Preclinical evidence 4
4 studies reported at therapy level; 4 evidence entries itemised.
MouseChemical/toxinC57BL/6Pre-treatment before paraquat challenge
Model: Paraquat-induced acute cardiac contractile dysfunction
Paraquat challenge impaired contractile function, deranged intracellular calcium handling and produced echocardiographic abnormalities together with raised RIP1, RIP3 and MLKL expression and reactive oxygen species overproduction. Necrostatin-1 pre-treatment prevented the cardiac contractile dysfun…
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MouseChemical/toxinC57BL/6MaleIntraperitoneal1.8 mg/kg in 2% dimethyl sulfoxide in phosphate-buffered sa…1 hour before D-galactosamine and lipopolysaccharide administration
Model: Fulminant hepatic failure induced by D-galactosamine 800 mg/kg with lipopolysaccharide 40 µg/kg
Necrostatin-1 attenuated the rise in RIP1 and RIP3 expression, phosphorylation and complex formation, markedly reduced mortality and serum alanine aminotransferase, and lowered HMGB1 and interleukin 33 release with reduced pattern recognition receptor signalling.
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MouseChemical/toxinC57BL/6 (H-2K) wild type, RIP3 knockout and NLRP3 knockoutMaleIntraperitoneal for inhibitors; concanavalin A intravenous, acetaminophen intraperitonealNecrostatin-1 1.65 per g body weight intraperitoneally; Z-I…Pretreatment before injury; a single dose of necrostatin-1s immediately before…
Model: Concanavalin A-induced autoimmune hepatitis and acetaminophen-induced acute liver injury in mice
RIP3 deletion was protective in both models. RIP1 inhibition with necrostatin-1 protected against acetaminophen injury with reduced NLRP3 inflammasome activation and sterile inflammation, but markedly exacerbated concanavalin A hepatitis with increased apoptosis, accelerated death and reduced survi…
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MouseChemical/toxinC57BL/6Pretreatment before concanavalin A or poly(I:C) challenge
Model: Concanavalin A-induced and polyinosinic-polycytidylic acid-induced acute hepatitis, with CCl4-induced liver injury as an additional model
Pretreatment with necrostatin-1 and/or PJ34 significantly protected mice against concanavalin A liver injury as judged by transaminases, and down-regulated hepatocyte-specific IL-33 expression. PJ34 also reduced liver injury and IL-33 after poly(I:C) but gave no protection in CCl4-induced injury.
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