Inhibition of Chondrocyte and Synovial Cell Death After Exposure to Commonly Used Anesthetics

Rao, Allison J.; Johnston, Tyler; Harris, Alex H. S.; Smith, R. Lane; Costouros, John G.

doi:10.1177/0363546513507426

Cited by 38 publications

(38 citation statements)

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“…These effects were demonstrated by the increased chromatin condensation and nuclear fragmentation with enhanced cleavage of caspase-3, the appearance of a sub-G 0 /G 1 peak in the flow cytometry assay, and the increased percentage of apoptotic cells in the annexin V binding assay. The induction of apoptosis by LAs in chondrocytes has been reported by several studies using in vitro cellular models [1,11] . Recently, Grishko et al have suggested that a mitochondrial pathway is involved in LA-induced apoptosis, which is associated with mitochondrial dysfunction resulting from damage to the mitochondrial genome [11] .…”

Section: Wwwchinapharcom Lee Yj Et Almentioning

confidence: 78%

“…However, there are a number of reports concerning the toxic effects of LAs on cartilage and muscle [1,2] , in addition to the overt cartilage damage observed at the time of surgery. There is evidence supporting a chondrotoxic effect of LAs on articular chondrocytes from several recent studies that have demonstrated detrimental effects of LAs on chondrocyte viability and cartilage histology [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

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Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway

2016

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Aim: Intra-articular injection of local anesthetics (LAs) is a common procedure for therapeutic purposes. However, LAs have been found toxic to articular cartilage, and hyaluronan may attenuate this toxicity. In this study we investigated whether hyaluronan attenuated lidocaine-induced chondrotoxicity, and if so, to elucidate the underlying mechanisms. Methods: Human chondrocyte cell line SW1353 and newly isolated murine chondrocytes were incubated in culture medium containing hyaluronan and/or lidocaine for 72 h. Cell viability was evaluated using MTT assay. Cell apoptosis was detected with DAPI staining, caspase 3/7 activity assay and flow cytometry. Cell cycle distributions, ROS levels and mitochondrial membrane potential (ΔΨm) were determined using flow cytometry. The expression of p53 and p53-regulated gene products was measured with Western blotting. Results: Lidocaine (0.005%−0.03%) dose-dependently decreased the viability of SW1353 cells. This local anesthetic (0.015%, 0.025%) induced apoptosis, G 2 /M phase arrest and loss of ΔΨm, and markedly increased ROS production in SW1353 cells. Hyaluronan (50−800 µg/mL) alone did not affect the cell viability, but co-treatment with hyaluronan (200 µg/mL) significantly attenuated lidocaine-induced apoptosis and other abnormalities in SW1353 cells. Furthermore, co-treatment with lidocaine and hyaluronan significantly decreased the levels of p53 and its transcription targets Bax and p21 in SW1353 cells, although treatment with lidocaine alone did not significantly change these proteins. Similar results were obtained in ex vivo cultured murine chondrocytes. Conclusion: Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro through inhibiting the p53-dependent mitochondrial apoptotic pathway.

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Section: Wwwchinapharcom Lee Yj Et Almentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway

2016

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“…Previous meta-analyses have demonstrated that the single-dose IA morphine34, bupivacaine567, ropivacaine8, clonidine9 or the combination of morphine and bupivacaine1011 were effective in pain relief. However, it is commonly known that IA local anesthetics must be used cautiously due to the concern of chondrotoxicity12, especially for bupivacaine13141516171819, levobupivacaine131419, ropivacaine13141617, mepivacaine17 and lidocaine13161820.…”

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confidence: 99%

Analgesic effect and safety of single-dose intra-articular magnesium after arthroscopic surgery: a systematic review and meta-analysis

Zeng

Wei

et al. 2016

Sci Rep

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To examine the analgesic effect and safety of single-dose intra-articular (IA) magnesium (Mg) after arthroscopic surgery. Pubmed, Embase and Cochrane library were searched through in January 2016. Eight RCTs and eight experimental studies were included. The IA Mg exhibited a significantly lower pain score when compared with placebo (MD, −0.41, 95% CI, −0.78 to −0.05, p = 0.03). There was no significant difference between Mg and bupivacaine in terms of pain relief and the time to first analgesic request. Furthermore, statistically significant differences both in pain score (MD, −0.62, 95% CI, −0.81 to −0.42, p < 0.00001) and time to first analgesic request (MD, 6.25, 95% CI, 5.22 to 7.29, p < 0.00001) were observed between Mg plus bupivacaine and bupivacaine alone. There was no statistically significant difference among the various groups with respect to adverse reactions. Most of the included in vitro studies reported the chondrocyte protective effect of Mg supplementation. There were also two in vivo studies showing the cartilage protective effect of IA Mg. The single-dose IA Mg following arthroscopic surgery was effective in pain relief without increasing adverse reactions, and it could also enhance the analgesic effect of bupivacaine. In addition, Mg seemed to possess the cartilage or chondrocyte protective effect based on experimental studies.

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“…Grishko et al reported that caspase‐3 and caspase‐9 increase in human chondrocytes following LA exposure, which induced apoptosis of chondrocytes. Rao et al demonstrated that the LA increase the activity of caspase‐3 in chondrocytes, and the LA‐induced chondrocyte death was significantly reduced after treatment of pan‐caspase inhibitor (z‐vad‐fmk). That study reported that caspases play a potential role in LA induced chondrocyte death.…”

Section: Discussionmentioning

confidence: 99%

“…A few studies have investigated the possibility of avoiding LA‐induced chondrocyte death by using opioid injections instead of LA injections . One study suggested that apoptosis inhibition may be an effective strategy for minimizing chondrocyte death after exposure to LA . However, no study has suggested any other method of protecting chondrocytes from the adverse effects of LA.…”

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confidence: 99%

N‐acetyl cysteine protects cells from chondrocyte death induced by local anesthetics

Kim

Kang

Hah

et al. 2016

Journal Orthopaedic Research

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Local anesthetics (LA) are among the drugs most frequently used for musculoskeletal problems, in procedures ranging from diagnosis to postoperative pain control. Chondrocyte toxicity induced by LA is an emerging area of concern. The purpose of this study was to determine whether N-acetyl cysteine (NAC), an antioxidant, will exert cytoprotective effects against chondrocyte death induced by LA. Primary cultured human chondrocytes were used for this study. This study used control, NAC, LA, and NAC-LA groups. Cytotoxicity was induced in the LA subgroups and their paired NAC-LA subgroups through exposure to ropivacaine (0.075%), bupivacaine (0.05%), or lidocaine (0.2%) for 24 h. The NAC-LA subgroups were exposed to 10 mM NAC for 1 h, before LA exposure. These study groups were evaluated for rates of cell viability, apoptosis, necrosis, intracellular ROS production, and caspase-3/7 activity. Cell viability in all LA subgroups was significantly lower than in the control group (p < 0.001). Cell viability in the NAC-LA subgroups was significantly higher than in their paired LA subgroups (p < 0.001). In the LA subgroups, rates of apoptosis and necrosis, intracellular ROS production, and caspase-3/7 activity were significantly higher than in the control group (p ≤ 0.029). In the NAC-LA subgroups, rates of apoptosis and necrosis, intracellular ROS production, and caspase-3/7 activity were significantly lower than in their paired LA subgroups (p ≤ 0.023). These results indicate that N-acetyl cysteine, an antioxidant, has cytoprotective effects against LA-induced toxicity to chondrocytes in vitro. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:297-303, 2017.

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Inhibition of Chondrocyte and Synovial Cell Death After Exposure to Commonly Used Anesthetics

Abstract: Apoptosis inhibition may be an effective strategy in minimizing chondrocyte and synovial cell death after exposure to anesthetics. Further investigation is clinically warranted.

Cited by 38 publications

References 58 publications

Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway

Hyaluronan suppresses lidocaine-induced apoptosis of human chondrocytes in vitro by inhibiting the p53-dependent mitochondrial apoptotic pathway

Analgesic effect and safety of single-dose intra-articular magnesium after arthroscopic surgery: a systematic review and meta-analysis

N‐acetyl cysteine protects cells from chondrocyte death induced by local anesthetics

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