Local Neurotoxicity and Myotoxicity Evaluation of Cyclodextrin Complexes of Bupivacaine and Ropivacaine

Autor(es)

Saia Cereda, Cintia Maria ^[1] ; Tofoli, Giovana Radomille ^[2] ; Maturana, Luiz Gabriel ^[3] ; Pierucci, Amauri ^[3] ; Soares Nunes, Lazaro Alessandro ^[1] ; Franz-Montan, Michelle ^[1] ; Rodrigues de Oliveira, Alexandre Leite ^[4] ; Arana, Sarah ^[5] ; de Araujo, Daniele Ribeiro ^[6] ; de Paula, Eneida ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Dept Biochem, Inst Biol, Campinas, SP - Brazil

^[2] Univ Sao Francisco, Lab Mol Biol & Pharmacol, BR-12900000 Braganca Paulista, SP - Brazil

^[3] Fed Univ Jequitinhonha & Mucuri Valleys, Dept Basic Sci, Diamantina, MG - Brazil

^[4] Univ Estadual Campinas, Dept Anat Celular Biol Physiol & Biophys, Inst Biol, Campinas, SP - Brazil

^[5] Univ Estadual Campinas, Dept Histol & Embryol, Inst Biol, Campinas, SP - Brazil

^[6] Fed Univ ABC, Human & Nat Sci Ctr, Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ANESTHESIA AND ANALGESIA; v. 115, n. 5, p. 1234-1241, NOV 2012.
• Citações Web of Science: 23

Resumo

BACKGROUND: Bupivacaine (BVC) and ropivacaine (RVC) are local anesthetics widely used in surgical procedures. In previous studies, inclusion complexes of BVC or RVC in hydroxypropyl-beta-cyclodextrin (HP-beta-CD) increased differential nervous blockade, compared to the plain anesthetic solutions. In this study we evaluated the local neural and muscular toxicity of these new formulations containing 0.5% BVC or RVC complexed with HP-beta-CD (BVCHP-beta-CD and RVCHP-beta-CD). METHODS: Schwann cell viability was assessed by determination of mitochondrial dehydrogenese activity, and histopathological evaluation of the rat sciatic nerve was used to identify local neurotoxic effects (48 hours and 7 days after the treatments). Evaluations of serum creatine kinase levels and the histopathology of rat gastrocnemius muscle (48 hours after treatment) were also performed. RESULTS: Schwann cell toxicity evaluations revealed no significant differences between complexed and plain local anesthetic formulations. However, use of the complexed local anesthetics reduced serum creatine kinase levels 5.5-fold, relative to the plain formulations. The differences were significant at P < 0.05 (BVC) and P < 0.01 (RVC). The histopathological muscle evaluation showed that differences between groups treated with local anesthetics (BVC or RVC) and their respective complexed formulations (BVCHP-beta-CD or RVCHP-beta-CD) were significant (P < 0.05). CONCLUSIONS: We concluded that the new formulations presented a lower myotoxicity and a similar cytotoxic effect when compared to plain local anesthetic solutions. (Anesth Analg 2012;115:1234-41) (AU)

• Processo FAPESP: 07/55189-0 - Avaliação da citotoxidade e da neurotoxicidade local de anestésicos locais em formulações de liberação prolongada
• Beneficiário: Cíntia Maria Saia Cereda
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 06/00121-9 - Novas formulações de anestésicos locais de liberação controlada: do desenvolvimento ao teste clínico odontológico
• Beneficiário: Eneida de Paula
• Modalidade de apoio: Auxílio à Pesquisa - Temático