title: In vitro exposure of human fibroblasts to local anaesthetics impairs cell growth.
abstract: Lidocaine, bupivacaine or ropivacaine are used routinely to manage perioperative pain. Sparse data exist evaluating the effects of local anaesthetics (LA) on fibroblasts, which are involved actively in wound healing. Therefore, we investigated the effects of the three LA to assess the survival, viability and proliferation rate of fibroblasts. Human fibroblasts were exposed to 0·3 mg/ml and 0·6 mg/ml of each LA for 2 days, followed by incubation with normal medium for another 1, 4 or 7 days (group 1). Alternatively, cells were incubated permanently with LA for 3, 6 or 9 days (group 2). Live cell count was assessed using trypan blue staining. Viability was measured by the tetrazolium bromide assay. Proliferation tests were performed with the help of the colorimetric bromodeoxyuridine assay. Production of reactive oxygen species (ROS) was determined, measuring the oxidation of non-fluorescent-2,7'-dichlorofluorescin. Treatment of cells with the three LA showed a concentration-dependent decrease of live cells, mitochondrial activity and proliferation rate. Group arrangement played a significant role for cell count and proliferation, while exposure time influenced viability. Among the analysed LA, bupivacaine showed the most severe cytotoxic effects. Increased production of ROS correlated with decreased viability of fibroblasts in lidocaine- and bupivacaine-exposed cells, but not upon stimulation with ropivacaine. This study shows a concentration-dependent cytotoxic effect of lidocaine, bupivacaine and ropivacaine on fibroblasts in vitro, with more pronounced effects after continuous incubation. A possible mechanism of cell impairment could be triggered by production of ROS upon stimulation with lidocaine and bupivacaine.
authors.affiliation: Department of Cranio-Maxillofacial Surgery, University Hospital of Zurich Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Fedder
authors.forename: B
authors.initials: B
authors.lastname: Beck-Schimmer
authors.forename: J
authors.initials: J
authors.lastname: Aguirre
authors.forename: M
authors.initials: M
authors.lastname: Hasler
authors.forename: B
authors.initials: B
authors.lastname: Roth-Z'graggen
authors.forename: M
authors.initials: M
authors.lastname: Urner
authors.forename: S
authors.initials: S
authors.lastname: Kalberer
authors.forename: A
authors.initials: A
authors.lastname: Schlicker
authors.forename: G
authors.initials: G
authors.lastname: Votta-Velis
authors.forename: J M
authors.initials: JM
authors.lastname: Bonvini
authors.forename: K
authors.initials: K
authors.lastname: Graetz
authors.forename: A
authors.initials: A
authors.lastname: Borgeat
mesh_terms: D000577:Amides / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002045:Bupivacaine / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077212:Ropivacaine
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D017382:Reactive Oxygen Species; D000077212:Ropivacaine; D008012:Lidocaine; D002045:Bupivacaine
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