Article Data

  • Views 564
  • Dowloads 116

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: yelizk@ogu.edu.tr

Abstract

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.


Keywords

Bupivacaine; Bupivacaine-induced neurotoxicity; Ozonation; Regional anesthesia


Cite and Share

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.

References

[1] Zhang Y, Feng S, Cheng X, Lou K, Liu X, Zhuo M, et al. The potential value of exosomes as adjuvants for novel biologic local anesthetics. Frontiers in Pharmacology. 2023; 14: 1112743.

[2] Xiang Y, Wang W, Jing S, Zhang Z, Wang D. Vocal fold paralysis and cauda equina syndrome following spinal-epidural anesthesia: a case report. Medicine. 2021; 100: e24374.

[3] Cherobin ACFP, Tavares GT. Safety of local anesthetics. Anais Brasileiros De Dermatologia 2020; 95: 82–90.

[4] Sun L, Yuan R. LncRNA SNHG12 ameliorates bupivacaine-induced neurotoxicity by sponging miR-497–5p to upregulate NLRX1. Human & Experimental Toxicology. 2022; 41: 096032712210890.

[5] Chen L, Zhuang K. Kaempferol counteracts bupivacaine-induced neurotoxicity in mouse dorsal root ganglia neurons by regulating TRAF6-dependent NF-κB signaling. The Kaohsiung Journal of Medical Sciences. 2023; 39: 710–717.

[6] Li L, Ye X, Lu A, Zhou S, Liu H, Liu Z, et al. Hyperglycemia magnifies bupivacaine‐induced cell apoptosis triggered by mitochondria dysfunction and endoplasmic reticulum stress. Journal of Neuroscience Research. 2013; 91: 786–798.

[7] Zhao W, Liu Z, Yu X, Lai L, Li H, Liu Z, et al. ITRAQ proteomics analysis reveals that PI3K is highly associated with bupivacaine-induced neurotoxicity pathways. Proteomics. 2016; 16: 564–575.

[8] Zhang L, Zhang L, Guo F. MiRNA-494-3p regulates bupivacaine-induced neurotoxicity by the CDK6-PI3K/AKT signaling. Neurotoxicity Research. 2021; 39: 2007–2017.

[9] Bedard K, Krause K. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiological Reviews. 2007; 87: 245–313.

[10] Li Y, Zhao W, Yu X, Li F, Liu Z, Li L, et al. Activation of p47phox as a mechanism of bupivacaine-induced burst production of reactive oxygen species and neural toxicity. Oxidative Medicine and Cellular Longevity. 2017; 2017: 8539026.

[11] Liu M, Wu X, Cui Y, Liu P, Xiao B, Zhang X, et al. Mitophagy and apoptosis mediated by ROS participate in AlCl3-induced MC3T3-E1 cell dysfunction. Food and Chemical Toxicology. 2021; 155: 112388.

[12] Khan SA, Re K, Gandhi J, Liang R, Patel S, Joshi G, et al. Clinical utility of ozone therapy and hyperbaric oxygen therapy in degenerative disc disease. Medical Gas Research. 2023; 13: 1–6.

[13] Serra MEG, Baeza-Noci J, Mendes Abdala CV, Luvisotto MM, Bertol CD, Anzolin AP. The role of ozone treatment as integrative medicine. An evidence and gap map. Frontiers in Public Health. 2023; 10: 1112296.

[14] Schwartz A, Sánchez GM, Sabah F, Avilés MH. Madrid declaration on ozone therapy. 3rd edn. International Scientific Committee of Ozone Therapy (ISCO3): Madrid. 2020.

[15] Yanchu L, Rong P, Rong C, Li Z, Xiaoyan Y, Feng W. Ozone therapy for high-grade glioma: an overview. Frontiers in Oncology. 2023; 13: 1161206.

[16] Ali Erdogan M, Polat A, Yucel A, Aydogan MS, Parlakpinar H, Tekin S, et al. Effects of perineural administration of dexmedetomidine in combination with levobupivacaine in a rat sciatic nerve block. Current Therapeutic Research. 2013; 74: 74–78.

[17] Brummett C, Norat M, Palmisano J, Lydic R. Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat. Anesthesiology. 2008; 109: 502–511.

[18] Langford DJ, Mogil JS. Pain testing in the laboratory mouse. Anesthesia and Analgesia in Laboratory Animals. 2008; 83: 549–560.

[19] Gürpınar T, Ekerbiçer N, Uysal N, Barut T, Tarakçı F, Tuglu MI. The effects of the melatonin treatment on the oxidative stress and apoptosis in diabetic eye and brain. The Scientific World Journal. 2012; 2012: 498489.

[20] Öztürk Ş, Sönmez PK, Özdemir I, Topdağı YE, Tuğlu MI. Antiapoptotic and proliferative effect of bone marrow-derived mesenchymal stem cells on experimental Asherman model. Cukurova Medical Journal. 2019; 44: 434–446

[21] Numata M, Morinaga S, Watanabe T, Tamagawa H, Yamamoto N, Shiozawa M, et al. The clinical significance of SWI/SNF complex in pancreatic cancer. International Journal of Oncology. 2013; 42: 403–410.

[22] W. Cohen Jacob. Statistical power analysis for the behavioral sciences. 2nd edn. Lawrence Erlbaum Associates: Hillsdale, New Jersey. 1988.

[23] Verlinde M, Hollmann MW, Stevens MF, Hermanns H, Werdehausen R, Lirk P. Local anesthetic-induced neurotoxicity. International Journal of Molecular Sciences. 2016; 17: 339.

[24] Nouette-Gaulain K, Capdevila X, Rossignol R. Local anesthetic ‘in-situ’ toxicity during peripheral nerve blocks. Current Opinion in Anaesthesiology. 2012; 25: 589–595.

[25] Koo CH, Baik J, Shin HJ, Kim JH, Ryu JH, Han SH. Neurotoxic effects of local anesthetics on developing motor neurons in a rat model. Journal of Clinical Medicine. 2021; 10: 901.

[26] An K, Elkassabany NM, Liu J. Dexamethasone as adjuvant to bupivacaine prolongs the duration of thermal antinociception and prevents bupivacaine-induced rebound hyperalgesia via regional mechanism in a mouse sciatic nerve block model. PLOS ONE. 2015; 10: e0123459.

[27] Mueller M, Wacker K, Ringelstein EB, Hickey WF, Imai Y, Kiefer R. Rapid response of identified resident endoneurial macrophages to nerve injury. The American Journal of Pathology. 2001; 159: 2187–2197.

[28] E Q, Wu Y, Liang X, Chen M, Peng J, Zhou Z, et al. Establishment of an animal model of sciatic nerve injury induced by local anesthetics. Human & Experimental Toxicology. 2023; 42: 096032712311733.

[29] Wang T, Zheng L, Zhang W. Hesperidin alleviates bupivacaine anesthesia‐induced neurotoxicity in SH‐SY5Y cells by regulating apoptosis and oxidative damage. Journal of Biochemical and Molecular Toxicology. 2021; 35: e22787.

[30] Xue X, Lv Y, Leng Y, Zhang Y. Autophagy activation attenuates the neurotoxicity of local anaesthetics by decreasing caspase-3 activity in rats. Brazilian Journal of Anesthesiology. 2020; 70: 627–634. (In Portuguese)

[31] Zhao T, Wang Q. Capillarisin protects SH-SY5Y cells against bupivacaine-induced apoptosis via ROS-mediated PI3K/PKB pathway. Life Sciences. 2020; 259: 118279.

[32] Hidalgo-Tallón FJ, Torres-Morera LM, Baeza-Noci J, Carrillo-Izquierdo MD, Pinto-Bonilla R. Updated review on ozone therapy in pain medicine. Frontiers in Physiology. 2022; 13: 840623.

[33] Masan J, Sramka M, Rabarova D. The possibilities of using the effects of ozone therapy in neurology. Neuroendocrinology Letters. 2021; 42: 13–21.

[34] Ogut E, Yildirim Fb, Sarikcioglu L, Aydin Ma, Demir N. Neuroprotective effects of ozone therapy after sciatic nerve cut injury. The Kurume Medical Journal. 2018; 65: 137–144.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Chemical Abstracts Service Source Index The CAS Source Index (CASSI) Search Tool is an online resource that can quickly identify or confirm journal titles and abbreviations for publications indexed by CAS since 1907, including serial and non-serial scientific and technical publications.

Index Copernicus The Index Copernicus International (ICI) Journals database’s is an international indexation database of scientific journals. It covered international scientific journals which divided into general information, contents of individual issues, detailed bibliography (references) sections for every publication, as well as full texts of publications in the form of attached files (optional). For now, there are more than 58,000 scientific journals registered at ICI.

Geneva Foundation for Medical Education and Research The Geneva Foundation for Medical Education and Research (GFMER) is a non-profit organization established in 2002 and it works in close collaboration with the World Health Organization (WHO). The overall objectives of the Foundation are to promote and develop health education and research programs.

Scopus: CiteScore 1.0 (2022) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Embase Embase (often styled EMBASE for Excerpta Medica dataBASE), produced by Elsevier, is a biomedical and pharmacological database of published literature designed to support information managers and pharmacovigilance in complying with the regulatory requirements of a licensed drug.

Submission Turnaround Time

Conferences

Top