Association of antioxidant nutraceuticals and acetaminophen (paracetamol): Friend or foe?

Mohamed Abdel-Daim a,b, Abdelrahman Ibrahim Abushouk c, Raffaella Reggi d, Nagendra Sastry Yarla e, Maura Palmery d, Ilaria Peluso f,*

a Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt

b Department of Ophthalmology and Micro-Technology, Yokohama City University, Yokohama, Japan

c Faculty of Medicine, Ain Shams University, Cairo, Egypt

d Department of Physiology and Pharmacology “V. Erspamer”, “Sapienza” University of Rome, Italy

e Divisions of Biochemistry & Chemistry, City University of New York School of Medicine, 160 Convent Avenue, New York, NY 10031, USA

f Research Center for Food and Nutrition, Council for Agricultural Research and Economics, (CREA-AN), Rome, Italy

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 theymay negatively impact themetabolism, efficacy and toxicity of APAP. The aimof this review is to discuss the prosandconsof the associationofantioxidantnutraceuticalsandAPAPbyreviewingthe in vivo evidence, with particular reference to APAP pharmacokinetics and hepatotoxicity. Results fromthemurinemodels ofAPAP-inducedhepatotoxicity showedameliorationof 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 APAPmetabolites, such asmercapturate 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, aswell as ethnic variability in order to clarify the pros and cons of co-administering antioxidant nutraceuticals and APAP.