TY - JOUR
T1 - S100A11 mediates the protective effects of edaravone dexborneol on docetaxel-induced cognitive impairment in rats by inhibiting the MAPK signaling pathway
AU - Liu, Ping
AU - Jia, Jiantao
AU - Lu, Yinliang
AU - Tang, Hanmin
AU - Gao, Chengyi
AU - Han, Suxia
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/11
Y1 - 2025/11
N2 - Cognitive impairment is a common side effect of docetaxel (DTX)-based chemotherapy. The novel neuroprotective agent edaravone dexborneol (ED) was found to alleviate the adverse phenotype caused by DTX. However, the underlying mechanism remains unexplored. By analyzing mRNA-sequencing data, we noticed that the expression of S100 calcium-binding protein A11 (S100A11), a protector of the nervous system, was decreased in DTX-treated rats with cognitive damage, but ED administration reversed the trend. Therefore, we speculated that S100A11 might be involved in the protective effects of ED on DTX-induced cognitive impairment. Sprague-Dawley rats were intraperitoneally injected with DTX to induce cognitive impairment, followed by intraperitoneal injection of ED after DTX induction. The results showed that ED treatment mitigated cognitive impairment caused by DTX. Next, adenoviruses carrying sequences encoding S100A11 were given to rats receiving DTX treatment. S100A11 overexpression alleviated cognitive dysfunction of DTX-treated rats, as evidenced by the decreased escape latency and swimming distance, and the increased number of platform crossings. Mechanically, S100A11 overexpression inhibited neuronal apoptosis by inactivating the MAPK signaling pathway. Further rescue experiments showed that S100A11 knockdown reversed the defensive role of ED in DTX-induced neuronal damage. In conclusion, ED ameliorates cognitive dysfunction caused by DTX by upregulating the S100A11 expression and subsequently inactivating the MAPK signaling pathway.
AB - Cognitive impairment is a common side effect of docetaxel (DTX)-based chemotherapy. The novel neuroprotective agent edaravone dexborneol (ED) was found to alleviate the adverse phenotype caused by DTX. However, the underlying mechanism remains unexplored. By analyzing mRNA-sequencing data, we noticed that the expression of S100 calcium-binding protein A11 (S100A11), a protector of the nervous system, was decreased in DTX-treated rats with cognitive damage, but ED administration reversed the trend. Therefore, we speculated that S100A11 might be involved in the protective effects of ED on DTX-induced cognitive impairment. Sprague-Dawley rats were intraperitoneally injected with DTX to induce cognitive impairment, followed by intraperitoneal injection of ED after DTX induction. The results showed that ED treatment mitigated cognitive impairment caused by DTX. Next, adenoviruses carrying sequences encoding S100A11 were given to rats receiving DTX treatment. S100A11 overexpression alleviated cognitive dysfunction of DTX-treated rats, as evidenced by the decreased escape latency and swimming distance, and the increased number of platform crossings. Mechanically, S100A11 overexpression inhibited neuronal apoptosis by inactivating the MAPK signaling pathway. Further rescue experiments showed that S100A11 knockdown reversed the defensive role of ED in DTX-induced neuronal damage. In conclusion, ED ameliorates cognitive dysfunction caused by DTX by upregulating the S100A11 expression and subsequently inactivating the MAPK signaling pathway.
KW - Cognitive impairment
KW - Docetaxel
KW - Edaravone dexborneol
KW - S100 calcium-binding protein A11
KW - The MAPK signaling pathway
UR - https://www.scopus.com/pages/publications/105013126259
U2 - 10.1016/j.taap.2025.117504
DO - 10.1016/j.taap.2025.117504
M3 - 文章
C2 - 40780535
AN - SCOPUS:105013126259
SN - 0041-008X
VL - 504
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
M1 - 117504
ER -