Local anaesthetics or their combination with morphine and/or magnesium sulphate are toxic for equine chondrocytes and synoviocytes in vitro.

Abstract

BACKGROUND: Chondrotoxic effects of local anaesthetics are well reported in humans and some animal species but knowledge on their toxic effects on synoviocytes or equine chondrocytes or the effects on cellular production of inflammatory cytokines is limited. The purpose of this study was to evaluate the in vitro effects of local anaesthetics, morphine, magnesium sulphate (MgSO) or their combinations on cell viability and pro-inflammatory cytokine gene expression of equine synoviocytes and chondrocytes. Equine synoviocytes and cartilage explants harvested from normal joints in a co-culture system were exposed to mepivacaine (4.4 mg/ml), bupivacaine (2.2 mg/ml), morphine (2.85 mg/ml) and MgSO(37 mg/ml) alone or each local anaesthetic plus morphine or MgSOor both together. Chondrocyte and synoviocyte cell viability was assessed by CellTiter-Glo Luminescent Cell Viability Assay. Synoviocyte gene expression of IL-1β, IL-6 or TNF-α was measured and compared using the ∆∆CT method. RESULTS: Morphine alone, MgSOalone or their combination did not alter cell viability or the expression of IL-1β, IL-6 or TNF-α. However, local anaesthetics alone or in combination with morphine and/or MgSOreduced cell viability and increased the gene expression of IL-1β, IL-6 or TNF-α. Single short exposure to local anaesthetics is toxic to both chondrocytes and synoviocytes and their combination with morphine and/or MgSOenhanced the cytotoxic effects. CONCLUSIONS: This in vitro study gives further evidence of the absence of cytotoxic effects of morphine alone, MgSOalone or their combination on normal articular tissues. However, local anaesthetics alone or in combination with morphine and/or MgSOhave cytotoxic effects on equine articular tissues.