Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt; Department of Ophthalmology and Micro-Technology, Yokohama City University, Yokohama, Japan.
Faculty of Medicine, Ain Shams University, Cairo, Egypt.
J Food Drug Anal. 2018 Apr;26(2S):S78-S87. doi: 10.1016/j.jfda.2017.11.004. Epub 2017 Dec 16.
Acetaminophen (paracetamol or APAP) is an analgesic and antipyretic drug that can induce oxidative stress-mediated hepatotoxicity at high doses. Several studies reported that antioxidant nutraceuticals, in particular phenolic phytochemicals from dietary food, spices, herbs and algae have hepatoprotective effects. Others, however, suggested that they may negatively impact the metabolism, efficacy and toxicity of APAP. The aim of this review is to discuss the pros and cons of the association of antioxidant nutraceuticals and APAP by reviewing the in vivo evidence, with particular reference to APAP pharmacokinetics and hepatotoxicity. Results from the murine models of APAP-induced hepatotoxicity showed amelioration of liver damage with nutraceuticals coadministration, as well as reductions in tissue markers of oxidative stress, and serum levels of hepatic enzymes, bilirubin, cholesterol, triglycerides and inflammatory cytokines. On the other hand, both increased and decreased APAP plasma levels have been reported, depending on the nutraceutical type and route of administration. For example, studies showed that repeated administration of flavonoids causes down-regulation of cytochrome P450 enzymes and up-regulation of uridine diphosphate glucuronosyltransferases (UGT). Moreover, nutraceuticals can alter the levels of APAP metabolites, such as mercapturate glucuronide, sulfate and cysteine conjugates. Overall, the reviewed in vivo studies indicate that interactions between APAP and nutraceuticals or plant foods exist. However, the majority of data come from animal models with doses of phytochemicals far from dietary ones. Human studies should investigate gene-diet interactions, as well as ethnic variability in order to clarify the pros and cons of co-administering antioxidant nutraceuticals and APAP.
对乙酰氨基酚（扑热息痛或 APAP）是一种镇痛和解热药物，大剂量使用会导致氧化应激介导的肝毒性。有几项研究报告称，抗氧化营养保健品，特别是来自饮食食品、香料、草药和藻类的酚类植物化学物质，具有肝保护作用。然而，其他人则认为它们可能会对 APAP 的代谢、疗效和毒性产生负面影响。本综述的目的是通过审查体内证据来讨论抗氧化营养保健品与 APAP 联合应用的利弊，特别是参考 APAP 药代动力学和肝毒性。APAP 诱导的肝毒性的小鼠模型的结果表明，营养保健品联合应用可改善肝损伤，同时降低组织氧化应激标志物和血清肝酶、胆红素、胆固醇、甘油三酯和炎症细胞因子水平。另一方面，据报道，根据营养保健品的类型和给药途径，APAP 的血浆水平会增加或降低。例如，研究表明，类黄酮的重复给药会导致细胞色素 P450 酶下调和尿苷二磷酸葡萄糖醛酸转移酶（UGT）上调。此外，营养保健品可以改变 APAP 代谢物的水平，如巯基尿酸盐、硫酸盐和半胱氨酸缀合物。总的来说，综述的体内研究表明 APAP 和营养保健品或植物性食物之间存在相互作用。然而，大多数数据来自远低于饮食剂量的动物模型。人类研究应调查基因-饮食相互作用以及种族差异，以阐明联合使用抗氧化营养保健品和 APAP 的利弊。
