scholarly journals Therapeutic Agents for Oxaliplatin-Induced Peripheral Neuropathy; Experimental and Clinical Evidence

2021 ◽  
Vol 22 (3) ◽  
pp. 1393
Author(s):  
Takehiro Kawashiri ◽  
Keisuke Mine ◽  
Daisuke Kobayashi ◽  
Mizuki Inoue ◽  
Soichiro Ushio ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Neuropathy ◽  
Transient Receptor Potential ◽  
Clinical Evidence ◽  
Receptor Potential ◽  
Basic Research ◽  
Limiting Factor ◽  
Therapeutic Effects ◽  
Neuroprotective Effects ◽  
Transient Receptor

Oxaliplatin is an essential drug in the chemotherapy of colorectal, gastric, and pancreatic cancers, but it frequently causes peripheral neuropathy as a dose-limiting factor. So far, animal models of oxaliplatin-induced peripheral neuropathy have been established. The mechanisms of development of neuropathy induced by oxaliplatin have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory effects on neuropathy. In this review, we summarize the basic and clinical evidence for the therapeutic effects of oxaliplatin. In basic research, there are many reports of neuropathy inhibitors that target oxidative stress, inflammatory response, sodium channel, transient receptor potential (TRP) channel, glutamate nervous system, and monoamine nervous system. Alternatively, very few drugs have clearly demonstrated the efficacy for oxaliplatin-induced peripheral neuropathy in clinical trials. It is important to activate translational research in order to translate basic research into clinical research.

scholarly journals Preclinical and Clinical Evidence of Therapeutic Agents for Paclitaxel-Induced Peripheral Neuropathy

2021 ◽  
Vol 22 (16) ◽  
pp. 8733
Author(s):  
Takehiro Kawashiri ◽  
Mizuki Inoue ◽  
Kohei Mori ◽  
Daisuke Kobayashi ◽  
Keisuke Mine ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Clinical Research ◽  
Cannabinoid Receptors ◽  
Transient Receptor Potential ◽  
Clinical Evidence ◽  
Trp Channels ◽  
Receptor Potential ◽  
Limiting Factor ◽  
Neuroprotective Effects ◽  
Transient Receptor

Paclitaxel is an essential drug in the chemotherapy of ovarian, non-small cell lung, breast, gastric, endometrial, and pancreatic cancers. However, it frequently causes peripheral neuropathy as a dose-limiting factor. Animal models of paclitaxel-induced peripheral neuropathy (PIPN) have been established. The mechanisms of PIPN development have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory PIPN effects. This review summarizes the basic and clinical evidence for therapeutic or prophylactic effects for PIPN. In pre-clinical research, many reports exist of neuropathy inhibitors that target oxidative stress, inflammatory response, ion channels, transient receptor potential (TRP) channels, cannabinoid receptors, and the monoamine nervous system. Alternatively, very few drugs have demonstrated PIPN efficacy in clinical trials. Thus, enhancing translational research to translate pre-clinical research into clinical research is important.

scholarly journals Carvacrol Attenuates Hippocampal Neuronal Death after Global Cerebral Ischemia via Inhibition of Transient Receptor Potential Melastatin 7

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 231 ◽  
Author(s):  
Dae Hong ◽  
Bo Choi ◽  
A Kho ◽  
Song Lee ◽  
Jeong Jeong ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuronal Death ◽  
Transient Receptor Potential ◽  
Therapeutic Potential ◽  
Receptor Potential ◽  
Global Cerebral Ischemia ◽  
Neuroprotective Effects ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Zinc Translocation

Over the last two decades, evidence supporting the concept of zinc-induced neuronal death has been introduced, and several intervention strategies have been investigated. Vesicular zinc is released into the synaptic cleft, where it then translocates to the cytoplasm, which leads to the production of reactive oxygen species and neurodegeneration. Carvacrol inhibits transient receptor potential melastatin 7 (TRPM7), which regulates the homeostasis of extracellular metal ions, such as calcium and zinc. In the present study, we test whether carvacrol displays any neuroprotective effects after global cerebral ischemia (GCI), via a blockade of zinc influx. To test our hypothesis, we used eight-week-old male Sprague–Dawley rats, and a GCI model was induced by bilateral common carotid artery occlusion (CCAO), accompanied by blood withdrawal from the femoral artery. Ischemic duration was defined as a seven-minute electroencephalographic (EEG) isoelectric period. Carvacrol (50 mg/kg) was injected into the intraperitoneal space once per day for three days after the onset of GCI. The present study found that administration of carvacrol significantly decreased the number of degenerating neurons, microglial activation, oxidative damage, and zinc translocation after GCI, via downregulation of TRPM7 channels. These findings suggest that carvacrol, a TRPM7 inhibitor, may have therapeutic potential after GCI by reducing intracellular zinc translocation.

scholarly journals Neuro-genetic plasticity ofCaenorhabditis elegansbehavioral thermal tolerance

2019 ◽  
Author(s):  
Gregory W. Stegeman ◽  
Denise Medina ◽  
Asher D. Cutter ◽  
William S. Ryu
Keyword(s):  
Nervous System ◽  
Temperature Variation ◽  
Thermal Tolerance ◽  
Transient Receptor Potential ◽  
Behavioral Control ◽  
Receptor Potential ◽  
Adaptive Plasticity ◽  
C Elegans ◽  
Physiological Limits ◽  
Transient Receptor

AbstractBackgroundAnimal responses to thermal stimuli involve intricate contributions of genetics, neurobiology and physiology, with temperature variation providing a pervasive environmental factor for natural selection. Thermal behavior thus exemplifies a dynamic trait that requires non-trivial phenotypic summaries to appropriately capture the trait in response to a changing environment. To characterize the deterministic and plastic components of thermal responses, we developed a novel micro-droplet assay of nematode behavior that permits information-dense summaries of dynamic behavioral phenotypes as reaction norms in response to increasing temperature (thermal tolerance curves, TTC).ResultsWe found thatC. elegansTTCs shift predictably with rearing conditions and developmental stage, with significant differences between distinct wildtype genetic backgrounds. Moreover, after screening TTCs for 58C. elegansgenetic mutant strains, we determined that genes affecting thermosensation, includingcmk-1andtax-4, potentially play important roles in the behavioral control of locomotion at high temperature, implicating neural decision-making in TTC shape rather than just generalized physiological limits. However, expression of the transient receptor potential ion channel TRPA-1 in the nervous system is not sufficient to rescue rearing-dependent plasticity in TTCs conferred by normal expression of this gene, indicating instead a role for intestinal signaling involving TRPA-1 in the adaptive plasticity of thermal performance.ConclusionsThese results implicate nervous system and non-nervous system contributions to behavior, in addition to basic cellular physiology, as key mediators of evolutionary responses to selection from temperature variation in nature.

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