Sargassum horneri extract attenuates high-dose acetaminophen-induced hepatotoxicity by enhancing the antioxidant activity and inhibiting acetaminophen activation in the mouse liver.

Abstract

Sargassum horneri is an edible brown seaweed used as traditional medicine in various East Asian countries, such as China and Korea. Its therapeutic effects, including antioxidant and anti-inflammatory activities, have been reported in animal models of respiratory diseases and allergic disorders. However, its specific effects on liver health remain ambiguous. Therefore, in this study, we aimed to examine the effects of S. horneri extract (SHE) on acetaminophen (APAP)-induced hepatotoxicity, a common clinical cause of drug-induced liver injury. SHE-pretreated male mice were injected with a high dose of APAP. SHE alleviated APAP-induced liver injury and inhibited lipid peroxidation and glutathione (GSH) depletion. It also enhanced the hepatic total antioxidant capacity in APAP-treated mice, exhibiting direct radical scavenging activity against APAP-induced oxidative stress. Levels of the hepatic antioxidant enzymes, superoxide dismutase-1/2 and GSH peroxidase 1, were unaffected by SHE; however, catalase levels decreased by APAP were restored by the extract. Protein levels of the APAP-metabolizing enzymes, uridine 5'-diphospho-glucuronosyltransferase 1a6, sulfotransferase 1a1, GSH S-transferase a1, cytochrome P450 (Cyp)-1a2, Cyp2e1, and Cyp3a, were unaffected; however, Cyp1a activity was reduced by SHE. Plasma concentrations of APAP-GSH and APAP-cysteine conjugates were reduced by SHE in APAP-treated mice, indicating that SHE alleviates APAP hepatotoxicity by inhibiting Cyp1a-mediated metabolic activation of APAP. In conclusion, our results suggest that the increase in cellular antioxidant capacity and inhibition of APAP bioactivation are possible mechanisms underlying the hepatoprotective effects of SHE against high-dose APAP-induced acute liver injury.