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Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2-Keap1 Signaling Pathway
- Source :
- Oxidative Medicine and Cellular Longevity, Vol 2018 (2018), Oxidative Medicine and Cellular Longevity
- Publication Year :
- 2018
- Publisher :
- Hindawi Limited, 2018.
-
Abstract
- The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real-time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2−Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP-mediated Nrf2 activation triggered the transcription and expressions of the glutamate–cysteine ligase catalytic (GCLC) subunit, glutamate–cysteine ligase regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP-induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2−Keap1 signaling pathway.
- Subjects :
- 0301 basic medicine
Male
Aging
Article Subject
NF-E2-Related Factor 2
Pharmacology
medicine.disease_cause
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Polysaccharides
medicine
Animals
lcsh:QH573-671
Acetaminophen
Liver injury
chemistry.chemical_classification
Reactive oxygen species
Kelch-Like ECH-Associated Protein 1
biology
Chemistry
GCLM
lcsh:Cytology
Cell Biology
General Medicine
Glutathione
medicine.disease
Malondialdehyde
030104 developmental biology
GCLC
030220 oncology & carcinogenesis
Myeloperoxidase
biology.protein
Chemical and Drug Induced Liver Injury
Oxidative stress
Research Article
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19420994 and 19420900
- Volume :
- 2018
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....89557183b5d23d8cf416de6ff46c890a