In vitro demonstration of herbal exacerbation of paracetamol-induced hepatotoxicity

Abstract

BackgroundParacetamol (acetaminophen) is one of the most accessible pharmaceutical analgesic and antipyretic agents. Similarly, traditional herbal medicines including Psoralea corylifolia, Astragalus propinquus and Atractylodes macrocephala have been used for centuries to treat cold and flu-like symptoms. As herbal medicines are ‘natural and safe’, likelihood of combination with over-the-counter pharmaceuticals is high. Paracetamol and herbal medicines are associated with many adverse effects, hepatotoxicity being a common complication. PurposeTo determine whether concomitant use of paracetamol with phytochemicals commonly found in herbal medicines, including psoralen, astragaloside IV (AST-IV) and atractylenolide I (ATR-I) may produce synergistic hepatotoxicity. MethodsParacetamol (0–50 mM), psoralen (0–1000 µM) and AST-IV and ATR-I (0–300 µM) were tested on a human hepatocellular carcinoma cell line (HepG2) individually and in combination. Interactions were determined using fixed concentrations of 200 µM psoralen with paracetamol (0 – 50 mM), and 10 mM paracetamol with AST-IV or ATR-I (0 – 300 µM). ResultsParacetamol and psoralen demonstrated significant concentration-dependent toxicity individually (P < 0.05), however AST-IV and ATR-I alone or in combination with each other had little effect (P > 0.05). Fixed 200 µM psoralen in 20 mM – 50 mM paracetamol had approximately 20% increase in cell death compared to paracetamol with no psoralen; thus, paracetamol and psoralen demonstrated increased toxicity through synergistic interactions (P < 0.01; CI < 1). ConclusionsThis study highlights the potential risks that herbal medicines can have on paracetamol-induced liver injury and may explain the underlying mechanisms where patients have developed liver failure and necrosis in the presence of low levels of paracetamol.