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Protective effects of dioscin against alcohol-induced liver injury

  • Organ Toxicity and Mechanisms
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A Correction to this article was published on 29 August 2019

This article has been updated

Abstract

Our previous studies have shown that dioscin has protective effect against liver injury. However, the action of the compound against ethanol-induced liver injury is still unknown. In the present paper, ethanol-induced acute and chronic liver damage rat models were used, and the results showed that dioscin significantly alleviated liver steatosis, reduced the levels of alanine aminotransferase, aspartate aminotransferase, total triglyceride (TG), total cholesterol and malondialdehyde, and increased the levels of high-density lipoprotein, superoxide dismutase, glutathione and glutathione peroxidase. Transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays showed that dioscin prevented mitochondrial ultrastructural alterations and apoptosis caused by ethanol. In addition, dioscin significantly inhibited ethanol-induced cytochrome P450 2E1 activation, down-regulated the levels of mitogen-activated protein kinases phosphorylation, inhibited the expressions of nuclear factor kappa B, glucose regulated protein 78, activating transcription factor 6 and alpha subunit of translation initiation factor 2 to attenuate oxidative damage, decreased the expressions of tumor necrosis factor alpha and interleukin-6, and down-regulated the expressions of apoptosis-related proteins including p53, caspase-3, caspase-9, poly (ADP-ribose)-polymerase and cytokeratin-18. Further investigation indicated that dioscin markedly increased the expressions of peroxisome proliferators-activated receptor α and its target genes including medium-chain acyl-CoA dehydrogenase, carnitine palmitoyl-CoA transferase I and acyl-CoA oxidase to advance fatty acid β-oxidation, up-regulated the expressions of acyl-CoA synthetase long-chain family member 1, acyl-CoA synthetase long-chain family member 5, alpha-aminoadipic semialdehyde dehydrogenase and acyl-CoA dehydrogenase to promote fatty acid metabolism, and down-regulated the expressions of glycerol-3-phosphate acyltransferase, diacylglycerol acyltransferase 1 and diacylglycerol acyltransferase 2 to accelerate TG synthesis. However, dioscin had no effects on the expressions of sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase 1 associated with fatty acid synthesis. In conclusion, dioscin shows excellent protective effect against ethanol-induced liver injury through ameliorating ethanol-induced oxidative stress, mitochondrial function, inflammatory cytokine production, apoptosis and liver steatosis, which should be developed as a new drug for the treatment of ethanol-induced liver injury in the future.

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Change history

  • 29 August 2019

    During the course of writing and revision of this paper, the band of GAPDH.

  • 29 August 2019

    During the course of writing and revision of this paper, the band of GAPDH.

Abbreviations

APAP:

Acetaminophen

CCl4 :

Carbon tetrachloride

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

TC:

Total cholesterol

TG:

Total triglyceride

MDA:

Malondialdehyde

HDL:

High-density lipoprotein

SOD:

Superoxide dismutase

GSH:

Glutathione

GSH-Px:

Glutathione peroxidase

GSR:

Glutathione reductase

Ct:

Threshold cycle

CYP2E1:

Cytochrome P450 2E1

ROS:

Reactive oxygen species

MAPKs:

Mitogen-activated protein kinases

NF-κB:

Nuclear factor kappa B

GRP78:

Glucose regulated protein 78

ATF6:

Activating transcription factor 6

EIF2:

Alpha subunit of translation initiation factor 2

TNF-α:

Tumor necrosis factor alpha

IL-6:

Interleukin-6

PARP:

Poly (ADP-ribose)-polymerase

TEM:

Transmission electron microscopy

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling

PPAR-α:

Peroxisome proliferators-activated receptor α

MCAD:

Medium-chain acyl-CoA dehydrogenase

CPT I:

Carnitine palmitoyl-CoA transferase I

ACO:

Acyl-CoA oxidase

ACSL1:

Acyl-CoA synthetase long-chain family member 1

ACSL5:

Acyl-CoA synthetase long-chain family member 5

ALDH7A1:

Alpha-aminoadipic semialdehyde dehydrogenase

ACADS:

Acyl-CoA dehydrogenase

GAPT:

Glycerol-3-phosphate acyltransferase

DAGT1:

Diacylglycerol acyltransferase 1

DAGT2:

Diacylglycerol acyltransferase 2

SREBP-1c:

Sterol regulatory element-binding protein-1c

FAS:

Fatty acid synthase

ACC1:

Acetyl-CoA carboxylase 1

SCD1:

Stearoyl-CoA desaturase 1

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Acknowledgments

This work was financially supported by National Natural Science Foundation of China (No. 81274195) and the Program for New Century Excellent Talents in University (NCET-11-1007).

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Correspondence to Jinyong Peng.

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Xu, T., Zheng, L., Xu, L. et al. Protective effects of dioscin against alcohol-induced liver injury. Arch Toxicol 88, 739–753 (2014). https://doi.org/10.1007/s00204-013-1148-8

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