Abstract

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease caused by oxidative stress, inflammation and lipid deposition within liver cells, and is subsequently contributing to cardiovascular diseases such as atherosclerosis. Deep sea water (DSW) is characterized by its clearance and abundant nutrients with antioxidant and anti-inflammatory activity to confer therapeutic potential. We aimed to explore the therapeutic capability of our prepared multi-filtration DSW-dissolved organic matter (DSW-DOM) on high-fat diet-induced hyperlipidemia and endothelial dysfunction in hamsters. A high-fat/high-cholesterol diet led to increased oxidative stress, including blood reactive oxygen species (ROS), plasma malondialdehyde (MDA) and hepatic CYP2E1 expression; an increased hyperlipidemic profile and SREBP 1-mediated fatty liver; promoted NFκB p65-mediated hepatic inflammation; triggered PARP-mediated hepatic apoptosis; and enhanced endothelial intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (VWF)-mediated atherosclerosis associated with the depressed hepatic antioxidant Paraoxonase 1 (PON1) expression. The DSW-DOM-enriched 1295 fraction, with strong H2O2 scavenging activity, efficiently reduced several oxidative stress parameters, the lipid profile, inflammation, and apoptosis, possibly through the PON1-mediated antioxidant capability. Furthermore, DSW-DOM treatment significantly decreased the endothelial ICAM-1 and VWF expression, subsequently leading to the elongation of time to occlusion of FeCl3-induced arterial thrombosis and to the inhibition of FeCl3-induced fluorescent platelet adhesion to mesentery arterioles in the high-fat diet. Based on the above results, our data suggest that DSW-DOM intake via antioxidant defense mechanisms confers protective effects against high-fat diet-enhanced, oxidative stress-mediated hyperlipidemia, and endothelial dysfunction evoked atherosclerosis by downregulating oxidative injury, lipogenesis, inflammation and apoptosis.

Highlights

  • Hyperlipidemia is a well-known risk factor for cardiovascular diseases (CVDs) and can be classified as either familial or acquired

  • Acquired hyperlipidemia comes from unbalanced eating habit or metabolic disorders that lead to alterations in plasma lipid and lipoprotein metabolism [1]

  • HCD-HD showed increased Paraoxonase 1 (PON1) expression in Western blot. These results proved that the reduced total cholesterol came from an increasing quality and quantity of high-density cholesterol (HDL) by Deep sea water (DSW)-dissolved organic matter (DOM)

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Summary

Introduction

Hyperlipidemia is a well-known risk factor for cardiovascular diseases (CVDs) and can be classified as either familial or acquired. High blood cholesterol and triglyceride (TG) levels are commonly considered as leading biomarkers of hyperlipidemic processes [2]. Increased blood cholesterol, such as low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and total cholesterol (TC), leads to a high risk of hypertension, atherosclerosis and other CVDs [3,4,5]. Blood cholesterol levels are highly associated with hepatic lipid metabolism since cholesterol is synthesized in the liver. Hepatic lipid metabolism is an important target to evaluate the pharmacological effect on hyperlipidemia [6]

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