliplatin and bortezomib. The mechanisms of this condition are diverse, and include an array of molecular and cellular contributions. Current research implicates genetic predispositions to this condition, which then may influence cellular responses to chemotherapy. Processes found to be influenced during CIPN include increased expression of inflammatory mediators, primarily cytokines, which can create cascading effects in neurons and glia. Changes in ion channels and neurotransmission, as well as changes in intracellular signaling and structures have been implicated in CIPN. This review explores these issues and suggests considerations for future research.

show abstract

A possible link of oxaliplatin‐induced neuropathy with potassium channel deficit

Abstract: A combination of sodium channel blockers with drugs that obstruct the blockage of potassium channels or contribute to their opening could be effective in preventing oxaliplatin-induced "hyperexcitability."

Cited by 22 publications

References 39 publications

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Treatment of oxaliplatin-induced peripheral neuropathy by intravenous mangafodipir

Mechanisms of distal axonal degeneration in peripheral neuropathies

Mechanisms Involved in the Development of Chemotherapy-Induced Neuropathy

Contact Info

Product

Resources

About