RGD Reference Report - Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats. - Rat Genome Database

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Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats.

Authors: Mahmoud, Ayman M  Hussein, Omnia E  Hozayen, Walaa G  Bin-Jumah, May  Abd El-Twab, Sanaa M 
Citation: Mahmoud AM, etal., Environ Sci Pollut Res Int. 2020 Mar;27(8):7910-7921. doi: 10.1007/s11356-019-07532-6. Epub 2019 Dec 31.
RGD ID: 21201308
Pubmed: PMID:31889292   (View Abstract at PubMed)
DOI: DOI:10.1007/s11356-019-07532-6   (Journal Full-text)

Liver injury is one of the adverse effects of methotrexate (MTX). Ferulic acid (FA) is an antioxidant phytochemical that confers hepatoprotective efficacy; however, its effect against MTX hepatotoxicity remains unexplored. This study investigated the role of FA in modulating oxidative stress, inflammation, Nrf2/HO-1 signaling, and PPARγ in MTX-administered rats. Following oral FA supplementation for 15 days, rats received a single dose of MTX at day 16 and samples were collected at day 19. MTX provoked multiple histological manifestations, including degenerative changes, steatosis, inflammatory cells infiltration and hemorrhage, and altered serum transaminases, bilirubin, and albumin. Reactive oxygen species, lipid peroxidation, and nitric oxide were increased in the liver of rats that received MTX. FA prevented all histological alterations, ameliorated liver function markers, suppressed oxidative stress, and boosted antioxidants in MTX-induced rats. FA reduced serum TNF-α and IL-1β, and hepatic NF-κB p65, Bax, and caspase-3, whereas increased Bcl-2, Nrf2, NQO1, HO-1, and PPARγ. In conclusion, FA prevented MTX hepatotoxicity by activating Nrf2/HO-1 signaling and PPARγ, and attenuating oxidative stress, inflammation, and cell death.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NFE2L2HumanChemical and Drug Induced Liver Injury treatmentISONfe2l2 (Rattus norvegicus)induced by methotrexate (CHEBI:44185), treated by ferulic acid (CHEBI:17620)RGD 
Nfe2l2RatChemical and Drug Induced Liver Injury treatmentIEP induced by methotrexate (CHEBI:44185), treated by ferulic acid (CHEBI:17620)RGD 
Nfe2l2MouseChemical and Drug Induced Liver Injury treatmentISONfe2l2 (Rattus norvegicus)induced by methotrexate (CHEBI:44185), treated by ferulic acid (CHEBI:17620)RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NQO1Humanmethotrexate decreases expression ISONqo1 (Rattus norvegicus)Methotrexate decreases Nqo1 mRNA in the liverRGD 
Nqo1Ratmethotrexate decreases expression IEP Methotrexate decreases Nqo1 mRNA in the liverRGD 
Nqo1Mousemethotrexate decreases expression ISONqo1 (Rattus norvegicus)Methotrexate decreases Nqo1 mRNA in the liverRGD 
NQO1Humantrans-ferulic acid multiple interactionsISONqo1 (Rattus norvegicus)Ferulic acid reverses the reaction[methotrexate decreases mRNA in the liver]RGD 
Nqo1Rattrans-ferulic acid multiple interactionsIEP Ferulic acid reverses the reaction[methotrexate decreases mRNA in the liver]RGD 
Nqo1Mousetrans-ferulic acid multiple interactionsISONqo1 (Rattus norvegicus)Ferulic acid reverses the reaction[methotrexate decreases mRNA in the liver]RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nqo1Ratresponse to organic cyclic compound  IEP Ferulic acid RGD 
Nqo1Ratresponse to xenobiotic stimulus  IEP Methotrexate RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Objects Annotated

Genes (Rattus norvegicus)
Nfe2l2  (NFE2 like bZIP transcription factor 2)
Nqo1  (NAD(P)H quinone dehydrogenase 1)

Genes (Mus musculus)
Nfe2l2  (nuclear factor, erythroid derived 2, like 2)
Nqo1  (NAD(P)H dehydrogenase, quinone 1)

Genes (Homo sapiens)
NFE2L2  (NFE2 like bZIP transcription factor 2)
NQO1  (NAD(P)H quinone dehydrogenase 1)


Additional Information