Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942012000200008
Brazilian Journal of Anesthesiology
Scientific Article

Análise do potencial citotóxico agudo da bupivacaína e bupivacaína em excesso enantiomerico de 50% (S75-R25) incorporadas a microesferas sobre o nervo ciático de ratos

Analysis of the acute cytotoxic potential of bupivacaine and 50% enantiomeric excess bupivacaine (S75-R25) incorporated into microspheres in rat sciatic nerves

Pedro Paulo Tanaka; Maria Fernanda Torres; Sergio Bernardo Tenorio

Downloads: 0
Views: 618

Resumo

JUSTIFICATIVA E OBJETIVOS: A duração do efeito dos anestésicos locais (AL) pode ser ampliada pela sua incorporação aos sistemas de liberação prolongada como microesferas. No entanto, a possibilidade de que os sistemas de liberação prolongada de AL sejam neurotóxicos não tem recebido a devida atenção na literatura. Este estudo teve o objetivo de investigar os efeitos de microesferas de ácido poliláctico-co-glicólico puras, preenchidas com bupivacaína em excesso enantiomérico de 50% ou com bupivacaína (BP), assim como os efeitos da bupivacaína em excesso enantiomérico de 50% em nervo ciático de ratos Wistar. MÉTODO: Os ratos foram alocados em quatro grupos de acordo com o tempo de avaliação (dois, quatro, seis e oito dias) e denominados conforme a solução injetada sobre o nervo ciático: microsferas com bupivacaína em excesso enantiomérico de 50% (MBE), microesferas com bupivacaína (MB); microesferas puras (MP) e bupivacaína em excesso enantiomérico de 50% (BE). RESULTADOS: Nos cortes histológicos semifinos observou-se distribuição regular homogênea nas fibras de colágeno no endoneuro e nenhuma alteração degenerativa dos axônios ou das bainhas de mielina foi constatada. Nos cortes ultrafinos foram observados axônios mielinizados e fibras de Remak de aspecto normal com axoplasma apresentando distribuição homogênea de neurofilamentos e microtúbulos. A análise histomorfométrica dos axônios não revelou diferença significativa entre os diâmetros dos axônios dos grupos estudados.

Palavras-chave

ANESTÉSICOS, ANESTÉSICOS, ANESTÉSICOS, ANESTÉSICOS, ANIMAL

Abstract

BACKGROUND AND OBJECTIVES: The duration of Local Anesthetic (LA) effects can be expanded by its incorporation into systems of sustained release microspheres. However, the possibility that LA sustained release systems are neurotoxic has not received due attention in literature. The objective of this study was to investigate the effects of pure microspheres of poly(lactic-co-glycolic acid), filled with 50% enantiomeric excess bupivacaine or bupivacaine (BP), as well as the effects of 50% enantiomeric excess bupivacaine in the sciatic nerve of Wistar rats. METHODS: The rats were allocated into four groups according to the evaluation time (two, four, six, and eight days) and nominated according to the injected solution on the sciatic nerve: Microspheres with 50% Enantiomeric excess Bupivacaine (MEB), Microspheres with Bupivacaine (MB), Pure Microspheres (PM), and 50% Enantiomeric excess Bupivacaine (EB). RESULTS: In semi-fine histologic sections, no regular homogeneous distribution of collagen fibers in the endoneurium or degenerative changes of axons and myelin sheaths were observed. In ultrathin sections, we found myelinated axons and normal Remak fibers with axoplasm showing homogeneous distribution of neurofilaments and microtubules. Histomorphometric analysis of axons revealed no significant difference between the axon diameters of the studied groups.

Keywords

Anesthetics, Bupivacaine, Microscopy, Microscopy, Microspheres, Rats, Stereoisomerism

References

Kalichman MW, Moorhourse DF, Powell HC. Relative neural toxicity of local anesthetics. J Neuropathol Exp Neurol. 1993;52:234-240.

Dyhre H, Soderberg L, Bjorkman S. Local anesthetics in lipid-depot formulations: Neurotoxicity in relation to duration of effect in a rat model. Reg Anesth Pain Med. 2006;31:401-408.

Araujo DR, Fraceto LF, Braga AFA, Paula E. Sistemas de liberação controlada com bupivacaína racêmica (S50-R50) e mistura enantiomérica de bupivacaína (S75-R25): Efeitos da complexação com ciclodextrinas no bloqueio do nervo ciático em camundongos. Rev Bras Anestesiol. 2005;55:316-328.

Araujo DR, Pinto LM, Braga AFA, Paulo E. Formulações de anestésicos locais de liberação prolongada: Aplicações terapêuticas. Rev Bras Anestesiol. 2003;53:663-671.

Simonetti MPB, Valinetti EA, Ferreira FMC. Evaluation of the local anesthetic activity of S(-) bupivacaine: experimental study in vivo in the rat sciatic nerve. Rev Bras Anestesiol. 1997;47:425-434.

Tanaka PP, Estebe JP, Campor R. Preparation, characterization and in vitro evaluation of 50% enantiomeric excess bupivacaine (S75-R25)-loaded microespheres. Rev Bras Anestesiol. 2008;58:15-22.

Oliveira RM. Analise comparativa entre microesferas, microesferas de bupivacaína em excesso enatiomérico de 50%, microeesferas de bupivacaína e bupivacaína em excesso enatiomerico de 50%: estudo em vivo após bloqueio do nervo ciático em ratos. .

Estebe JP, Myers RR. Amitriptyline Neurotoxicity: Dose-related pathology after topical application to rat sciatic nerve. Anesthesiol. 2004;100:1519-1525.

Mrak RE. The big eye in the 21st century: The role of electrón microscopy in modern diagnostic neuropathology. J Neuropathol Exp Neurol. 2002;61:1027-1039.

Uchino H, Matumura Y, Megishi T. Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats. Brit J Cancer. 2005;93:678-687.

Blanco MD, Bernardo MV, Gomez C. Bupivacaine-loaded comatrix formed by albumin microspheres included in a poly(lactide-co-glycolide) film: in vivo biocompatibility and drug release studies. Biomat. 1999;20:1919-1924.

Matey L, Luzzati V, Villegas GM. Order-disorder phenomena in myelinated nerve sheaths: IV. The disordering effects of high levels of local anesthetics on rat sciatic and optic nerves. J Mol Biol. 1992;226:535-545.

Song L, Xiao H, Yank H. Peripheral anti-hyperalgesic effect and neurotoxicologic screening of amitriptyline and bupivacaine on sciatic nerve blockade chronically on neuropathic pain in rats. Chin J Repar Reconst Surg. 2009;23:827-831.

Cavanagh JB. Reactions of neurons and Schwann cells to injury. Nervous System, Muscle and Eyes. 1990:533-543.

Summers BA, Cummings JF, Lahunta A. Diseases of the peripheral nervous system. Veterinary Pathology. 1995:402-501.

Sanchez M, Bondan EF, Lallo MA. Marcação imuno-histoquímica da resposta macrofágica e astrocitária no tronco encefálico de ratos Wistar submetidos ao modelo gliotóxico do brometo de etídio e tratados com ciclofosfamida. Arq Neuro-psiquiatria. 2006;64:787-793.

Le Coree P, Rytting JH, Gajan V. In vitro controlled release kinetics of local anaesthetics from poly(D, L-lactide) and poly(lactideco-glycolide) microspheres. J Microencapsul. 1997;14:243-255.

5dd54b2e0e88259a6ec8fca6 rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections