Elsevier

Free Radical Biology and Medicine

Volume 143, 1 November 2019, Pages 47-54
Free Radical Biology and Medicine

Original article
Determination of the effects of torularhodin against alcoholic liver diseases by transcriptome analysis

https://doi.org/10.1016/j.freeradbiomed.2019.07.033Get rights and content

Highlights

  • Initial use of torularhodin in the treatment of alcoholic liver injury in mice.

  • To study the effects of torularhodin on oxidative damage and abnormal lipid metabolism induced by alcoholic liver injury in mice.

  • The effects of torularhodin on the mechanism and pathway of alcoholic liver injury in mice were studied by transcriptome analysis.

Abstract

Alcoholic liver disease (ALD) is a major cause of liver injury worldwide. Oxidative damage is one of the main injuries caused by ALD. The aim of this study was to elucidate the preventive effects of torularhodin, extracted from Sporidiobolus pararoseus, on alcoholic liver injury in mice. The mechanisms involved were investigated using transcriptome analysis. Torularhodin supplementation decreased ethanol-induced aspartate transaminase (ALT), aspartate transaminase (AST) and low density lipoprotein (LDL) levels, and increased high density lipoprotein (HDL) levels in the serum of mice. In liver tissue, treatment with torularhodin increased ethanol-induced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels and decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels. Histological analysis showed that torularhodin could alleviate the negative effects of alcohol on the liver. Transcriptomic analysis showed that 806 genes were significantly differentially expressed (506 up-regulated and 300 down-regulated) after torularhodin treatment. These genes were involved in three main Gene Ontology categories (biological process, cellular component, and molecular function) and multiple pathways. Therefore, torularhodin was considered to have potential as a protective agent against ALD.

Introduction

The liver is a vital organ and plays an irreplaceable role in metabolic function in the human body. It has multifarious, irreplaceable functions, including conversion of nutrients to critical blood components, storage of vitamins and minerals, manufacture of various plasma proteins, maintenance of hormonal metabolism, and processing of toxic wastes of the body [1]. In modern times, the liver is increasingly threatened by bad lifestyle habits and environmental factors, such as pollutants, fried food and drug and alcohol misuse. Alcoholic liver disease (ALD) is a major cause of liver-related morbidity and mortality all over the world and includes various liver-related diseases, ranging from simple steatosis to severe forms of liver injury, such as steatohepatitis, cirrhosis and hepatocellular carcinoma [[2], [3], [4], [5], [6]]. Alcohol can increase metabolic pressure and cause oxidative damage to the liver. Most alcoholics have fatty liver and may worsen to more severe liver disease. The oxidative damage caused by excessive alcohol intake is a major cause of liver injury. Therefore, alcohol-induced liver injuries are considered a serious health problem, attracting worldwide attention.

Carotenoid is an organic substance found in vegetables, fruits, eggs, oil and fish [7,8]. It plays a crucial role in maintaining human health. Carotenoids are the main source of dietary vitamin A, and also have antioxidant, immunomodulatory, anti-cancer and anti-aging effects. Carotenoids can also prevent oxidative damage in organs owing to their anti-oxidative properties [9,10]. Torularhodin is one of the most abundant carotenoids in the fungus Sporidiobolus pararoseus and has a non-cyclic β-ionone ring. Its structure is similar to lycopene, except for one additional double bond [[11], [12], [13]]. Therefore, it is considered to have stronger antioxidant capacity than lycopene. Some studies have suggested that torularhodin has anti-oxidative, anti-cancer and anti-microbial properties [[14], [15], [16], [17]]. Therefore, torularhodin has good potential to protect the liver from oxidative damage.

The potential antioxidant effects of torularhodin against alcohol-induced oxidative damage of the liver have not been thoroughly studied. The objective of the present study was to elucidate the potential antioxidant activities and the molecular mechanisms of torularhodin during alcoholic liver oxidation injury in mice. Additionally, we sought to identify, confirm, analyze and compare differentially expressed genes (DEGs) in torularhodin-treated and control mice.

Section snippets

Materials

Sporidiobolus pararoseu JD-2 was obtained from the School of Biotechnology Jiangnan University. Torularhodin was isolated and purified from the extract of S. pararoseus according to a previously published method [18]. Oily crude extract from yeast was extracted using acid heat method. Fermentation broth was centrifuged at 8000 r/min for 30 min. The precipitate was heated with the same volume of hydrochloric acid (HCL) (2 mol/l) for 15 min. After acid treatment, the extract was rapidly cooled

Effects of torularhodin on serum biochemical parameters

As shown in Fig. 1, ALT, AST and LDL levels in the Damage group mice were higher, whereas HDL levels were lower, than those in Control group mice, indicating that the model was successfully established (p < 0.05). Compared with the levels in the Damage group, ALT, AST and LDL levels in the Tor groups were evidently decreased, whereas the HDL level was increased, suggesting that treatment with torularhodin had a positive effect on alcohol-induced liver injury.

Torularhodin has antioxidant and anti-inflammatory effects in liver tissue

As shown in Fig. 2, compared with

Discussion

Alcohol-induced liver injury is a common characteristic in the pathogenesis of alcoholic liver disease. Continuous alcohol intake can aggravate alcoholic liver disease, leading to liver steatosis, alcoholic hepatitis, cirrhosis, and ultimately liver cancer [21]. Therefore, inhibition of alcoholic liver injury can reduce the incidence and progression of alcoholic liver disease. The model of alcoholic liver injury selected for this study could better demonstrate the damage caused by

Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of interest

The authors have no conflicts of interest in relation to this study to report.

Acknowledgments

The work reported in this article is supported by the National Key Research and Development Program of China (Project No.2017YFC1601806), National Key Research and Development Program of China (Project No. 2017YFC1601704), Natural Science Foundation of Jiangsu Province (No.BK20160178), National Natural Science Foundation of China (No.21603087), National First-class Discipline Program of Food Science and Technology (JUFSTR20180303), Science and Technology Support Plan of Jiangsu Province (

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