Brazilian Journal of Anesthesiology
https://app.periodikos.com.br/journal/rba/article/doi/10.1016/j.bjane.2015.01.006
Brazilian Journal of Anesthesiology
Scientific Article

Comparative effects of vitamin C on the effects of local anesthetics ropivacaine, bupivacaine, and lidocaine on human chondrocytes

Efeitos comparativos de vitamina C sobre os efeitos dos anestésicos locais ropivacaína, bupivacaína e lidocaína em condrócitos humanos

Jun Tian; Yan Li

Downloads: 2
Views: 992

Abstract

BACKGROUND: Intra-articular injections of local anesthetics are commonly used to enhance post-operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra-articular local anesthetic have raised concerns. OBJECTIVES: The study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics - ropivacaine, bupivacaine and lidocaine - on human chondrocytes. METHODS: The chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500 µM was determined by LIVE/DEAD assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species. RESULTS: On exposure to the local anesthetics, chondrotoxicity was found in the order ropivacaine < bupivacaine < lidocaine. Vitamin C effectively improved the reduced chondrocyte viability and decreased the raised apoptosis levels following exposure to anesthesia. At higher doses, vitamin C was found efficient in reducing the generation of reactive oxygen species and as well down-regulate the expressions of caspases 3 and 9. CONCLUSIONS: Vitamin C was observed to effectively protect chondrocytes against the toxic insult of local anesthetics ropivacaine, bupivacaine and lidocaine.

Keywords

Chondrocytes, Vitamin C, Local anesthetics, Ropivacaine, Bupivacaine, Lidocaine

Resumo

JUSTIFICATIVA: Injeções de anestésicos locais por via intra-articular são comumente usadas para melhorar a analgesia no período pós-operatório de cirurgia ortopédica como artroscopia. No entanto, relatos recentes de complicações graves devido ao uso de anestésico local por via intra-articular causou preocupações. OBJETIVOS: O objetivo do estudo foi avaliar o uso de vitamina C para reduzir os efeitos adversos dos anestésicos mais comumente usados (ropivocaína, bupivacaína e lidocaína) sobre condrócitos humanos. MÉTODOS: A viabilidade dos condrócitos após a exposição à bupivacaína a 0,5% ou ropivacaína a 0,75% ou lidocaína a 1,0% e/ou vitamina C em doses de 125, 250 e 500 µM foi determinada pelo ensaio Vivo/Morto e coloração com anexina V. Os níveis de expressão das caspases 3 e 9 foram avaliados com o uso de anticorpos pela técnica Western blotting. Citometria de fluxo foi feita para analisar a geração de espécies reativas ao oxigênio. RESULTADOS: Na exposição aos anestésicos locais, condrotoxicidade foi encontrada na seguinte ordem: ropivacaína < bupivacaína < lidocaína. A vitamina C efetivamente melhorou a redução da viabilidade dos condrócitos e diminuiu os níveis elevados de apoptose após a exposição à anestesia. Em doses mais altas, a vitamina C foi eficiente para reduzir a geração de espécies reativas ao oxigênio e assim regular negativamente a expressão das caspases 3 e 9. CONCLUSÕES: Observamos que a vitamina C foi eficaz na proteção dos condrócitos contra a agressão tóxica dos anestésicos locais ropivacaína, bupivacaína e lidocaína.

Palavras-chave

Condrócitos, Vitamina C, Anestésicos locais, Ropivacaína, Bupivacaína, Lidocaína

References

Piper SL, Kim HT. Comparison of ropivacaine and bupivacaine toxicity in human articular chondrocytes. J Bone Joint Surg Am.. 2008;90:986-91.

Piper SL, Kramer JD, Kim HT. Effects of local anesthetics on articular cartilage. Am J Sports Med.. 2011;39:2245-53.

Dragoo JL, Braun HJ, Kim HJ. The in vitro chondro-toxicity of single-dose local anesthetics. Am J Sports Med.. 2012;40:794-9.

Petty DH, Jazrawi LM, Estrada LS. Glenohumeral chon-drolysis after shoulder arthroscopy: case reports and review of the literature. Am J Sports Med.. 2004;32:509-15.

Kamath R, Strichartz G, Rosenthal D. Cartilage toxicity from local anesthetics. Skeletal Radiol.. 2008;37:871-3.

Gomoll AH, Yanke AB, Kang RW. Long-term effects of bupi-vacaine on cartilage in a rabbit shoulder model. Am J Sports Med.. 2009;37:72-7.

Solomon DJ, Navaie M, Stedje-Larsen ET. Gleno-humeral chondrolysis after arthroscopy: a systematic review of potential contributors and causal pathways. Arthroscopy.. 2009;25:1329-42.

Anderson SL, Buchko JZ, Taillon MR. Chondrolysis of the glenohumeral joint after infusion of bupivacaine through an intraarticular pain pump catheter: a report of 18 cases. Arthroscopy.. 2010;26:451-61.

Hepburn Walsh P, Mulhall KJ. The chondrotoxicity of local anaesthetics: any clinical impact?. Joint Bone Spine.. 2011;78:438-40.

McLure HA, Rubin AP. Review of local anaesthetic agents. Minerva Anestesiol.. 2005;71:59-74.

Karpie JC, Chu CR. Lidocaine exhibits dose- and time-dependent cytotoxic effects on bovine articular chondrocytes in vitro. Am J Sports Med.. 2007;35:1621-7.

Baker JF, Walsh PM, Byrne DP. In vitro assessment of human chondrocyte viability after treatment with local anaes-thetic, magnesium sulphate or normal saline. Knee Surg Sports Traumatol Arthrosc.. 2011;19:1043-6.

Park J, Sutradhar BC, Hong G. Comparison of the cyto-toxic effects of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes. Vet Anaesth Analg.. 2011;38:127-33.

Lo IK, Sciore P, Chung M. Local anesthetics induce chon-drocyte death in bovine articular cartilage disks in a dose- and duration-dependent manner. Arthroscopy.. 2009;25:707-15.

Zink W, Graf BM. Local anesthetic myotoxicity. Reg Anesth Pain Med.. 2004;29:333-40.

Perez-Castro R, Patel S, Garavito-Aguilar ZV. Cytotoxic-ity of local anesthetics in human neuronal cells. Anesth Analg.. 2009;108:997-1007.

Dragoo JL, Korotkova T, Kim HJ. Chondrotoxicity of low pH, epinephrine, and preservatives found in local anesthetics containing epinephrine. Am J Sports Med.. 2010;38:1154-9.

Fedder C, Beck-Schimmer B, Aguirre J. In vitro exposure of human fibroblasts to local anaesthetics impairs cell growth. Clin Exp Immunol.. 2010;162:280-8.

Costouros JG, Dang AC, Kim HT. Inhibition of chondro-cyte apoptosis in vivo following acute osteochondral injury. Osteoarthritis Cartilage.. 2003;11:756-9.

Takahashi T, Yamamoto H, Ogawa Y. Role of apoptosis inhibition in various chondrocyte culture systems. Int J Mol Med.. 2003;11:299-303.

Rao A, Johnston TR, Harris AH. Inhibition of chondrocyte and synovial cell death after exposure to commonly used anes-thetics chondrocyte apoptosis after anesthetics. Am J Sports Med.. 2014;42:50-8.

Gaby AR. Natural approaches to epilepsy. Altern Med Rev.. 2007;12:9-24.

Gasiorowski A, Dutkiewicz J. Weight training and appropri-ate nutrient supplementation as an alternative method to pharmacological treatment in rehabilitation of post-myocardial infarction patients. Ann Agric Environ Med.. 2012;19:333-8.

Padayatty SJ, Katz A, Wang Y. Vitamin C as an antiox-idant: evaluation of its role in disease prevention. J Am Coll Nutr.. 2003;22:18-35.

Okma-Keulen P, Hopman-Rock M. The onset of generalized osteoarthritis in older women: a qualitative approach. Arthritis Rheum.. 2001;45:183-90.

Termine JD. American Society for Bone and Mineral Research. Bone matrix proteins and the mineralization process. 1990.

Peterkofsky B. Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr.. 1991;54:1135S-40S.

Kipp DE, McElvain M, Kimmel DB. Scurvy results in decreased collagen synthesis and bone density in the guinea pig animal model. Bone.. 1996;18:281-8.

Sahni S, Hannan MT, Gagnon D. Protective effect of total and supplemental vitamin C intake on the risk of hip fracture - a 17-year follow-up from the Framingham Osteoporosis Study. Osteoporos Int.. 2009;20:1853-61.

Breu A, Eckl S, Zink W. Cytotoxicity of local anesthet-ics on human mesenchymal stem cellsin vitro. Arthroscopy.. 2013;29:1676-84.

Lu HF, Sue CC, Yu CS. Diallyl disulfide (DADS) induced apoptosis undergo caspase-3 activity in human bladder cancer T24 cells. Food Chem Toxicol.. 2004;42:1543-52.

Koyonos L, Yanke AB, McNickle AG. A randomized, prospective, double-blind study to investigate the effective-ness of adding DepoMedrol to a local anesthetic injection in postmeniscectomy patients with osteoarthritis of the knee. Am J Sports Med.. 2009;37:1077-82.

Dragoo JL, Korotkova T, Kanwar R. The effect of local anesthetics administered via pain pump on chondrocyte viabil-ity. Am J Sports Med.. 2008;36:1484-8.

Chu CR, Izzo NJ, Papas NE. In vitro exposure to 0. 5% bupivacaine is cytotoxic to bovine articular chondrocytes. Arthroscopy.. 2006;22:693-9.

Gomoll AH, Kang RW, Williams JM. Chondrolysis after continuous intra-articular bupivacaine infusion: an experimen-tal model investigating chondrotoxicity in the rabbit shoulder. Arthroscopy.. 2006;22:813-9.

Farkas B, Kvell K, Czompoly T. Increased chondrocyte death after steroid and local anesthetic combination. Clin Orthop Relat Res.. 2010;468:3112-20.

Park CJ, Park SA, Yoon TG. Bupivacaine induces apoptosis via ROS in the Schwann cell line. J Dent Res.. 2005;84:852-7.

Grishko V, Xu M, Wilson G. Apoptosis and mitochondrial dysfunction in human chondrocytes following exposure to lido-caine, bupivacaine, and ropivacaine. J Bone Joint Surg Am.. 2010;92:609-18.

5dcd9a7d0e88255457bf58f1 rba Articles
Links & Downloads

Braz J Anesthesiol

Share this page
Page Sections