Maltol Improves APAP-Induced Hepatotoxicity by Inhibiting Oxidative Stress and Inflammation Response via NF-κB and PI3K/Akt Signal Pathways

Abstract

Maltol, a food-flavoring agent and Maillard reaction product formed during the processing of red ginseng (Panax ginseng, C.A. Meyer), has been confirmed to exert a hepatoprotective effect in alcohol-induced oxidative damage in mice. However, its beneficial effects on acetaminophen (APAP)-induced hepatotoxicity and the related molecular mechanisms remain unclear. The purpose of this article was to investigate the protective effect and elucidate the mechanisms of action of maltol on APAP-induced liver injury in vivo. Maltol was administered orally at 50 and 100 mg/kg daily for seven consecutive days, then a single intraperitoneal injection of APAP (250 mg/kg) was performed after the final maltol administration. Liver function, oxidative indices, inflammatory factors—including serum alanine and aspartate aminotransferases (ALT and AST), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), liver glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) were measured. Results demonstrated that maltol possessed a protective effect on APAP-induced liver injury. Liver histological changes and Hoechst 33258 staining also provided strong evidence for the protective effect of maltol. Furthermore, a maltol supplement mitigated APAP-induced inflammatory responses by increasing phosphorylated nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase α/β (IKKα/β), and NF-kappa-B inhibitor alpha (IκBα) in NF-κB signal pathways. Immunoblotting results showed that maltol pretreatment downregulated the protein expression levels of the B-cell-lymphoma-2 (Bcl-2) family and caspase and altered the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in a dose-dependent manner. In conclusion, our findings clearly demonstrate that maltol exerts a significant liver protection effect, which may partly be ascribed to its anti-inflammatory and anti-apoptotic action via regulation of the PI3K/Akt signaling pathway.

Comparative Studies on the Hepatoprotective Effect of White and Coloured Rice Bran Oil against Acetaminophen‐Induced Oxidative Stress in Mice through Antioxidant‐ and Xenobiotic‐Metabolizing Systems

“…APAP overdose-induced liver hepatotoxicity is a well-known drug-induced liver injury. It is the most common cause of acute liver failure in several countries, replacing viral hepatitis [ 36 ]. Extensive oxidative stress is a characteristic of APAP hepatotoxicity during APAP metabolism.…”

Effects of Dietary Maltol on Innate Immunity, Gut Health, and Growth Performance of Broiler Chickens Challenged With Eimeria maxima

“…Our in vitro studies showed that maltol played a role as an immune modulator during inflammatory responses. Maltol also influences the anti-oxidant activity ( 22 ) by scavenging free radicals generated during oxidative stress ( 20 ). Oxidative stress incurred during an inflammatory response may trigger the overproduction of reactive oxygen species, which can form a vicious circle resulting in tissue damage in intestinal epithelia and liver tissues ( 36 ).…”

“…In our previous study ( 19 ), dietary feeding of the Bacillus subtilis 1781 strain induced the alteration of chicken gut metabolites which was associated with the growth- and immune-promoting effects of dietary B. subtilis 1781 strain in chickens. Among the highly altered gut metabolites, maltol was one of the significantly increased metabolites that we selected for further studies since maltol mediates various physiological functions associated with anti-oxidant ( 20 ) and anti-carcinogen ( 21 ) activities and reduces inflammatory responses ( 22 ).…”

MicroRNA-221/222 Mediates ADSC-Exosome-Induced Cardioprotection Against Ischemia/Reperfusion by Targeting PUMA and ETS-1

“…The AKT signaling pathway plays an essential role against I/R injury by regulating proapoptotic signals, inflammation and ROS ( Li Q. et al, 2019 ). Oxidative stress-induced cell apoptosis is due to AKT dysfunction and NFκB upregulation ( Wang et al, 2019 ). JNK/NFκB is involved in myocardial I/R-induced apoptosis ( Zhang et al, 2019 ).…”