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Original Research

Open Access

The effect of ozonation of bupivacaine on bupivacaine-induced neurotoxicity in rats

  • Mehmet Ali Harbelioğlu1
  • Yeliz Kılıç2,*,
  • Mehmet Sacit Güleç2

1Department of Anesthesiology and Reanimation, Çerkezköy State Hospital, 59500 Tekirdağ, Turkey

2Department of Anesthesiology and Reanimation, Faculty of Medicine, Osmangazi University, 26040 Eskişehir, Turkey

DOI: 10.22514/sv.2024.030 Vol.20,Issue 3,March 2024 pp.71-80

Submitted: 28 July 2023 Accepted: 12 September 2023

Published: 08 March 2024

*Corresponding Author(s): Yeliz Kılıç E-mail:


Bupivacaine-induced neurotoxicity (BIN) is common condition associated with free oxygen radicals based degenerative cellular changes. Morever, a apoptotic damages increase the occurences of the BIN. Ozone is a medical gas widely used in the treatment of degenerative diseases, due to its antioxidant and cytoprotective effects. The aim of the study was to investigate the effects of ozonation of bupivacaine in reducing or preventing BIN. Sixty male rats were randomly and equally divided into three groups: control (distilled water), bupivacaine and ozonated bupivacaine. The sciatic nerve was surgically dissected under anesthesia and distilled water, bupivacaine or ozonated bupivacaine was injected perineurally according to the group. The nerve samples were then extracted on 3rd and 7th days, and were examined using immunohistochemical stainings and Terminal Transferase dUTP Nick End Labeling (TUNEL) staining. The effect of ozonation of bupivacaine, on the motor and sensory functions of the sciatic nerves was examined and compated against that of the bupivacaine. H-score analyzes of neuroflament, S100, superoxide dismutase, and Tumor necrosis factor (TNF)-alpha immunostainings, and apoptotic index values after TUNEL staining were used for the assessment of the efficiency levels. The findings in this paper show that ozonation of bupivacaine statistically reduced neurotoxicity in both the 3rd and 7th day groups. No significant differences between bupivacaine and ozonated bupivacaine groups was obtained from the sensory and motor functional tests. No deterioration in the biochemical structure of bupivacaine was induced by the ozonation. The findings in this paper highlight the effectiveness of the, ozonation of bupivacaine in reducing BIN. There were also no significant differences in the resolution times of motor and sensory blocks between ozonated bupivacaine and bupivacaine alone groups.


Bupivacaine; Bupivacaine-induced neurotoxicity; Ozonation; Regional anesthesia

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Mehmet Ali Harbelioğlu,Yeliz Kılıç,Mehmet Sacit Güleç. The effect of ozonation of bupivacaine on bupivacaine-induced neurotoxicity in rats. Signa Vitae. 2024. 20(3);71-80.


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