Morchella importuna Polysaccharides Alleviate Carbon Tetrachloride-Induced Hepatic Oxidative Injury in Mice.

Yingyin Xu,Jie Zhou,Liyuan Xie,Weihong Peng,Jie Tang,Zhiyuan Zhang,Xiaolan He,Ying Chen,Bingcheng Gan

doi:10.3389/fphys.2021.669331

Abstract

This study aimed to investigate the effects of Morchella importuna polysaccharides (MIPs) on carbon tetrachloride (CCl4)-induced hepatic damage in mice. A total of 144 female mice were randomly assigned to four treatment groups, namely, control, CCl4, low-dose MIP (LMIP) group, and high-dose MIP (HMIP) group. After the 10-day experiment, serum and liver were sampled for biochemical and metabolomic analyses. The HMIPs markedly decreased the liver weight under CCl4 intoxication. Furthermore, the significantly elevated concentrations of five serum biochemical parameters, including alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol, and total bile acid under CCl4 treatment were subverted by MIP administration in a dose-dependent manner. Moreover, MIPs relieved the increased hepatic malonaldehyde and protein carbonyl content and the decreased superoxide dismutase and catalase contents caused by CCl4 intoxication. There was also a dose-dependent decrease in the CCl4-induced inflammatory indices, such as the levels of interleukin-1, interleukin-6, tumor necrosis factor-alpha, and myeloperoxidase, with MIP administration. Subsequent ultra-high performance liquid chromatography–tandem mass spectrometry-based serum metabolomics identified nine metabolites between the control and CCl4 groups and 10 metabolites between the HMIP and CCl4 groups, including some critical metabolites involved in flavonoid biosynthesis, amino acid metabolism, energy metabolism, and toxicant degradation. These novel findings indicate that MIPs may be of therapeutic value in alleviating the oxidative stress and inflammation caused by CCl4. Liquid chromatography-mass spectrometry-based metabolomics provides a valuable opportunity for identifying potential biomarkers and elucidating the protective mechanisms of medicinal mushrooms against hepatic oxidative injury.

Highlights

The liver is considered a vital organ of the body with critical functions in protein synthesis, glucose homeostasis, detoxification, and nutrient utilization (Gao et al, 2008; AlSeeni et al, 2016)
The molecular weight (Mw) distribution of Morchella importuna polysaccharides (MIPs) was determined by highperformance gel chromatography (HP-GPC) using a Waters 515 high-performance liquid chromatograph equipped with a laser detector, a differential refractive index, and a Shodex OHpak SB806 gel chromatographic column (300 × 7.8 mm) set at 40◦C ± 0.1◦C
From the HP-GPC analysis, the Mw of MIPs was 35.54 kDa, the number-average molecular weight (Mn) was 34.77 kDa, and the D-value (Mw/Mn) was 1.002. These results indicated that the MIPs were relatively pure because the polydispersity ratio was close to 1, and the Mw distribution was narrow

Summary

Introduction

The liver is considered a vital organ of the body with critical functions in protein synthesis, glucose homeostasis, detoxification, and nutrient utilization (Gao et al, 2008; AlSeeni et al, 2016). The high levels of environmental toxins, alcohol, heavy metals, and metabolic dysfunction of the liver are among various insults that may lead to acute or chronic hepatic injury, followed by progressive fibrosis, cirrhosis, and even carcinoma (Sun et al, 2011; Nwokocha et al, 2012; Su et al, 2019; Chan et al, 2020). Due to the implication of oxidative stress and inflammation in the etiology of liver injury, carbon tetrachloride (CCl4), a typical environmental toxicant, is widely used in experimental hepatopathy (Zou et al, 2016). Trichloromethyl peroxyl (Cl3COO) radicals subsequently bind to proteins or lipids initiating lipid peroxidation and culminate in liver injury due to depletion of antioxidant enzymes (McGill and Jaeschke, 2013; Dong et al, 2015).

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