The Potency of Cytotoxic Mechanisms of Local Anesthetics in Human Chondrocyte Cells

Local anesthetics are commonly used in various clinical settings for both prevention and symptom relief. Numerous clinical studies have demonstrated that intra-articular injections of local anesthetics achieve high success rates in orthopedic practices. However, several widely used local anesthetics, including bupivacaine, lidocaine, and ropivacaine, have been shown to exhibit toxicity to chondrocytes, with the underlying mechanisms of chondrotoxicity remaining poorly understood. In this study, we aimed to investigate the cytotoxic effects of local anesthetics, specifically focusing on the consequences of a single intra-articular injection in human chondrocyte cells. Our results reveal that lidocaine, levobupivacaine, bupivacaine, and ropivacaine induced cell death, characterized by the induction of apoptosis and the suppression of cellular proliferation. These effects were mediated through mechanisms involving oxidative stress, mitochondrial dysfunction, and autophagy pathways. We found that the toxic effects of local anesthetics were concentration-dependent, with lidocaine exhibiting the lowest cytotoxicity among the tested agents in TC28a cells. Notably, bupivacaine and levobupivacaine displayed significant cytotoxic effects related to apoptosis, cellular proliferation, reactive oxygen species generation, mitochondrial membrane potential depolarization, and autophagy in human chondrocyte cells. Our findings not only support existing clinical studies but also highlight potential targets for developing protective agents to mitigate serious side effects associated with their use in orthopedic practices.