Antioxidant activity of lidocaine, bupivacaine, and ropivacaine in aqueous and lipophilic environments : an experimental and computational study

Kavčič, Hana (author), Jug, Urška (author), Mavri, Janez (author), Umek, Nejc (author)

Introduction: Local anesthetics are widely recognized pharmaceutical compounds with various clinical effects. Recent research indicates that they positively impact the antioxidant system and they may function as free radical scavengers. We hypothesize that their scavenging activity is influenced by the lipophilicity of the environment. Methods: We assessed the free radical scavenging capacity of three local anesthetics (lidocaine, bupivacaine, and ropivacaine) using ABTS, DPPH, and FRAP antioxidant assays. We also employed quantum chemistry methods to find the most probable reaction mechanism. The experiments were conducted in an aqueous environment simulating extracellular fluid or cytosol, and in a lipophilic environment (n-octanol) simulating cellular membranes or myelin sheets. Results: All local anesthetics demonstrated ABTS˙+ radical scavenging activity, with lidocaine being the most effective. Compared to Vitamin C, lidocaine exhibited a 200-fold higher half-maximal inhibitory concentration. The most thermodynamically favorable and only possible reaction mechanism involved hydrogen atom transfer between the free radical and the -C-H vicinal to the carbonyl group. We found that the antioxidant activity of all tested local anesthetics was negligible in lipophilic environments, which was further confirmed by quantum chemical calculations. Conclusion: Local anesthetics exhibit modest free radical scavenging activity in aqueous environments, with lidocaine demonstrating the highest activity. However, their antioxidant activity in lipophilic environments, such as cellular membranes, myelin sheets, and adipose tissue, appears to be negligible. Our results thus show that free radical scavenging activity is influenced by the lipophilicity of the environment.

• Language: English
• Keywords: antioksidativna aktivnost, lidokain, bupivakain, ropivakain, antioxidant activity, lidocaine, bupivacaine, ropivacaine
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 11 str.
• Numbering: Vol. 11, art. 1208843
• PID: 20.500.12556/RUL-186545
• UDC: 611
• ISSN on article: 2296-2646
• DOI: 10.3389/fchem.2023.1208843
• COBISS.SI-ID: 156180483
• Publication date in RUL: 10.09.2026

Record is a part of a journal

• Title: Frontiers in chemistry
• Shortened title: Front. chem.
• Publisher: Frontiers Media
• ISSN: 2296-2646
• COBISS.SI-ID: 1647919

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: antioksidativna aktivnost, lidokain, bupivakain, ropivakain

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0012
• Name: Molekulske simulacije, bioinformatika in načrtovanje zdravilnih učinkovin

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0043
• Name: Molekularni mehanizmi razvoja in delovanja skeletne mišice