New perspective for an old drug: Can naloxone be considered an antioxidant agent?

Rossana Migheli; Giada Lostia; Grazia Galleri; Gaia Rocchitta; Pier Andrea Serra; Ilaria Campesi; Valentina Bassareo; Elio Acquas; Alessandra T Peana

doi:10.1016/j.bbrep.2023.101441

New perspective for an old drug: Can naloxone be considered an antioxidant agent?

Biochem Biophys Rep. 2023 Feb 20:34:101441. doi: 10.1016/j.bbrep.2023.101441. eCollection 2023 Jul.

Authors

Rossana Migheli¹, Giada Lostia¹, Grazia Galleri¹, Gaia Rocchitta¹, Pier Andrea Serra¹, Ilaria Campesi², Valentina Bassareo³, Elio Acquas⁴, Alessandra T Peana¹

Affiliations

¹ Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100, Sassari, Italy.
² Department of Biomedical Sciences, University of Sassari, 07100, Sassari, Italy.
³ Department of Biomedical Sciences and Center of Excellence for the Study of Neurobiology of Addiction, University of Cagliari, 09042, Monserrato, Cagliari, Italy.
⁴ Department of Life and Environmental Sciences and Center of Excellence for the Study of Neurobiology of Addiction, University of Cagliari, 09042, Monserrato, Cagliari, Italy.

Abstract

Background: Experimental evidence indicates that Naloxone (NLX) holds antioxidant properties. The present study aims at verifying the hypothesis that NLX could prevent oxidative stress induced by hydrogen peroxide (H₂O₂) in PC12 cells.

Methods: To investigate the antioxidant effect of NLX, initially, we performed electrochemical experiments by means of platinum-based sensors in a cell-free system. Subsequently, NLX was tested in PC12 cells on H₂O₂-induced overproduction of intracellular levels of reactive-oxygen-species (ROS), apoptosis, modification of cells' cycle distribution and damage of cells' plasma membrane.

Results: This study reveals that NLX counteracts intracellular ROS production, reduces H₂O₂-induced apoptosis levels, and prevents the oxidative damage-dependent increases of the percentage of cells in G2/M phase. Likewise, NLX protects PC12 cells from H₂O₂- induced oxidative damage, by preventing the lactate dehydrogenase (LDH) release. Moreover, electrochemical experiments confirmed the antioxidant properties of NLX.

Conclusion: Overall, these findings provide a starting point for studying further the protective effects of NLX on oxidative stress.

Keywords: Hydrogen peroxide; Naloxone; Oxidative stress; PC12cells; Platinum-based sensors.