The chondrotoxic and apoptotic effects of levobupivacaine and bupivacaine on the rabbit knee joint

Çevik, Osman; Gergin, Özlem Öz; Yildiz, Karamehmet; Bayram, Adnan; Canöz, Özlem; Halıcı, Mehmet; Baran, Münevver; Yay, Arzu Hanım; Polat, Sait

doi:10.1016/j.bjane.2018.06.008

Cited by 1 publication

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References 25 publications

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“…On the other hand, comparisons between bupivacaine and levobupivacaine have had mixed results. While bupivacaine is generally known to be one of the most chondrotoxic local anesthetics [ 16 , 22 ], levobupivacaine has been shown to be more chondrotoxic [ 11 ], less chondrotoxic [ 9 ], or having similar effects on chondrocyte viability as bupivacaine [ 19 ]. Further studies are required to clarify the reasons for these differences; however, this was not the focus of the current study.…”

Section: Discussionmentioning

confidence: 99%

“…The ability of local anesthetics to induce chondrocyte death through apoptosis has previously been demonstrated [ 6 , 9 , 14 ]. However, studies on whether this chondrotoxicity is through the intrinsic or extrinsic pathway of apoptosis are sparse.…”

Section: Discussionmentioning

confidence: 99%

“…They are considered to be less toxic than bupivacaine while having similar potency and duration of action [ 3 , 8 , 24 ]. While this may be true for systemic and cardiac toxicity, both levobupivacaine and ropivacaine have demonstrated chondrotoxicity, especially at high doses and with prolonged exposure [ 9 , 14 , 15 , 25 ]. The cytotoxic effects of local anesthetics appear to occur mainly through mitochondrial damage, which then leads to apoptosis or necrosis depending on the dose and period of time that the cells are exposed to the drug [ 14 , 17 , 18 , 42 ].…”

mentioning

confidence: 99%

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<i>In vitro</i> chondrotoxicity of bupivacaine, levobupivacaine and ropivacaine and their effects on caspase activity in cultured canine articular chondrocytes

et al. 2023

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Bupivacaine, levobupivacaine and ropivacaine are potent, long acting, amide-type local anesthetics that have several clinical applications including intra-articular administration. The objectives of this study were to evaluate their in vitro effects on cell viability and caspase activity to elucidate whether they activate the extrinsic or intrinsic pathways of apoptosis in canine articular chondrocytes.Chondrocytes in monolayer culture were treated with culture medium as the control, or with 0.062% (0.62 mg/mL) bupivacaine, 0.062% levobupivacaine, and 0.062% ropivacaine for 24 hr. Cell viability was evaluated using the live/dead, 3-(4,5-dimehylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), and Cell Counting Kit-8 (CCK-8) assays. Evaluation of caspase-3, caspase-8, and caspase-9 activity was performed using colorimetric assays. The MTT and CCK-8 assays were used to evaluate the effect of caspase inhibitors on local anesthetic chondrotoxicity. All three local anesthetics decreased chondrocyte viability after 24 hr (P ˂ 0.001). Apoptosis was induced through both the extrinsic and intrinsic pathways.Bupivacaine increased caspase-3, caspase-8, and caspase-9 activity (P ˂ 0.001). Levobupivacaine increased caspase-3 (P = 0.03) while ropivacaine did not significantly upregulate activity for all three caspases. Caspase inhibition did not suppress bupivacaine chondrotoxicity whereas inhibition of caspase-8 and caspase-9 decreased ropivacaine chondrotoxicity and mildly attenuated levobupivacaine chondrotoxicity. In summary, the level of chondrotoxicity, the type of caspase activated, the level of caspase activation, and the response to caspase inhibitors was dependent on the type of local anesthetic.Therefore, ropivacaine may be a safer choice for intra-articular administration compared to levobupivacaine and bupivacaine.

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