Protective effect of ISO-1 with inhibition of RIPK3 up-regulation and neutrophilic accumulation on acetaminophen-induced liver injury in mice

• A MIF antagonist, ISO-1, protected mice from acute acetaminophen (APAP)-induced liver injury. The effect of ISO-1 may be involved in the recover GSH depletion and inhibition up-regulation RIPK3 kinase following oxidative stress by APAP liver. As an additional on APAP-liver injury, inhibit development further expansion excessive neutrophilic responses. Overdose use (APAP) often occurs a severe its injury is lethal some cases. Macrophage migration inhibitory factor (MIF) expressed variety cells has multifunctional roles. However, role APAP-induced not been fully investigated. In this study, we investigated whether treatment with (S,R)-3-(4-hydroxyphenil)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), inhibitor, Acute was induced injection (300 mg/kg body weight). Mice were treated single ISO-1(15 weight) 1 h (h) before administration. Histological, biochemical molecular analyses performed 12 after remarkably improved histological findings mice. increases serum levels alanine aminotransferase (ALT), macrophage inflammatory protein-2 (MIP-2) inhibited ISO-1. addition, reduced increased number myeloperoxidase-staining that TUNEL-positive staining Up-regulation hepatic receptor interacting protein (RIPK)3 heat shock protein70 suppressed given These results provide evidence activity clinically effective for