OSCR

8-Aminoguanine protects against paclitaxel-induced neural degeneration and mechanical allodynia.

Overview

Authors: Lori A Birder1,2, Amanda Wolf-Johnston1, Jonathan Franks3, Mara LG Sullivan3, Simon C Watkins3, Anthony J Kanai1,2, Vladimir B Ritov2, Edwin K Jackson2
ORCID iDs: Simon C Watkins
  1. Renal-Electrolyte Division, Department of Medicine
  2. Department of Pharmacology and Chemical Biology, and
  3. Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Institutions: University of Pittsburgh (United States)
Journal: JCI insight, volume 11, issue 7, article e202639
Dates: received 18 November 2025; accepted 12 February 2026; published online 8 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1172/jci.insight.202639 · PMID 41948937 · PMCID PMC13134735 · OpenAlex W7151348857
Open access: gold, a free copy (OpenAlex)
Status: code on request
Categories: rat (organism), other condition (population), pain (population), cellular / molecular (subfield)
Methods: Statistics, Connectivity
Keywords: Cell biology, Neuroscience, Oncology, Breast cancer, Mitochondria, Neurodegeneration
MeSH: Guanine*, Hyperalgesia*, Nerve Degeneration*, Paclitaxel*, Peripheral Nervous System Diseases*, Animals, Disease Models, Animal, Female, Purine-Nucleoside Phosphorylase, Rats, Rats, Sprague-Dawley (* major topic)
Topic: Cancer Treatment and Pharmacology (Oncology, Medicine), according to OpenAlex
Funding: Richard King Mellon Foundation (11903); National Institutes of Health (R01 DK135076, U54 DK137329)
Citations: not cited yet (Europe PMC); 59 references in the paper

Abstract

Current treatment protocols for most types of cancers require chemotherapeutic agents that are associated with significant side effects, including chemotherapy-induced peripheral neuropathy (CIPN). Currently, there are no effective CIPN prevention strategies, and current treatment approaches remain limited. The enzyme purine nucleoside phosphorylase (PNPase) actively modulates both oxidative injury and cellular damage. Here, we tested the hypothesis that the signs and symptoms of CIPN are due to a chemotherapy-induced dysregulation of the purine metabolome. We assessed the effect of PNPase inhibition on paclitaxel-induced (PAC-induced) CIPN. Female adult Sprague-Dawley rats were treated with PAC and randomized to oral treatment with either the PNPase inhibitor 8-aminoguanine (8-AG) or its vehicle. Some rats were injected with shRNA against PNPase prior to PAC injections. PAC-treated rats exhibited multiple abnormalities: mechanical allodynia and changes in damaging purines, intraepidermal nerve fiber (IENF) density, and signaling cascades involved in mitochondrial disruption and axonal damage. Inhibition of PNPase improved behavioral function (mechanical allodynia), rescued the loss/damage of IENF, and normalized markers for mitochondrial dysfunction and nerve damage. These findings support the hypothesis that inhibition of PNPase prevented (and potentially reversed) CIPN through several mechanisms that included a reduction in neuronal damage and development of mechanical allodynia.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data availability

Data are be available in the Harvard Database Repository, which uses DataverseProject open-source research data repository software (https://doi.org/10.7910/DVN/EJAPIM), Harvard Dataverse, V1, in the paper’s supplemental material, or from the corresponding author upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 6 keywords, 11 MeSH terms, 2 funders, 57 references.

Cite

This paper

Birder, L. A., Wolf-Johnston, A., Franks, J., Sullivan, M. L., Watkins, S. C., Kanai, A. J., Ritov, V. B., & Jackson, E. K. (2026). 8-Aminoguanine protects against paclitaxel-induced neural degeneration and mechanical allodynia. JCI insight, 11(7), e202639. https://doi.org/10.1172/jci.insight.202639

BibTeX

@article{birder20268,
author = {Birder, Lori A and Wolf-Johnston, Amanda and Franks, Jonathan and Sullivan, Mara LG and Watkins, Simon C and Kanai, Anthony J and Ritov, Vladimir B and Jackson, Edwin K},
title = {{8-Aminoguanine protects against paclitaxel-induced neural degeneration and mechanical allodynia}},
journal = {JCI insight},
year = {2026},
month = apr,
volume = {11},
number = {7},
pages = {e202639},
publisher = {American Society for Clinical Investigation},
issn = {2379-3708},
doi = {10.1172/jci.insight.202639},
url = {https://doi.org/10.1172/jci.insight.202639},
pmid = {41948937},
pmcid = {PMC13134735}
}

RIS

TY - JOUR
AU - Birder, Lori A
AU - Wolf-Johnston, Amanda
AU - Franks, Jonathan
AU - Sullivan, Mara LG
AU - Watkins, Simon C
AU - Kanai, Anthony J
AU - Ritov, Vladimir B
AU - Jackson, Edwin K
TI - 8-Aminoguanine protects against paclitaxel-induced neural degeneration and mechanical allodynia
T2 - JCI insight
J2 - JCI Insight
PY - 2026
DA - 2026/04/08
VL - 11
IS - 7
SP - e202639
SN - 2379-3708
PB - American Society for Clinical Investigation
DO - 10.1172/jci.insight.202639
UR - https://doi.org/10.1172/jci.insight.202639
LA - en
ER -

CSL-JSON

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"language": "en",
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