Activated carbon N-acetylcysteine microcapsule protects against nonalcoholic fatty liver disease in young rats via activating telomerase and inhibiting apoptosis.

Tingting Shi,Xingxin Yang,Jiankang Zhang,Jingjing Sun,Yunling Ke,Jianjun Xi,Yidan Shao,Hongping Zhou,Shourong Liu,Xiaojie Jiang,Rangxiao Zhuang,Xuwang Pan,Jordi Gracia-Sancho

doi:10.1371/journal.pone.0189856

Abstract

Non-alcoholic fatty liver disease (NAFLD) is becoming one of the world's most common chronic liver diseases in childhood, yet no therapy is available that has been approved by the food and drug administration (FDA). Previous studies have reported that telomere and telomerase are involved the development and progression of NAFLD. This study was designed to investigate the potential beneficial effects of activated carbon N-acetylcysteine (ACNAC) microcapsules on the development of NAFLD in young rats as well as the underlying mechanism(s) involved. Three-week old male Sprague Dawley rats were given high-fat diet (HFD) with/without ACNAC treatment for 7 consecutive weeks. Liver pathologies were determined by hematoxylin and eosin (H&E) and Oil Red O staining, as well as by changes in biochemical parameters of plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, respectively. Glucose homeostasis was evaluated by the glucose tolerance test and the liver telomere length and activity were measured by real time PCR and telomeric repeat amplification protocol (TRAP). Western blot analysis was performed to determine the expression level of Bcl-2, Bax and Caspase-3. Our results demonstrated that ACNAC supplementation improved liver pathologies of rats that received long-term HFD feeding. ACNAC supplementation prevented HFD-induced telomere shortening and improved telomerase activity. Moreover, in comparison to HFD-fed rats, ACNAC supplementation markedly increased the expression of Bcl-2, but significantly decreased the expression of Bax and Caspase-3 in juvenile rats. Together, these results indicate that ACNAC may be a promising choice for preventing and treating NAFLD among children.

Highlights

In coastal areas of China, non-alcoholic fatty liver disease (NAFLD) has become one of the most common diseases among higher modern living standards, better dietary structure, accelerated aging and advanced medical and health undertakings[1,2]
Professional pathologists classified the hepatic steatosis and inflammation in the hepatic lobules according to the results of hematoxylin and eosin (H&E) and ORO staining in liver tissues
H&E staining results: The normal group showed integral hepatic lobule structure, radial arrangement of liver cells around the center of central vein, clear boundaries of liver cells, nucleus in the central cell and clear outline of hepatic lobules (Fig 1A), while in the model group, the liver cell volume was significantly increased, mild and moderate to severe steatosis and ballooning were observed in liver tissues, vacuoles of different sizes were filled in the cells, and some inflammatory cells and focal necrosis were observed in some areas(Fig 1B)

Summary

Introduction

In coastal areas of China, non-alcoholic fatty liver disease (NAFLD) has become one of the most common diseases among higher modern living standards, better dietary structure, accelerated aging and advanced medical and health undertakings[1,2]. Epidemiological data indicated that in foreign adults, the incidence of NAFLD is 20% to 33% [3], whereas in healthy children around the world the incidence is 3% to 10% [4]. NAFLD involves a series of liver pathological changes in children ranging from simple fatty liver degeneration to non-alcoholic steatohepatitis (NASH), liver fibrosis and liver cirrhosis [6,7,8]. NAFLD has become one of the world’s most common chronic liver diseases in childhood, which is evidenced by its incidence [9], and has gained increased attention

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Conclusion