Britza Susan M, Musgrave Ian F, Byard Roger W
Adelaide Medical School, The University of Adelaide, Adelaide 5005, South Australia, Australia.
Adelaide Medical School, The University of Adelaide, Adelaide 5005, South Australia, Australia; Forensic Science South Australia, Adelaide, South Australia 5000, Australia.
Leg Med (Tokyo). 2020 Nov;47:101740. doi: 10.1016/j.legalmed.2020.101740. Epub 2020 Jun 27.
Hepatotoxicity from paracetamol/acetaminophen has occasionally been reported at lower than expected doses. As herbal preparations may interact with pharmaceutical drugs the following in vitro study was undertaken to determine whether the toxic effects of paracetamol on liver cell growth in culture would be exacerbated by the addition of psoralen, a furanocoumarin compound that is present in Psoralea corylifolia, a common Chinese herb. The following study utilising a liver carcinoma cell line (HepG2) showed that Psoralea corylifolia was significantly toxic from 0.3 mg/ml to 5 mg/ml (p < 0.05), whereas paracetamol was not toxic below 50 mM (p = 0.0026). Interactions between previously non-toxic levels of 0.1 mg/ml of Psoralea corylifolia and increasing concentrations of paracetamol (0-50 mM), however, were observed, with a significant increase in toxicity compared to paracetamol alone (30% cell death vs. 72% cell death with Psoralea corylifolia). A significant synergistic interaction was observed at 40 mM paracetamol with 0.1 mg/ml of Psoralea (p = 0.038). This study has, therefore, shown significantly increased hepatotoxicity in cell cultures exposed to paracetamol when herbal compounds containing furanocoumarins were added. Fulminant acute liver failure occurring after the ingestion of low doses of paracetamol may not, therefore, always be due to an occult idiosyncratic response to paracetamol, but instead possibly to the combined effects of paracetamol and herbal preparations. Given the widespread use of both paracetamol and herbal preparations this possibility should be considered in cases of unexplained hepatic necrosis and liver failure that present for medicolegal investigation.
对乙酰氨基酚/醋氨酚导致的肝毒性偶尔会在低于预期剂量时被报道。由于草药制剂可能与药物发生相互作用，因此进行了以下体外研究，以确定补骨脂素（一种存在于常见中药补骨脂中的呋喃香豆素化合物）的添加是否会加剧对乙酰氨基酚对培养肝细胞生长的毒性作用。以下利用肝癌细胞系（HepG2）进行的研究表明，补骨脂在0.3毫克/毫升至5毫克/毫升时具有显著毒性（p < 0.05），而对乙酰氨基酚在50毫摩尔以下无毒（p = 0.0026）。然而，观察到之前无毒水平的0.1毫克/毫升补骨脂与浓度不断增加的对乙酰氨基酚（0 - 50毫摩尔）之间存在相互作用，与单独使用对乙酰氨基酚相比，毒性显著增加（细胞死亡率为30%，而补骨脂存在时为72%）。在40毫摩尔对乙酰氨基酚与0.1毫克/毫升补骨脂时观察到显著的协同相互作用（p = 0.038）。因此，这项研究表明，当添加含有呋喃香豆素的草药化合物时，暴露于对乙酰氨基酚的细胞培养物中的肝毒性显著增加。因此，低剂量对乙酰氨基酚摄入后发生的暴发性急性肝衰竭可能并不总是由于对乙酰氨基酚的隐匿性特异反应，而是可能由于对乙酰氨基酚和草药制剂的联合作用。鉴于对乙酰氨基酚和草药制剂的广泛使用，在因法医学调查而出现的不明原因肝坏死和肝衰竭病例中应考虑这种可能性。
