Karakuş Seçil Azime, Saraçoğlu Ayten, Güler Eray Metin, Bozali Kübra, Önal Ceren, Bulun Yekbun, Gaszyński Tomasz, Ratajczyk Paweł, Saraçoğlu Kemal Tolga
Department of Anesthesiology and Reanimation, University of Health Sciences Turkey, Başakşehir Çam and Sakura City Hospital, Istanbul 34480, Türkiye.
Department of Anaesthesiology, University of Florida College of Medicine, Jacksonville 8th St W Florida, Gainesville, FL 32209, USA.
Biomedicines. 2025 Apr 29;13(5):1074. doi: 10.3390/biomedicines13051074.
Lidocaine (LIDO) toxicity is a critical concern in regional anesthesia, with no specific antidote currently available. While lipid emulsions are commonly used as rescue agents in cases of local anesthetic systemic toxicity (LAST), their efficacy is inconsistent, and their safety remains controversial. AmnioMax (AMX), a specialized cell culture medium enriched with growth factors and bioactive molecules, has the potential to offer cytoprotective effects. This study aims to investigate the therapeutic efficacy of AMX in mitigating lidocaine-induced cytotoxicity and to explore its protective mechanisms at the cellular level. Healthy colon cells (CCD-18Co) were used in this study. Four experimental groups were established as follows: control, LIDO, AMX, and LIDO + AMX. Cellular viability in the control group was set at 100%. LIDO was administered at concentrations ranging from 0.06 to 10%, AMX at 0.625-100%, and LIDO + AMX at 60% of the half-maximal effective concentration (EC) combined with LIDO (0.06-10%). Cells were incubated for 24 h, after which cellular viability, DNA damage, apoptosis, intracellular reactive oxygen species (iROS), intracellular calcium (Ca), mitochondrial membrane potential (MMP), and glutathione (GSH) were evaluated. : LIDO exposure led to a concentration-dependent decrease in viability compared to the control group ( < 0.001), while AMX significantly increased viability ( < 0.001). In the LIDO + AMX group, viability was also reduced ( < 0.001); however, cytotoxicity was significantly lower than in the LIDO group ( < 0.05). Both the LIDO and LIDO + AMX groups showed increased iROS levels, DNA damage, and apoptosis ( < 0.001), along with the decreased MMP and GSH levels ( < 0.001) compared to the control. However, in the LIDO + AMX group, iROS, DNA damage, and apoptosis were significantly lower than in the LIDO group ( < 0.01), MMP levels were increased ( < 0.001), and no significant difference was observed in GSH levels. AMX demonstrated cytoprotective effects against LIDO-induced cytotoxicity, suggesting its potential as an alternative therapeutic agent for LAST.
利多卡因(LIDO)毒性是区域麻醉中的一个关键问题,目前尚无特效解毒剂。虽然脂质乳剂通常被用作局部麻醉药全身毒性(LAST)病例的抢救药物,但其疗效并不一致,安全性也仍存在争议。AmnioMax(AMX)是一种富含生长因子和生物活性分子的特殊细胞培养基,具有提供细胞保护作用的潜力。本研究旨在探讨AMX减轻利多卡因诱导的细胞毒性的治疗效果,并在细胞水平上探索其保护机制。本研究使用了健康的结肠细胞(CCD-18Co)。设立了四个实验组如下:对照组、利多卡因组、AMX组和利多卡因+AMX组。对照组的细胞活力设定为100%。利多卡因的给药浓度范围为0.06%至10%,AMX为0.625%至100%,利多卡因+AMX为半数最大有效浓度(EC)的60%与利多卡因(0.06%至10%)联合使用。细胞孵育24小时后,评估细胞活力、DNA损伤、凋亡、细胞内活性氧(iROS)、细胞内钙(Ca)、线粒体膜电位(MMP)和谷胱甘肽(GSH)。与对照组相比,利多卡因暴露导致细胞活力呈浓度依赖性下降(<0.001),而AMX显著提高了细胞活力(<小0.001)。在利多卡因+AMX组中,细胞活力也降低了(<0.001);然而,细胞毒性明显低于利多卡因组(<0.05)。与对照组相比,利多卡因组和利多卡因+AMX组的iROS水平、DNA损伤和凋亡均增加(<0.001),同时MMP和GSH水平降低(<0.001)。然而,在利多卡因+AMX组中,iROS、DNA损伤和凋亡明显低于利多卡因组(<0.01),MMP水平升高(<0.001),GSH水平未观察到显著差异。AMX对利多卡因诱导的细胞毒性具有细胞保护作用,表明其作为LAST替代治疗药物的潜力。
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