Etoposide- and BMY-40481-Induced Sensory Neuropathy in Mice

Abstract

The effects of high toxic doses of the anticancer drugs, etoposide and its phosphate derivative, BMY- Ultrastructurally, ganglion cell bodies had focally extensive dilation of the rough endoplasmic reticulum, mitochondrial swelling, increased numbers of phagolysosomes and prominent aggregations of microfilaments (globular filamentous bodies). Ultrastructural axonal changes occurred primarily in large, myelinated fibers and consisted of axonal swelling or loss, thinning of myelin sheaths, and a decrease in the number of organelles. This is the first report of etoposide-related sensory neuropathy in laboratory animals, a model that may be useful for the study of etoposide-related peripheral neuropathy in humans.

Short‐term recovery of chemotherapy‐induced peripheral neuropathy after treatment for pediatric non‐CNS cancer

“…Among the children treated with the Vinc/ Etop combination, the increase in total ped‐mTNSs was primarily due to an increase in sensory involvement. Etop is a topoisomerase inhibitor that has some evidence to indicate that it may contribute to degeneration of dorsal root ganglion cells, with resultant sensory neuropathy, which is consistent with our findings …”

“…Several of these agents are used commonly to treat childhood cancer, including vinca alkaloids and platinum compounds . Etoposide (Etop), a topoisomerase inhibitor, used to treat some childhood cancers, has also demonstrated the potential for neurotoxicity . Confounding the understanding of the effects of these agents on the peripheral nervous system (PNS) in children with cancer is the fact that many chemotherapy regimens used to treat childhood cancer include multiple agents that have potential for peripheral or central neurotoxicity.…”

Multiplexing Spheroid Volume, Resazurin and Acid Phosphatase Viability Assays for High-Throughput Screening of Tumour Spheroids and Stem Cell Neurospheres

“…Although etoposide is not generally regarded as a neurotoxic drug [58] there are reports which have demonstrated neurotoxicity in mice after blood-brain barrier disruption [59]–[61]. The heightened sensitivity of a sub-population of the neurosphere cells to etoposide can be explained by the presence of EGF and FGF in the culture media which limit differentiation and stimulate division.…”

“…It offers the opportunity to compare the effect of drug upon the tumour and brain thereby comparing efficacy against toxicity, enhancing the bio-relevance to human tumours in clinical practice [10], [59], [67], [68]. The correlation with previously reported experimental and clinical studies [57], [60]–[63] and the practical convenience of this assay procedure suggest that it should be considered as a possible replacement for some animal testing experiments dealing with drug efficacy, particularly in brain tumour types relevant to childhood.…”

Neurological complications of chemotherapy to the peripheral nervous system

“…This drug can cause sensory neuropathy in mice with dose-related changes in dorsal root ganglion cells, axonal degeneration of their distal and proximal processes in peripheral nerves, dorsal spinal roots, and dorsal spinal funiculi (Bregman et al, 1994). This drug can cause sensory neuropathy in mice with dose-related changes in dorsal root ganglion cells, axonal degeneration of their distal and proximal processes in peripheral nerves, dorsal spinal roots, and dorsal spinal funiculi (Bregman et al, 1994).…”