title: Local neurotoxicity and myotoxicity evaluation of cyclodextrin complexes of bupivacaine and ropivacaine.
abstract: 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-β-cyclodextrin (HP-β-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-β-CD (BVC(HP-β-CD) and RVC(HP-β-CD)).
  
  
  METHODS
  Schwann cell viability was assessed by determination of mitochondrial dehydrogenase 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 (BVC(HP-β-CD) or RVC(HP-β-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.
authors: Department of Biochemistry, Institute of Biology, State University of Campinas, SP, Brazil. cscereda@gmail.com
authors: Cintia Maria Saia
authors: CM
authors: Cereda
authors: Giovana Radomille
authors: GR
authors: Tofoli
authors: Luiz Gabriel
authors: LG
authors: Maturana
authors: Amauri
authors: A
authors: Pierucci
authors: Lazaro Alessandro Soares
authors: LA
authors: Nunes
authors: Michelle
authors: M
authors: Franz-Montan
authors: Alexandre Leite Rodrigues
authors: AL
authors: de Oliveira
authors: Sarah
authors: S
authors: Arana
authors: Daniele Ribeiro
authors: DR
authors: de Araujo
authors: Eneida
authors: E
authors: de Paula
mesh_terms: D000577:Amides / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002045:Bupivacaine / Q000737:chemistry / Q000633:toxicity*; D002478:Cells, Cultured; D003505:Cyclodextrins / Q000737:chemistry / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D008297:Male; D009135:Muscular Diseases / Q000139:chemically induced / Q000175:diagnosis / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D000077212:Ropivacaine; D012584:Sciatic Nerve / Q000187:drug effects* / Q000473:pathology*
chemical_list: D000577:Amides; D003505:Cyclodextrins; D000077212:Ropivacaine; D002045:Bupivacaine