Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1016/j.bjane.2013.07.006
Brazilian Journal of Anesthesiology
Scientific Article

Evaluation of genotoxicity induced by repetitive administration of local anaesthetics: an experimental study in rats

Avaliação da genotoxicidade induzida pela administração repetida de anestésicos locais: um estudo experimental em ratos

Gisele Alborghetti Nai; Mariliza Casanova de Oliveira; Graziela de Oliveira Tavares; Laís Fabrício Fonseca Pereira; Nádia Derli Salvador Lemes Soares; Patrícia Gatti Silva

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Abstract

BACKGROUND AND OBJECTIVE: Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. METHODS: 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0 mg/kg); group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. RESULTS: The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (p < 0.0001). A significant difference in the number of micronuclei was observed between the cyclophosphamide group and all local anaesthetic groups (p = 0.0001), but not between the negative control group and the local anaesthetic groups (p > 0.05). CONCLUSION: No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated.

Keywords

Anaesthesia, Genotoxicity, Mutagenicity tests, Micronucleus tests, Prilocaine

Resumo

JUSTIFICATIVA E OBJETIVOS: Estudos anteriores sobre os efeitos de alguns anestésicos locais sugeriram que esses agentes podem causar alterações genéticas. No entanto, esses agentes não são testados para genotoxicidade relacionada à administração repetida. O objetivo deste estudo foi avaliar o potencial genotóxico de anestésicos locais após repetidas administrações. MÉTODOS: 80 ratos Wistar machos foram alocados em: grupo A - 16 ratos receberam injeção por via intraperitoneal (IP) de cloridrato de lidocaína a 2%; grupo B - 16 ratos receberam injeção IP com mepivacaína a 2%; grupo C - 16 ratos receberam injeção IP de articaína a 4%; grupo D - 16 ratos receberam injeção IP de prilocaína a 3% (6 mg kg-1); grupo E - oito ratos receberam injeção subcutânea em dose única de ciclofosfamida; grupo F - oito ratos receberam injeção IP com solução salina. Oito ratos dos grupos de A a D receberam uma dose única de anestésico no Dia 1 da experiência; os ratos restantes foram dosados uma vez por dia durante cinco dias. RESULTADOS: A mediana do número de micronúcleos nos grupos com anestésicos locais expostos por um ou cinco dias variou de 0 a 1; no grupo exposto à ciclofosfamida foi de 10 e no grupo controle negativo no primeiro e quinto dias foi de 1 e 0, respectivamente (p < 0,0001). Uma diferença significativa foi observada no número de micronúcleos entre o grupo ciclofosfamida e todos os grupos com anestésicos locais (p = 0,0001), mas não entre o grupo controle negativo e os grupos com anestésicos locais (p > 0,05). CONCLUSÃO: Nenhum efeito de genotoxicidade foi observado após a exposição repetida a qualquer um dos anestésicos locais avaliados.

Palavras-chave

Anestesia, Genotoxicidade, Testes de mutagenicidade, Testes para micronúcleos, Prilocaína

References

Moore PA, Hersh EV. Local anesthetics: pharmacology and toxicity. Dent Clin North Am.. ;54:599-587.

Mariano RC, Santana SI, Coura GS. Análise comparativa do efeito anestésico da lidocaína 2% e da prilocaína 3%. Revista Brasileira de Cirurgia e Implantodontia - BCI.. ;7:19-15.

Jastak JT, Yagiela JA. Vasoconstritors and local anesthesia: a review and rationale for use. J Am Dent Assoc.. ;107:623-630.

Smith MT. The mechanism of benzene-induced leukemia: a hypothesis and speculations on the causes of leukemia. Environ Health Perspect.. ;104:1225-1219.

Duan JD, Jeffrey AM, Williams GM. Assessment of the medicines lidocaine, prilocaine, and their metabolites, 2,6dimethylaniline and 2-methylaniline, for DNA adduct formation in rat tissues. Drug Metab Dispos J.. ;8:1470-1475.

Flores M, Yamaguchi UM. Micronucleus test: an evaluation for genotoxic screening. J Health Res.. ;1:337-340.

Fenech M, Holland N, Chang WP. The HUman MicroNucleus Project - an international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. Mutat Res.. ;428:271-283.

MacGregor JT, Heddle JA, Hite M. Guidelines for the conduct of micronucleus assays in mammalian bone marrow erythrocytes. Mutat Res.. ;189:103-112.

Tolbert PE, Shy CM, Allen JW. Micronuclei and other nuclear anomalies in buccal smears: methods development. Mutat Res.. ;271:77-69.

Evans HJ. Historical perspectives on the development of the in vitro micronucleus test: a personal view. Mutat Res.. ;392:10-5.

Ramírez A, Saldanha PH. Análise crítica de grupos controle no teste de micronúcleo na mucosa bucal. Genet Mol Biol.. ;21:140.

Perusse R, Goulet JP, Turcotte JY. Contraindications to vasoconstrictors in dentistry: part I. Oral Surg Oral Med Oral Pathol.. ;74:686-679.

Schneider LE, do Amaral VS, Dihl RR. Assessment of genotoxicity of lidocaine, prilonest and septanest in the drosophila Wing-Spot test. Food Chem Toxicol.. ;47:208-205.

Hagiwara M, Watanabe E, Barrett JC. Assessment of genotoxicity of 14 chemical agents used in dental practice: ability to induce chromossome aberrations in Syrian hamster embryo cells. Mutat Res.. ;603:120-111.

Nakamura K, Kido H, Morimoto Y. Prilocaine induces apoptosis in osteoblastic cells. Can J Anaesth.. ;46:476-482.

Preston RJ, Williams GM. DNA-reactive carcinogens: mode of action and human cancer hazard. Crit Rev Toxicol.. ;35:683-673.

Leuschner J, Leblanc D. Studies on the toxicological profile of the local anaesthetic articaine. Arzneimittelforschung.. ;49:132-126.

Snoeck M. Articaine: a review of its use for local and regional anesthesia. Local Reg Anesth.. ;5:33-23.

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