0023-6152

AA00697606

7388809

Baricitinib (BCT) is a Janus kinase (JAK) inhibition medicine, which has been used in the treatment of several self–limiting immune diseases, including the pneumonia caused by COVID–19, rheumatoid arthritis, and alopecia areata etc. Researches show that BCT has significant impact on the mammalian immune system. However, the effects of BCT on aquatic organisms remain unclear. This study utilized the Japanese medaka (Oryzias latipes) to investigate the effects on the JAK/STAT signaling pathway and the neurobehavioral toxicity alterations induced by a 96–h Baricitinib exposure at the concentrations of 0, 0.05, 0.5, and 5 mg/L. After exposure, behavioral tests were conducted, and tissue samples of spleens and brains were collected and tested to evaluate the alterations of protein levels. The results showed that there were significant alterations in key proteins of the JAK/STAT pathway (JAK1, STAT1, STAT3, SOCS3, and SOCS8) in the spleen of medaka, with distinct sex–specific patterns between male and female individuals. The serotonin turnover rate (5–HIAA/5–HT) in the brain of male medaka was significantly reduced in the high BCT concentration group (5 mg/L) after BCT exposure. However, for female medaka, it did not change significantly in any exposure groups. Furthermore, results of behavioral assessment showed that BCT exposure significantly affected the behavioral activities and exploratory behavior of Japanese medaka. In general, the results suggested that BCT has significant effects the JAK/STAT signaling pathway as it has been to the mammalian animals. The changes of behavioral traits and brain neurotransmitter levels indicated a potential neurobehavioral influence of BCT on fish. People should pay more attention on the disposal of immunomodulatory medicines regarding to their potential adverse impacts on aquatic organisms.