Randelli Filippo, Mazzoleni Manuel G, Menon Alessandra, Fioruzzi Alberto, Henin Dolaji, Sommariva Michele, Gagliano Nicoletta
Hip Department (CAD), Gaetano Pini-CTO Orthopedic Institute, University of Milan, P-za Cardinal Ferrari 1, 20122 Milano, Italy.
Laboratory of Applied Biomechanics, Department of Biomedical Sciences for Health, Università Degli Studi di Milano, Via Mangiagalli 31, 20133 Milan, Italy.
Cells. 2025 Jun 27;14(13):988. doi: 10.3390/cells14130988.
Local anesthetics (LAs) are frequently administered via peritendinous ultrasound-guided injections for diagnostic and therapeutic purposes. Since in vitro studies have demonstrated LAs' tenotoxic effects, raising concerns about their safety in infiltrative treatments, and since lidocaine (LD) emerged as one of the most cytotoxic LAs, we analyzed apoptosis, oxidative stress, and collagen turnover pathways in human tenocytes treated with LD, as well as the possible protection from LD-induced injury elicited by antioxidant ascorbic acid (AA). Tenocytes from gluteal tendons were treated with 0.2 and 1 mg/mL LD, or left untreated (CT), and treated with 50 μg/mL or 250 μg/mL AA. Nuclear morphology, cytochrome c expression, and caspase 3 activation were analyzed to study the effect of LD on apoptosis. Heme Oxygenase 1 () mRNA and genes and proteins involved in collagen turnover were investigated using molecular approaches. Our results show that 0.2 and 1 mg/mL LD did not induce apoptosis and did not modify collagen synthesis and maturation. Conversely, increased collagen degradation was observed, and AA was not protective against oxidative stress induction in the presence of LD. Our findings suggest that LD does not affect the cell viability of tenocytes and that peritendinous LD injections are safe in this regard. LD-associated collagen degradation and the AA buffer effect are still debatable. Overall, our study contributes to clarifying the effect of LD on tenocytes' viability and ECM homeostasis and provides new additional information useful for the safe clinical application of this drug and for further analysis.
局部麻醉药（LAs）常用于经腱鞘周围超声引导注射，以达到诊断和治疗目的。由于体外研究已证明局部麻醉药具有腱毒性作用，引发了人们对其在浸润性治疗中安全性的担忧，且利多卡因（LD）是细胞毒性最强的局部麻醉药之一，因此我们分析了用LD处理的人肌腱细胞中的细胞凋亡、氧化应激和胶原周转途径，以及抗氧化剂抗坏血酸（AA）对LD诱导损伤的可能保护作用。将臀肌腱的肌腱细胞用0.2和1mg/mL的LD处理，或不进行处理（CT），并用50μg/mL或250μg/mL的AA处理。分析细胞核形态、细胞色素c表达和半胱天冬酶3激活情况，以研究LD对细胞凋亡的影响。采用分子方法研究血红素加氧酶1（）mRNA以及参与胶原周转的基因和蛋白质。我们的结果表明，0.2和1mg/mL的LD不会诱导细胞凋亡，也不会改变胶原的合成和成熟。相反，观察到胶原降解增加，并且在存在LD的情况下，AA对氧化应激诱导没有保护作用。我们的研究结果表明，LD不会影响肌腱细胞的细胞活力，在这方面腱鞘周围注射LD是安全的。LD相关的胶原降解和AA缓冲作用仍存在争议。总体而言，我们的研究有助于阐明LD对肌腱细胞活力和细胞外基质稳态的影响，并为该药物的安全临床应用和进一步分析提供新的有用信息。
