Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) represents one of the most prevalent and potentially disabling side effects due to the use of anticancer drugs, one of the primary neuropathies detected is peripheral neuropathy induced by administration of taxanes, including paclitaxel. It has been demonstrated that gut microbiota is crucial for the therapeutic effect of chemotherapeutic drugs for inhibiting tumor growth and contributed to the pathogenesis of the CIPN. The use of nutraceuticals has receiving growing attention from the research community due to their phytochemical, biological, and pharmacological properties. It has been demonstrated that probiotic formulations may both reduce inflammation and modulate the expression of pain receptors. Our studies tested the efficacy of a probiotic formulation, SLAB51, in preventing paclitaxel-induced neuropathy. Interestingly, our probiotic formulation was able to keep the gut integrity, preserving its functionality, in CIPN-mice, moreover, it prevented the mechanical and cold hypersensitivity induced in paclitaxel-mice. Additionally, ex-vivo analysis showed that in CIPN-mice the pro-biotic treatment increased the expression of opioid and cannabinoid receptors in spinal cord, it prevented in the reduction in nerve fiber damage in the paws and modulated the serum proinflammatory cytokines concentration. On basis of these data, the use of this specific probiotic formulation may represent a valid adjuvant agent to paclitaxel, useful and not toxic for long-lasting therapies.

Highlights

  • Chemotherapeutics are commonly used for tumor therapy, but they trigger numerous detrimental side effects

  • Neurotoxicity ininduced by PTX is ascribed to altered microtubule structure, which induces enhanced microtubule stability by increasing acetylated α-tubulin triggering neuropathic pain, but it has been recently reported that PTX causes inflammation in DRG neurons in culture [48,49]

  • The mechanism by which PTX injures peripheral sensory fibers is not identified, it has been indicated that PTX impairs axoplasmic transport [50], leads to neuronal mitochondria dysfunction [51], and supports epithelial damage leading to axonal degeneration [52]

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Summary

Introduction

Chemotherapeutics are commonly used for tumor therapy, but they trigger numerous detrimental side effects. In this work, we tested the hypothesis that the probiotic formulation SLAB51 could counteract PTX-induced neuropathic pain in vivo For this purpose, we tested the probiotics in mice treated with PTX evaluating nociceptive behavior and analyzing the inflammatory and the biomolecular pathway involved in CIPN and the Biomedicines 2021, 9, x FOR PEER REVIEW. We tested the probiotics in mice treated with PTX evaluating nociceptive behavior and analyzing the inflammatory and the biomolecular pathway involved in CIPN and the Biomedicines 2021, 9, x FOR PEER REVIEW Based on this evidence, in this work, we tested the hypothesis that the probiotic for of 15 mulation SLAB51 could counteract PTX-induced neuropathic pain in vivo.

Methods
Procedures
Behavioral Pain Tests
Ex Vivo Experiments
Western Blot Analysis
Immunohistochemistry Analyses
Statistical Analyses
Probiotic Treatment Reduces Colon Tissue Damage
Behavioral tests:
ProbioticinTreatment
Western
Western blotting analyses
Probiotic Treatment Counteracts the Increase of Neuropathic Pain Proteins
Effects of the Probiotics on Inflammatory Markers in Serum
Conclusions
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