The Liver Protection Effects of Maltol, a Flavoring Agent, on Carbon Tetrachloride-Induced Acute Liver Injury in Mice via Inhibiting Apoptosis and Inflammatory Response

Abstract

The purpose of this research was to evaluate whether maltol could protect from hepatic injury induced by carbon tetrachloride (CCl4) in vivo by inhibition of apoptosis and inflammatory responses. In this work, maltol was administered at a level of 100 mg/kg for 15 days prior to exposure to a single injection of CCl4 (0.25%, i.p.). The results clearly indicated that the intrapulmonary injection of CCl4 resulted in a sharp increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities, tumor necrosis factor-α (TNF-α), irreducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB) and interleukin-1β (IL-1β) levels. Histopathological examination demonstrated severe hepatocyte necrosis and the destruction of architecture in liver lesions. Immunohistochemical staining and western blot analysis suggested an accumulation of iNOS, NF-κB, IL-1β and TNF-α expression. Maltol, when administered to mice for 15 days, can significantly improve these deleterious changes. In addition, TUNEL and Hoechst 33258 staining showed that a liver cell nucleus of a model group diffused uniform fluorescence following CCl4 injection. Maltol pretreatment groups did not show significant cell nuclear condensation and fragmentation, indicating that maltol inhibited CCl4-induced cell apoptosis. By evaluating the liver catalase (CAT), glutathione (GSH), superoxide dismutase (SOD) activity, and further using a single agent to evaluate the oxidative stress in CCl4-induced hepatotoxicity by immunofluorescence staining, maltol dramatically attenuated the reduction levels of hepatic CAT, GSH and SOD, and the over-expression levels of CYP2E1 and HO-1. In the mouse model of CCl4-induced liver injury, we have demonstrated that the inflammatory responses were inhibited, the serum levels of ALT and AST were reduced, cell apoptosis was suppressed, and liver injury caused by CCl4 was alleviated by maltol, demonstrating that maltol may be an efficient hepatoprotective agent.

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

“…Previous studies have shown that maltol inhibited hexanal oxidation in a dose-dependent manner, and neuroprotective effects of maltol against oxidative stress were also proposed by Kim and Wei et al [13,14]. Importantly, our previous study confirmed its potent antioxidant properties in TAA (thioacetamide) and alcohol-induced hepatic injury in vivo, which might be attributed to the prevention of lipid peroxidation and alleviation of the inflammation response [15,16,17].…”

Maltol prevents the progression of osteoarthritis by targeting PI3K/Akt/NF‐κB pathway: In vitro and in vivo studies

“…After DMM, the maltol treatment group received a dose of maltol for 100 mg·kg −1 ·day −1 (dissolved in saline, administered by oral gavage every day for 8 weeks) 44 . Simultaneously, mice in the DMM alone group received an equal amount of saline.…”

“…In these years, it is recognized that maltol prevents renal injuries by suppressing PI3K/AKT signalling pathway 19 . What's more, maltol has the protective property for oxidative stress such as glaucoma and attenuates liver apoptosis inflammation by inhibiting the NF‐κB signalling pathway 20 . Nevertheless, the protective effect of maltol in OA is still obscure.…”

The Effects of Environmental Factors on Ginsenoside Biosynthetic Enzyme Gene Expression and Saponin Abundance

“…Meyer is a perennial herb that grows slowly [1], and has a long history of medicinal use in traditional Chinese medicine. Ginseng has numerous pharmacological effects on humans, including acting against tumors, as an antioxidant, to inhibit fat accumulation [2,3,4], improving immunity, improving erectile function, and to help combat cardiovascular and cerebrovascular disease [5,6,7,8,9,10,11]. These benefits come with few adverse reactions or side effects.…”