1Principal, Trimurti Shikshan Prasark Mandals, Trimurti Institute of Pharmacy, Paldhi Bk, Near KBCNMU, Opp Govind Hotel, Tal Dharangaon, Dist Jalgaon 425103. Email: deshmukhta1975@gmail.com
2*PhD Candidate, TVES's Hon. Loksevak Madukarrao Chaudhari College of Pharmacy, Faizpur-425503, Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon. Email: mohinisarode@gmail.com
*Corresponding Author: Ms. Mohini Vilas Sarode, PhD Candidate, TVES's Hon. Loksevak Madukarrao Chaudhari College of Pharmacy, Faizpur-425503, Kavayitri Bahinabai Chaudhari North Maharashtra University, Jalgaon. Email: mohinisarode@gmail.com
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and debilitating adverse effect associated with the use of multiple chemotherapeutic agents, including paclitaxel, oxaliplatin, vincristine, and bortezomib. These agents, despite their antineoplastic efficacy, share a convergent yet distinct capability to inflict neurotoxicity through varied molecular mechanisms, targeting neuronal ion channels, mitochondrial dynamics, neuroinflammation, and axonal integrity.
Methods: This project comprehensively evaluates and compares the pharmacological and molecular mechanisms underlying the development of CIPN across these agents. Detailed behavioral assays and histopathological examinations were employed to assess the extent of neuropathy in animal models, while ELISA and Western blot analyses were conducted to quantify the expression of key inflammatory mediators (TNF-α, IL-1β, IL-6), oxidative stress markers (MDA, SOD, GPx), and neuroprotective factors (NGF, BDNF).
Mechanistic Analysis: Mechanistic analysis revealed that each chemotherapeutic agent invokes unique pathways: paclitaxel predominantly triggers toll-like receptor 4 (TLR4)-mediated neuroinflammation, oxaliplatin induces hyperexcitability via sodium channel modulation and mitochondrial dysfunction, vincristine disrupts microtubule transport leading to axonal degeneration, and bortezomib enhances endoplasmic reticulum stress and proteasome inhibition. Through bioinformatics and molecular docking studies, novel therapeutic targets such as sigma-1 receptors, Nrf2 pathway modulators, and chemokine receptor CX3CR1 were identified, suggesting potential neuroprotective interventions.
Conclusion: Collectively, the findings from this thesis provide in-depth mechanistic insights into CIPN and lay the groundwork for target-specific therapeutic strategies. The study contributes significantly to the field of neuropharmacology and advocates for personalized neuropathy management in cancer chemotherapy regimens.
Keywords: Chemotherapy-induced peripheral neuropathy, neuroinflammation, oxidative stress, molecular mechanisms, therapeutic targets, chemotherapeutic agents
How to cite this article: Deshmukh TA, Sarode MV. Molecular Mechanistic Comparison of Chemotherapeutic agents in Chemotherapy-induced Peripheral Neuropathy. Int J Drug Deliv Technol. 2026;16(12s): 864-879. DOI: 10.25258/ijddt.16.12s.102
Source of support: Nil.
Conflict of interest: None