Small molecule drug intervention for chondrocytes is a valuable method for the treatment of osteoarthritis (OA). The 4‐octyl itaconate (OI) is a cellular derivative of itaconate with sound cell permeability and transformation rate. We attempted to confirm the protective role of OI in chondrocytes and its regulatory mechanism. We used lipopolysaccharide (LPS) to induce chondrocyte inflammation injury. After the OI treatment, the secretion and mRNA expression of Il‐6, Il‐10, Mcp‐1 and Tnf‐α were detected by ELISA and qPCR. The protective effect of OI on articular cartilage was further verified in surgical destabilization of the medial meniscus model of OA. Cell death and apoptosis were evaluated based on CCK8, LDH, Typan blue staining, Annexin V and TUNEL analyses. The small interfering RNAs were used to knockout the Nrf2 gene of chondrocytes to verify the OI‐mediated Nrf2 signalling pathway. The results revealed that OI protects cells from LPS‐induced inflammatory injury and attenuates cell death and apoptosis induced by LPS. Similar protective effects were also observed on articular cartilage in mice. The OI activated Nrf2 signalling pathway and promoted the stable expression and translocation of Nrf2 into the nucleus. When the Nrf2 signalling pathway was blocked, the protective effect of OI was significantly counteracted in chondrocytes and a mouse arthritis model. Both itaconate and its derivative (i.e., OI) showed important medical effects in the treatment of OA.

Ototoxicity refers to the pathological and functional impairments of auditory nervous system caused by the application of some therapeutic drugs. Although drug-induced hearing loss is not fatal, it will seriously damage the social and health-related quality of patients, with significant implications for careers, education and society. In children, even minor hearing loss can impede speech, language, cognition and social development, which can lead to poor academic performance and psychosocial functioning. 1-5 Worldwide, around 30 thousand children suffer from cytotoxic agents every year. Currently, there are more than 600 drugs having ototoxic properties, such as aminoglycoside antibiotics, platinum-based chemotherapy drugs, cyclic diuretics, macrolides and