Emerging Therapeutic Targets in Oxaliplatin-Induced Acute Peripheral Neuropathy: Biochemical Protection by Organoselenium via Redox and Ionic Regulation.
- 1Preclinical and Translational Research Group on Pain and Chronic Diseases - GPCCD, CCQFA - Federal University of Pelotas, UFPel, P.O. Box 354, Pelotas, Rio Grande do Sul96010-900, Brazil.
- 2Laboratory of Clean Organic Synthesis - LASOL, CCQFA - Federal University of Pelotas (UFPel), P.O. Box 354, Pelotas, Rio Grande do Sul96010-900, Brazil.
Abstract
Oxaliplatin (OXA), a platinum-based chemotherapeutic agent, frequently induces acute peripheral neuropathy characterized by mechanical and cold allodynia, for which effective therapeutic options remain limited. Here, we investigated the acute antinociceptive and biochemical effects of 4-amino-3-(phenylselanyl)benzenesulfonamide (4-APSB), a compound with antioxidant and antinociceptive properties, in female Wistar rats with OXA-induced acute neuropathy. Animals received OXA (4 mg/kg, i.p.) on two consecutive days and were subsequently treated with 4-APSB (1 mg/kg, i.g.) or duloxetine (30 mg/kg, i.g.) as a reference drug. Nociceptive behaviors were assessed using mechanical and cold sensitivity assays, followed by biochemical analyses in nervous tissues. OXA administration induced mechanical and cold hypersensitivity, elevated oxidative stress markers, and disrupted membrane enzyme function, reducing Na+/K+-ATPase activity and increasing acetylcholinesterase (AChE) activity. Treatment with 4-APSB significantly attenuated hypersensitivity, increased Na+/K+-ATPase and catalase activities, reduced reactive species generation, and attenuated the OXA-induced increase in AChE activity in the cerebral cortex, without affecting locomotor behavior. Collectively, these findings show that 4-APSB produces acute antinociceptive effects accompanied by the modulation of redox homeostasis, Na+/K+-ATPase activity, and AChE activity following OXA exposure. The coordinated improvement in behavioral and biochemical parameters supports the potential relevance of redox balance and membrane-associated enzyme function to the pharmacological effects of 4-APSB. These results identify 4-APSB as a promising compound for further investigation as a therapeutic strategy for OXA-induced peripheral neuropathy.
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BibTeX
@article{rocha2026emerging,
title = {{Emerging Therapeutic Targets in Oxaliplatin-Induced Acute Peripheral Neuropathy: Biochemical Protection by Organoselenium via Redox and Ionic Regulation.}},
author = {Vanessa M E da Rocha and Ketlyn P da Motta and Ana Paula B Wille and Ariana S Lima and Diéssica Padilha Dalenogare and Vinicius Costa Prado and Diego Alves and Angélica S Reis and Ethel A Wilhelm},
journal = {Chemical research in toxicology},
year = {2026},
month = sep,
doi = {10.1021/acs.chemrestox.6c00302},
url = {https://europepmc.org/article/MED/42915729},
note = {CC BY},
}
RIS
TY - JOUR
TI - Emerging Therapeutic Targets in Oxaliplatin-Induced Acute Peripheral Neuropathy: Biochemical Protection by Organoselenium via Redox and Ionic Regulation.
AU - Vanessa M E da Rocha
AU - Ketlyn P da Motta
AU - Ana Paula B Wille
AU - Ariana S Lima
AU - Diéssica Padilha Dalenogare
AU - Vinicius Costa Prado
AU - Diego Alves
AU - Angélica S Reis
AU - Ethel A Wilhelm
PY - 2026
DA - 2026/09/01
JO - Chemical research in toxicology
DO - 10.1021/acs.chemrestox.6c00302
UR - https://europepmc.org/article/MED/42915729
AB - Oxaliplatin (OXA), a platinum-based chemotherapeutic agent, frequently induces acute peripheral neuropathy characterized by mechanical and cold allodynia, for which effective therapeutic options remain limited. Here, we investigated the acute antinociceptive and biochemical effects of 4-amino-3-(phenylselanyl)benzenesulfonamide (4-APSB), a compound with antioxidant and antinociceptive properties, in female Wistar rats with OXA-induced acute neuropathy. Animals received OXA (4 mg/kg, i.p.) on two consecutive days and were subsequently treated with 4-APSB (1 mg/kg, i.g.) or duloxetine (30 mg/kg, i.g.) as a reference drug. Nociceptive behaviors were assessed using mechanical and cold sensitivity assays, followed by biochemical analyses in nervous tissues. OXA administration induced mechanical and cold hypersensitivity, elevated oxidative stress markers, and disrupted membrane enzyme function, reducing Na+/K+-ATPase activity and increasing acetylcholinesterase (AChE) activity. Treatment with 4-APSB significantly attenuated hypersensitivity, increased Na+/K+-ATPase and catalase activities, reduced reactive species generation, and attenuated the OXA-induced increase in AChE activity in the cerebral cortex, without affecting locomotor behavior. Collectively, these findings show that 4-APSB produces acute antinociceptive effects accompanied by the modulation of redox homeostasis, Na+/K+-ATPase activity, and AChE activity following OXA exposure. The coordinated improvement in behavioral and biochemical parameters supports the potential relevance of redox balance and membrane-associated enzyme function to the pharmacological effects of 4-APSB. These results identify 4-APSB as a promising compound for further investigation as a therapeutic strategy for OXA-induced peripheral neuropathy.
SN - 0893-228X
SN - 1520-5010
ER -