Pregabalin and lacosamide ameliorate paclitaxel-induced peripheral neuropathy via inhibition of JAK/STAT signaling pathway and Notch-1 receptor

Al-Massri, Khaled F.; Ahmed, Lamiaa A.; El‐Abhar, Hanan S.

doi:10.1016/j.neuint.2018.08.007

Cited by 43 publications

(36 citation statements)

References 60 publications

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“…Consistent with previous studies, [31][32][33] our results showed that repeated administrations of PTX did not cause mortality or disability in any experimental rats. In addition, PTX treatment did not show any obvious effect on either body weight or growth rate of body weight in experimental rats.…”

Section: Discussionsupporting

confidence: 93%

<p>Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway</p>

Zhao¹,

Yao²,

Li³

et al. 2020

JPR

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Background and Purpose: Neuropathic pain is a major side-effect of paclitaxel (PTX) chemotherapy. Although the precise mechanisms responsible for this pain are unclear, the activation of neuroglia and upregulation of the TLR4/NF-κB pathway are known to be involved. In this study, we determined whether electroacupuncture (EA) could limit mechanical hypersensitivity resulting from the chemotherapeutic drug PTX in rats, and investigated the potential mechanisms involved. Methods: Rats intraperitoneally received a cumulative dose of 8 mg/kg PTX (2 mg/kg per day) or vehicle control on alternate days (day 0, 2, 4 and 6). EA treatment (10 Hz, 1 mA) was applied at bilateral ST36 acupoints in rats once every other day on days 0-14. For sham EA, needles were inserted at ST36 acupoints without electrical stimulation. Mechanical allodynia was measured by mechanical withdrawal latency (MWL) of paws to a mechanical stimulus every 2 days. Protein expression of TLR4 and NF-κB p65, as well as TMEM119 and GFAP (indicators of microglia and astrocytes, respectively) in spinal cord was quantified by Western blot analysis. Levels of inflammatory cytokines IL-1β and TNF-α in spinal cord and serum were detected by ELISA. Results: Mechanical allodynia induced by PTX in both paws (right and left) of rats was significantly attenuated by EA but not sham EA treatment. In addition, EA, but not sham EA, inhibited the activation of both microglia (TMEM119) and astrocytes (GFAP) in lumbar spinal cord. Moreover, Western blot analysis revealed that protein expression of TLR4 and NF-κB in spinal cord was suppressed by EA but not sham EA treatment. PTX significantly increased inflammatory cytokines in spinal cord and serum, which were ameliorated by EA treatment but not by sham EA. Conclusion: These results indicate that EA treatment attenuates PTX-induced mechanical allodynia. The putative mechanism corroborating this finding could be related to the suppression of activated microglia and astrocytes in spinal cord, as well as the inhibition of the activated TLR4/NF-κB signaling pathway by EA treatment.

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Section: Discussionsupporting

confidence: 93%

<p>Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway</p>

Zhao¹,

Yao²,

Li³

et al. 2020

JPR

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“…Chemotherapy can form adducts with mitochondrial DNA producing inhibition of replication, disruption of transcription, and morphological abnormalities within mitochondria in DRG neurons, leading to a gradual energetic failure (Canta, Pozzi, & Carozzi, ). The increased inflammatory cascades extend to the activation of caspase‐3 to induce apoptosis, a fact that was proven in our previous report, where PTX increased the content of active caspase‐3 and p ‐p38‐MAPK in the sciatic nerve and induced neuronal apoptosis (Al‐Massri et al, ), a result that concurs with previous studies (Flatters & Bennett, ; Melli et al, ), partly through stimulating p38‐MAPK (Huang et al, ). On the other hand, BM‐MSCs administration reduced these apoptotic parameters in PTX‐induced peripheral neuropathy (Al‐Massri et al, ).…”

Section: Mscs Therapy In Cipn and Peripheral Neuropathysupporting

confidence: 90%

“…These secreted inflammatory mediators can up‐regulate the expression levels of ion channels like Na + and Ca 2+ or directly activate nociceptors implicated in mechanical and thermal hyperalgesia, causing peripheral sensitization (Mangiacavalli et al, ; Schäfers & Sorkin, ). In line with these data, our previous study demonstrated that PTX increased inflammatory mediators such as nuclear factor kappa‐B p65 (NF‐κB p65), TNF‐α, and IL‐6 in the sciatic nerve of rats (Al‐Massri et al, ). During neuropathic states, glial cells in the spinal cord are activated, along with the release of neuroactive molecules and proinflammatory cytokines, such as IL‐1β and TNF‐α, which have been directly implicated in the excitability pattern change of spinal and sensory neurons (Pabreja, Dua, Sharma, Padi, & Kulkarni, ; Wang, Couture, & Hong, ).…”

Section: Mscs Therapy In Cipn and Peripheral Neuropathysupporting

confidence: 64%

“…Another pathway involved in neuropathic pain is the p38‐MAPK signal, which activates the transcriptional factor NF‐κB and its related proinflammatory cytokines, as TNF‐α and IL‐6 (Kumar, Boehm, & Lee, ). Hence, the phosphorylation/activation of p38‐MAPK in the PTX‐induced peripheral neuropathy could be responsible for the activation of inflammatory pathway as described in our previous research (Al‐Massri et al, ). Furthermore, blocking CX3CL1 was found to decrease p38‐MAPK activity and thus blocking the neuronal apoptosis and development of mechanical allodynia induced by PTX (Huang et al, ).…”

Section: Mscs Therapy In Cipn and Peripheral Neuropathysupporting

confidence: 53%

“…Oxidative stress is identified to be responsible for the neuronal damage in different models of neuropathies such as diabetic neuropathy, acrylamide‐induced neuropathy, and CIPN (Al‐Massri, Ahmed, & El‐Abhar, ; Negi, Kumar, Joshi, & Sharma, ; Prasad & Muralidhara, ). Oxidative stress–mediated neurodegeneration can execute through bioenergetic failure, depletion of antioxidant defenses, biomolecular damage, microtubular disruption, ion channel activation, demyelination, neuroinflammation, mitophagy impairment, and neuronal death through apoptosis (Salvemini et al, ; Ta et al, ).…”

Section: Mscs Therapy In Cipn and Peripheral Neuropathymentioning

confidence: 99%

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Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

Al-Massri

Ahmed

El‐Abhar

2019

J Tissue Eng Regen Med

Self Cite

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Chemotherapeutic drugs may disrupt the nervous system and cause chemotherapyinduced peripheral neuropathy (CIPN) as side effects. There are no completely successful medications for the prevention or treatment of CIPN. Many drugs such as tricyclic antidepressants and anticonvulsants have been used for symptomatic treatment of CIPN. Unfortunately, these drugs often give only partial relief or have dose-limiting side effects. Thus, the treatment of CIPN becomes a challenge because of failure to regenerate and repair the injured neurons. Mesenchymal stem cell (MSC) therapy is a new attractive approach for CIPN. Evidence has demonstrated that MSCs play important roles in reducing oxidative stress, neuroinflammation, and apoptosis, as well as mediating axon regeneration after nerve damage in several experimental studies and some clinical trials. We will briefly review the pathogenesis of CIPN, traditional therapies used and their drawbacks as well as therapeutic effects of MSCs, their related mechanisms, future challenges for their clinical application, and the additional benefit of their combination with pharmacological agents. MSCs-based therapies may provide a new therapeutic strategy for patients suffering from CIPN where further investigations are required for studying their exact mechanisms. Combined therapy with pharmacological agents can provide another promising option for enhancing MSC therapy success while limiting its adverse effects.

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Apatinib weakens resistance of gastric cancer cells to paclitaxel by suppressing JAK/STAT3 signaling pathway

Bei

Xue

et al. 2021

Drug Development Research

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Apatinib has experienced a long‐term study in enhancing the sensitivity of various cancer cells to chemotherapy drugs. Currently, researches show that apatinib could attenuate the resistance of gastric cancer (GC) cells to paclitaxel (PTX), but the mechanism has not been fully elucidated, which therefore was explored in this study. PTX‐resistant GC cell, namely HGC‐27R, was established by exposure to stepwise‐increasing PTX. The cell viability of HGC‐27 and HGC‐27R under PTX or apatinib at different concentrations was assessed by CCK‐8 assay, while scratching test and invasion assay were used for investigating the harmful influence of GC cells resistance to PTX. The function of apatinib in HGC‐27R was studied by performing functional experiments (flow cytometry, scratching test, and invasion assay). Western blot was performed to measure the expressions of proteins concerning apoptosis, epithelial‐mesenchymal transition and janus‐activated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. PTX‐resistant GC cell, namely HGC‐27R, was successively constructed. HGC‐27R cells showed resistance to PTX by promoting migratory and invasive capabilities. Apatinib not only inhibited cell viability of HGC‐27 and HGC‐27R, but also combined with PTX to suppress that of HGC‐27R. Apatinib enhanced apoptosis, diminished migration and invasion of HGC‐27R cells, elevated proapoptotic protein expression, and reduced Bcl‐2, vimentin, snail, MMP‐3, MMP‐2, and MMP‐9 expressions. The phosphorylation of JAK2 and STAT3 was repressed by apatinib. JAK2 partially reversed the effect of apatinib on enhancing sensitivity of GC cells to PTX. Apatinib strengthened sensitivity of GC cells to PTX by inhibiting JAK/STAT3 signaling pathway.

show abstract

Pregabalin and lacosamide ameliorate paclitaxel-induced peripheral neuropathy via inhibition of JAK/STAT signaling pathway and Notch-1 receptor

Cited by 43 publications

References 60 publications

<p>Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway</p>

<p>Electroacupuncture Treatment Attenuates Paclitaxel-Induced Neuropathic Pain in Rats via Inhibiting Spinal Glia and the TLR4/NF-κB Pathway</p>

Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

Apatinib weakens resistance of gastric cancer cells to paclitaxel by suppressing JAK/STAT3 signaling pathway

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