Protection afforded by pre- or post-treatment with 4-phenylbutyrate against liver injury induced by acetaminophen overdose in mice

Combination of tauroursodeoxycholic acid and N‐acetylcysteine exceeds standard treatment for acetaminophen intoxication

“…The hepatic metabolism of APAP occurs rapidly after drug intake. Typically, in mice, depletion of GSH and development of oxidative stress are evident 1‐2 hours following APAP overdose with increased ALT levels after 6 hours which peak at 24 hours, and severe centrilobular necrosis with hepatocyte degeneration 6 hours after the APAP injection . In line with these findings, we observed a substantial increase in ALT and AST levels and extensive necrotic lesions 24 hours after APAP overdose.…”

“…Our results with TUDCA are also in line with Shimizu et al., who reported the therapeutic efficacy of 4‐phenylbutyrate (4‐PBA), a chemical chaperone like TUDCA, after APAP overdose in mice. However, they did not compare to NAC monotherapy and did not investigate the combined therapy with NAC and the mechanisms of 4‐PBA …”

“…12 APAP toxicity is associated with the accumulation of misfolded proteins causing endoplasmic reticulum (ER) stress. 9,13,14 ER stress activates a cellular adaptation programme, the unfolded protein response (UPR) that aims at restoring cellular homeostasis by repressing global translation and transcription of specific targets. However, when ER stress sustains, UPR activation can result in apoptosis through CHOPinduced attenuation of Bcl2 expression.…”

Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity

“…Among its known pharmacological effects, 4-PBA modulates the function of transcription factors associated with ER-stress, including JNK and XBP1 (105). A recent article evaluated the protective properties of 4-PBA when given prior or after toxic administration of APAP in mice (106). 4-PBA decreased drastically hepatic DNA fragmentation induced by APAP; however, the mechanism was unclear and did not involve Xbp1 mRNA splicing or JNK phosphorylation.…”

Preparation of hydrophilic C60(OH)10/2-hydroxypropyl-β-cyclodextrin nanoparticles for the treatment of a liver injury induced by an overdose of acetaminophen

“…An APAP overdose induced liver injury model was prepared according to the method reported by Ishituka et al [29]. Male 7-9 week-old C57BL6 mice (Japan SLC, Inc., Shizuoka, Japan) were fasted overnight, but had free access to water prior to the experiments.…”