TY - JOUR AB - SP600125 is a classic inhibitor of c‑Jun‑N‑terminal kinase (JNK) that is widely used in numerous medicinal studies, but its administration regimen has yet to be optimized. In the present study, intraperitoneal (i.p.) and intragastric (i.g.) injections of 15 mg/kg SP600125 was performed in mice to compare the inhibitory effect against JNK signalling in cholestasis induced by α‑naphthylisothiocyanate (ANIT). SP600125 at a dose of 15 mg/kg administered by i.p. substantially decreased ANIT‑induced liver injury as observed by biochemical and histopathological examinations. The adaptation of bile acid synthesis was inhibited in the A‑SP‑i.p. group compared with that in the A‑SP‑i.g. group, as indicated by the expression analysis of CYP7A1 and CYP8B1. The transcription of the pro‑inflammatory factors IL‑6, IL‑1β, ICAM‑1 and IL‑10 supported the differential toxic responses. Western blot analysis revealed that JNK signalling activated by ANIT was inhibited more markedly in the A‑SP‑i.p. group than in the A‑SP‑i.g. group. The peak concentration and the AUC0‑24 of SP600125 in the A‑SP‑i.p. group were 5‑fold and 1.56‑fold higher, respectively, compared with those in the A‑SP‑i.g. group. These data indicated that i.p. administration of SP600125 produced a high plasma exposure profile, which directly determined its efficacy of blocking the JNK signalling. This effect of SP600125 on the JNK pathway may provide an optimized design for future in vivo investigations. AD - Department of Pharmacology, Medical School of Ningbo University, Ningbo, Zhejiang 315211, P.R. China Department of Basic Nutrition, Ningbo College of Health Sciences, Ningbo, Zhejiang 315100, P.R. China AU - Zheng,Xiuting AU - Dai,Manyun AU - Xu,Gangming AU - Chang,Liming AU - Yang,Julin AU - Liu,Aiming DA - 2020/12/01 DO - 10.3892/ijmm.2020.4742 EP - 2279 IS - 6 JO - Int J Mol Med KW - JNK SP600125 administration route inflammation cholestasis PY - 2020 SN - 1107-3756 1791-244X SP - 2271 ST - Inhibition of inflammation by SP600125 in cholestatic liver injury is dependent on the administration‑based exposure profile T2 - International Journal of Molecular Medicine TI - Inhibition of inflammation by SP600125 in cholestatic liver injury is dependent on the administration‑based exposure profile UR - https://doi.org/10.3892/ijmm.2020.4742 VL - 46 ER -