Mito-TEMPO (MT) greatly attenuates the increase in ALT activities and reduces the areas of necrosis at both time points, indicating that the protection by Mito-TEMPO is sustained until at least 24 h post-APAP. Mito-Tempo could induce secondary apoptosis in the late phase of APAP hepatotoxicity. Mito-Tempo induces secondary apoptosis after APAP overdose by inhibition of RIP3[1].
In Vitro
Kinase Assay
Cell Assay
Animal Administration
Mice[1] Male C57BL/6J mice (8-12 weeks) and RIP3-deficient mice (C57BL/6N background) are used throughout the study. The mice are acclimated before experiments with free access to diet and water. Overnight-fasted mice (16-18 h) are treated i.p. with 300 mg/kg APAP dissolved in warm saline. Some mice are treated with 200 mg/kg APAP in experiments evaluating effect of RIP3 deficiency. A dose of 20 mg/kg Mito-Tempo dissolved in saline is administered i.p. 1.5 or 3 h after APAP. Some mice are subsequently treated (i.p.) with 10 mg/kg ZVD fmk dissolved in Tris-buffered saline or vehicle 2 h after APAP. To mimic the clinical care of APAP-overdose patients, some mice receive the antidote NAC (i.p., 500 mg/kg) at 1.5 or 3 h after APAP overdose[1].
References
[1]. Du K, et al. Mito-tempo protects against acute liver injury but induces limited secondary apoptosis during the late phase of acetaminophen hepatotoxicity. Arch Toxicol. 2018 Oct 15.
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