Role of inflammation and oxidative stress in chemotherapy-induced neurotoxicity.

Immunol Res

Division of Basic Medical Sciences, Indian Council of Medical Research, New Delhi, India.

Published: December 2022

Chemotherapeutic agents may adversely affect the nervous system, including the neural precursor cells as well as the white matter. Although the mechanisms are not completely understood, several hypotheses connecting inflammation and oxidative stress with neurotoxicity are now emerging. The proposed mechanisms differ depending on the class of drug. For example, toxicity due to cisplatin occurs due to activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), which alters hippocampal long-term potentiation. Free radical injury is also involved in the cisplatin-mediated neurotoxicity as dysregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) has been seen which protects against the free radical injury by regulating glutathione S-transferases and hemeoxygenase-1 (HO-1). Thus, correcting the imbalance between NF-κB and Nrf2/HO-1 pathways may alleviate cisplatin-induced neurotoxicity. With newer agents like bortezomib, peripheral neuropathy occurs due to up-regulation of TNF-α and IL-6 in the sensory neurons. Superoxide dismutase dysregulation is also involved in bortezomib-induced neuropathy. This article reviews the available literature on inflammation and oxidative stress in neurotoxicity caused by various classes of chemotherapeutic agents. It covers the conventional medicines like platinum compounds, vinca alkaloids, and methotrexate, as well as the newer therapeutic agents like immunomodulators and immune checkpoint inhibitors. A better understanding of the pathophysiology will lead to further advancement in strategies for management of chemotherapy-induced neurotoxicity.

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Source
http://dx.doi.org/10.1007/s12026-022-09307-7DOI Listing

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