Protective Effects of Sesamol against Liver Oxidative Stress and Inflammation in High-Fat Diet-Induced Hepatic Steatosis

Abstract

Chronic high-fat diet (HFD) is associated with the onset and progression of hepatic steatosis, and oxidative stress is highly involved in this process. The potential role of sesamol (SEM) against oxidative stress and inflammation at the transcriptional level in a mice model of hepatic steatosis is not known. In this study, we aimed to investigate the scavenging effects of SEM towards reactive oxygen generated by lipid accumulation in the liver of obese mice and to explore the mechanisms of protection. Markers of oxidative stress, vital enzymes involved in stimulating oxidative stress or inflammation, and nuclear transcription of Nrf2 were examined. Our results showed that SEM significantly inhibited the activity of the HFD-induced hepatic enzymes CYP2E1 and NOX2, associated with oxidative stress generation. Additionally, SEM reversed HFD-induced activation of NF-κB, a redox-sensitive transcription factor, and attenuated the expression of hepatic TNF-α, a proinflammatory molecule. Moreover, SEM enhanced HFD-induced hepatic Nrf2 nuclear transcription and increased the levels of its downstream target genes Ho1 and Nqo1, which indicated antiinflammation and antioxidant properties. Our study suggests that chronic HFD led to hepatic steatosis, while SEM exhibited protective effects on the liver by counteracting the oxidative stress and inflammation induced by HFD. The underlying mechanism might involve multiple pathways at the transcriptional level; the antioxidant defense mechanism was in partly mediated by the upregulation of Nrf2.

DHA-enriched phosphatidylcholine from Clupea harengus roes regulates the gut–liver axis to ameliorate high-fat diet-induced non-alcoholic fatty liver disease

“…45 SOD, GSH-Px, and CAT are important antioxidant enzymes that protect against lipid peroxidation. 44,45 In this study, DHA-PC effectively decreased MDA levels and increased SOD, GSH-Px, and CAT activities in the HFD murine liver tissues. Moreover, the increase in the body's inflammatory response may be closely related to long-term exposure to oxidative stress and LPS.…”

“…An imbalance between oxidants and antioxidant enzymes can cause oxidative stress, leading to the production of excessive reactive oxygen species (ROS). 44 The formation and accumulation of excess ROS are associated with NAFLD progression. 45 As an important indicator of the oxidation state, lipid peroxidase (MDA) is produced in large quantities by ROS attacking PUFAs in membrane phospholipids.…”

Polystyrene Microplastics Induce Oxidative Stress in Mouse Hepatocytes in Relation to Their Size

“…They form a barrier leading to the elimination of reactive oxygen species (ROS) and free radicals generated in the body under normal physiological conditions [ 3 , 4 ]. Oxidative stress is the result of an imbalance between oxidants and antioxidants [ 5 ]. Exposure to harmful stimuli leads to the overproduction of ROS, which may be in excess of the capacity of cellular antioxidant defense mechanisms to eliminate it.…”

“…It is now believed that oxidative stress is a common pathogenic mechanism contributing to several chronic liver diseases. The excessive production or accumulation of ROS in the liver can lead to diseases such as non-alcoholic fatty liver disease (NAFLD) and liver fibrosis [ 5 , 9 ]. Superoxide dismutase (SOD) is an important antioxidant enzyme.…”

Sesamol Mitigates Chronic Iron Overload‐Induced Cognitive Impairment and Systemic Inflammation via IL‐6 and DMT1 Regulation

“…It can effectively alleviate oxidative stress, reduce inflammation, and decrease lipid peroxide accumulation in the liver. [32,33] In the central nervous system, sesamol can cross the BBB and suppress LPS-induced neuroinflammation, cognitive deficits in APP/PS1 mice, and depressive-like behaviors induced by chronic unpredictable mild stress. [34][35][36][37] However, the ability of sesamol to prevent iron overload-induced cognitive decline has not yet been fully explored.…”