Preclinical evidence 3
3 studies reported at therapy level; 3 evidence entries itemised.
MouseChemical/toxinC57BL/6JMalen = Not reported per group; zero of 12 mice died in the cisplat…Trametinib intraperitoneal; U0126 route not statedU0126 5 mg/kg twice weekly (7.5 and 15 mg/kg twice weekly c…Started after tumour engraftment (day 10 for U0126, day 17 for trametinib) and…
Model: Cisplatin-induced acute kidney injury; low-dose model of cisplatin 12.5 mg/kg once weekly for 4 weeks in mice bearing subcutaneous CMT167 KRAS-mutant lung carcinoma flank tumours, plus a short-term model of cisplatin 30 mg/kg on day 0 with sacrifice on day 3
U0126 significantly improved kidney function, acute tubular necrosis and tubular apoptosis and also reduced tumour weight and volume. Trametinib did not protect against acute kidney injury in the 4 week model but decreased tumour growth more than cisplatin and prolonged survival in the high-dose mo…
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RatIschaemia-reperfusionCerebral (MCAO/stroke)WistarMaleAt 0, 6 and 24 h following reperfusion
Model: Ophthalmic artery occluded for 2 h using the middle cerebral artery occlusion model, followed by reperfusion
U0126 attenuated the ischaemia-induced increase in endothelin-1 mediated vasoconstriction (151.0 plus or minus 22.0 per cent of 60 mM K versus 212.1 plus or minus 14.7 per cent in untreated) and improved acute retinal function (a-wave 668 plus or minus 73 microvolts versus 560 plus or minus 21 in u…
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MouseChemical/toxinSwiss Webster, C57Bl/10 and C57Bl/10ScCr (TLR4 null)MaleIntraperitoneal, dissolved in DMSO and diluted in PBS10 mg/kg30 minutes before oleic acid administration
Model: Acute lung injury induced by intratracheal instillation of trisoleate (oleic acid), 1.25 micromol in 0.05 mL (approximately 10 mg/kg), under isoflurane anaesthesia; intratracheal lipopolysaccharide 500 ng in 0.05 mL used as a comparator injury
Pretreatment with U0126 significantly reduced neutrophil migration, oedema, lipid body formation and IL-6 production in oleic acid challenged mice, with IL-1 the exception. Increased inflammation after oleic acid was not dependent on TLR4, since TLR4-null mice were not protected.
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