Acetaminophen (APAP)-induced liver injury in humans is associated with robust coagulation cascade activation and thrombocytopenia. However, it is not known whether coagulation-driven platelet activation participates in APAP hepatotoxicity. Here, we found that APAP overdose in mice caused liver damage accompanied by significant thrombocytopenia and accumulation of platelets in the liver. These c...

Gunn rats glucuronidate acetaminophen (APAP) at reduced rates and show increased susceptibility to APAP-induced hepatotoxicity. This defect is presumed to involve UDP-glucuronosyltransferase (UGT) 1A6, which is nonfunctional in Gunn rats, but it is currently unclear whether other 1A family members are also involved. In humans, two 1A isoforms are known to be active (1A6 and 1A9) but 1A6 form ha...

Previously, we reported that acetaminophen (APAP) showed selective toxicity towards melanoma cell lines. In the current study, we investigated further the role of tyrosinase in APAP toxicity in SK-MEL-28 melanoma cells in the presence of a short hairpin RNA (shRNA) plasmid, silencing tyrosinase gene. Results from tyrosinase shRNA experiments showed that APAP led to negligible toxicity in shRNA ...

Acetaminophen (APAP) and its conjugates (APAP-conj) are the major metabolites of phenacetin. To study their significance in the pathogenesis of analgesic nephropathy, their concentrations in the renal parenchyma were determined in conjunction with clearance measurements in 15 dogs with inulin as a reference marker. Particular attention was given to interpretation of the mechanisms responsible f...

Phospholipids are an important class of lipids that act as building blocks of biological cell membranes and participate in a variety of vital cellular functions including cell signaling. Previous studies have reported alterations in phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) metabolism in acetaminophen (APAP)-treated animals or cell cultures. However, little is known about ph...

BACKGROUND The long-term mortality of acetaminophen (APAP) poisoning has not yet been well studied; hence, we conducted this study to gain understanding of this issue. METHODS We conducted a nationwide population-based cohort study by identifying 3235 participants with APAP poisoning and 9705 participants without APAP poisoning in Taiwan between 2003 and 2012 in the Nationwide Poisoning Datab...

Nrf2, a member of the "cap 'n collar" group of transcription factors, is important for protecting cells against oxidative damage. We investigated its role in the detoxification of acetaminophen [N-acetyl-p-aminophenol (APAP)]-induced hepatotoxicity. When Nrf2 knockout (Nrf2(-/-)) and wild-type mice were given APAP by i.p. injection, the Nrf2(-/-) mice were highly susceptible to APAP treatment. ...

Acetaminophen (APAP) toxicity threatens human health due to increased mortality associated with its overdose. Doxycycline (DC) because of its properties such as antioxidant and anti-inflammatory can be a good therapeutic strategy to treat the acute toxicity induced by APAP. Male mice were divided to six groups in two periods of 3 and 24-h as normal saline, APAP 400 mg/kg, DC 100 mg/kg and group...

The role of protein glutathionylation in acetaminophen (APAP)-induced liver injury was investigated in this study. A single oral gavage dose of 150 or 300 mg/kg APAP in B6C3F1 mice produced increased serum alanine aminotransferase and aspartate aminotransferase levels and liver necrosis in a dose-dependent manner. The ratio of GSH to GSSG was decreased in a dose-dependent manner, suggesting tha...