Acetaminophen

Acetaminophen (APAP) overdose is the leading cause of acute liver failure in the northern hemisphere. While historical research focused on the liver, recent evidence shows direct APAP toxicity in brain tissue at high doses, independent of liver failure. Paradoxically, low doses of APAP appear neuroprotective. This review provides a comprehensive update on APAP’s hepatic toxicity and a thorough examination of both toxic and beneficial effects in the brain, highlighting a previously underappreciated dual role.

Fig. 1 Effect of Different Concentrations of APAP on Primary Culture of Glial Cells. (Ghanem CI, et al., 2016)

This review discusses the roles of microRNAs, long noncoding RNAs, and circular RNAs in acetaminophen (APAP) hepatotoxicity. At therapeutic doses, APAP is safe, but overdose or co‑administration with alcohol or other xenobiotics can cause severe liver injury. Noncoding RNAs are increasingly recognized as modulators of APAP metabolism, the progression of toxicity, and subsequent liver regeneration. The authors highlight the emerging evidence linking ncRNAs to these processes, suggesting potential biomarkers or therapeutic targets for acetaminophen‑induced liver injury.

Fig. 2 MicroRNAs that are known to modulate acetaminophen metabolism in animal models (miR-122, miR-125b, and miR-22) and in cell (hepatocytes and HepaRG) cultures (miR-27b and miR-375). (Chowdhary V, et al., 2021)