Differential cytotoxic properties of drugs used for intra-articular injection on human chondrocytes

Stueber, Thomas; Karsten, Jan; Stoetzer, Carsten; Leffler, Andreas

doi:10.1097/eja.0000000000000121

Cited by 21 publications

(15 citation statements)

References 32 publications

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“…Stueber et al incubated a monolayer of human cartilage cell line for 1 hour with a bupivacaine concentration range of 10 and 500 μM, morphine, dexamethasone, or S‐ketamine . With regard to bupivacaine compared to a control, they found bupivacaine to be chondrotoxic in a dose‐dependent manner, shown by an increase of annexin V and propidium iodide‐positive cells; however, a statistical analysis was not reported in this study.…”

Section: Resultscontrasting

confidence: 57%

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Chondrotoxic Effects of Local Anesthetics on Human Knee Articular Cartilage: A Systematic Review

Jayaram¹,

Kennedy

Yeh

et al. 2019

PM&R

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Objective To review the current literature on the effects of intraarticular local anesthetics on human knee articular cartilage. Literature Survey PubMed; MEDLINE; SCOPUS; PEDro; CINAHL databases (1/1990‐06/1/2018) were searched for local anesthetic effects on human knee articular cartilage. Methodology Sixteen studies met the inclusion criteria, with outcome measures assessing chondrocyte viability, morphology, and histology. A systematic review was performed using PRISMA guidelines. Synthesis Seven studies were identified evaluating lidocaine, with five of them demonstrating statistically significant chondrotoxic effects. Fourteen studies examined bupivacaine, with all but one study demonstrating a chondrotoxic effect. Eight studies examined ropivacaine and found a dose‐dependent chondrotoxicity starting at 0.75%. Two studies evaluated levobupivacaine showing chondrotoxicity, with one study showing it to be more chondrotoxic than bupivacaine. One study looked at mepivacaine and showed it to have more chondrotoxicity than ropivacaine. When studied the chondrotoxicity was found to be both dose and time dependent. Also, the addition of corticosteroids appeared to worsen the chondrotoxic effects. Conclusions Lidocaine, bupivacaine, ropivacaine, levobupivacaine, and mepivacaine were reported to have dose‐ and time‐dependent deleterious effects on chondrocytes that appeared to be made worse by the coadministration of corticosteroids. Ropivacaine at concentrations of 0.5% or less was found to be the least chondrotoxic anesthetic. Level of Evidence I

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Section: Resultscontrasting

confidence: 57%

“…A cumulative score of 7 was the highest achievable score. Three of the 16 studies achieved a score of 3 or less, whereas all other studies had either 4 or 5 points (Table ).…”

Section: Methodsmentioning

confidence: 99%

Chondrotoxic Effects of Local Anesthetics on Human Knee Articular Cartilage: A Systematic Review

Jayaram¹,

Kennedy

Yeh

et al. 2019

PM&R

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“…However, results are not transferable to human studies because of differences in physiological structure and sensitivity (15,16). Another study was performed with commercial cell lines rather than animal tissues (31). However, as these lines do not contain microenvironments, including ECM, and only represent one type cell, they are known to lose their original phenotypic and genotypic characteristics (1,10,13,1).…”

Section: Discussionmentioning

confidence: 99%

Effect of naproxen on proliferation and differentiation of primary cell cultures isolated from human cartilage tissue

Karaarslan

Batmaz²,

Yılmaz

et al. 2018

Exp Ther Med

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Non-steroidal anti-inflammatory drugs (NSAIDs) that are applied through oral, injectable or topical routes have been widely used in painful and inflammatory musculoskeletal diseases. The current study aimed to determine whether naproxen, an aryl acetic acid derivative with analgesic and anti-inflammatory effects, has a toxic effect on human chondrocytes. Samples containing monolayer primary chondrocyte cultures were prepared following resection from osteochondral tissues obtained from patients with gonarthrosis. Cell viability, toxicity and proliferation and levels of stage-specific embryonic antigen-1, a precursor to human prechondrocytes, were evaluated spectrophotometrically. The results from the untreated control group were compared with those of the study groups, where naproxen was administered in varying doses (1–1,000 µM). Surface morphologies of the cells were compared using inverted light and environmental scanning electron microscopy. Treatment groups were compared by analysis of variance with Tukey's honest difference post hoc test. P<0.01 was considered to indicate a statistically significant difference. The research revealed significant changes to proliferation and differentiation of chondrocytes in all treatment groups (P<0.01). Naproxen was demonstrated to suppress chondrocyte proliferation and differentiation, which may be an important factor to consider when prescribing this medication to patients.

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“…Only a few antibiotics, including the glycopeptide group of antibacterial agents and the quinolone group, were evaluated in terms of the chondrotoxicity in the cytotoxic studies (1, 7,10,14,15,[19][20][21][23][24][25]42,43,44).…”

Section: █ Discussionmentioning

confidence: 99%

Evaluation of the effect of daptomycin, a glycopeptide agent, on intact intervertebral disc tissue

Kaplan¹,

Yılmaz²,

Karaarslan³

et al. 2018

Turkish Neurosurgery

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AIM: To evaluate the effects of pre-and intra-operatively administered daptomycin (DAP) on the intact human primary intervertebral disc tissue cells. MATERIAL and METHODS: Primary cell cultures were established using tissues obtained through decompressive laminectomy, traumatic intervertebral disc herniation excision, and posterior transpedicular stabilization. Non-drug-administered samples were used as a control group. The samples treated with DAP formed the study group. Molecular assays for proliferation and gene expression were performed. The obtained data were evaluated statistically, and results with a value of p<0.05 were accepted as significant. RESULTS: While no reduction was observed in the proliferation, the gene expression of intact intervertebral disc tissue cells was time-dependently decreased compared to the control group, and these results were reported to be statistically significant. CONCLUSION: This study observed the effect that a pharmaceutical preparation, which was used on intervertebral disc tissue before and after the operation, had on normal, healthy, and intact tissue. It concludes that alterations in the expression of genes involved in the anabolic and/or catabolic process, even in adjacent healthy tissue, may slow down the healing process of the damaged tissue or cause undesired cell differentiation.

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Differential cytotoxic properties of drugs used for intra-articular injection on human chondrocytes

Abstract: Morphine and dexamethasone showed no cytotoxic effects in our study and might thus be better alternatives to the clinically frequently applied bupivacaine. S-ketamine induced an intensive dose-dependent cytotoxic effect and should probably be avoided for intra-articular injection.

Cited by 21 publications

References 32 publications

Chondrotoxic Effects of Local Anesthetics on Human Knee Articular Cartilage: A Systematic Review

Chondrotoxic Effects of Local Anesthetics on Human Knee Articular Cartilage: A Systematic Review

Effect of naproxen on proliferation and differentiation of primary cell cultures isolated from human cartilage tissue

Evaluation of the effect of daptomycin, a glycopeptide agent, on intact intervertebral disc tissue

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