Cadmium Induces Acute Liver Injury by Inhibiting Nrf2 and the Role of NF-κB, NLRP3, and MAPKs Signaling Pathway.
Animals
Cadmium
/ toxicity
Chemical and Drug Induced Liver Injury
/ genetics
MAP Kinase Signaling System
/ drug effects
Male
Mice
Mitogen-Activated Protein Kinases
/ drug effects
Models, Animal
NF-E2-Related Factor 2
/ drug effects
NF-kappa B
/ drug effects
NLR Family, Pyrin Domain-Containing 3 Protein
/ drug effects
Cadmium
MAPKs
NF-κB
NLRP3
Nrf2
acute liver injury
Journal
International journal of environmental research and public health
ISSN: 1660-4601
Titre abrégé: Int J Environ Res Public Health
Pays: Switzerland
ID NLM: 101238455
Informations de publication
Date de publication:
24 12 2019
24 12 2019
Historique:
received:
14
11
2019
revised:
11
12
2019
accepted:
20
12
2019
entrez:
28
12
2019
pubmed:
28
12
2019
medline:
17
4
2020
Statut:
epublish
Résumé
Acute Cadmium (Cd) exposure usually induces hepatotoxicity. It is well known that oxidative stress and inflammation causes Cd-induced liver injury. However, the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) in Cd-induced liver injury is not completely understood. In this study, we observed Cd-induced liver damage and the potential contribution of Nrf2, nuclear factor-κB (NF-κB), Nod-like receptor 3 (NLRP3), and mitogen-activated protein kinases (MAPKs) signaling pathways. Changes in serum transaminases and proinflammatory cytokines expression showed that Cd could induce acute hepatotoxicity. Moreover, Nrf2 and its downstream heme oxygenase 1 (HO-1) were inhibited by Cd exposure, and Kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2, was increased. Furthermore, NF-κB, NLRP3, and MAPKs signaling pathways were all activated by Cd intoxication. In conclusion, the inhibition of Nrf2, HO-1, and the activation of NF-κB, NLRP3, and MAPKs all contribute to Cd-induced liver injury.
Identifiants
pubmed: 31878134
pii: ijerph17010138
doi: 10.3390/ijerph17010138
pmc: PMC6981660
pii:
doi:
Substances chimiques
NF-E2-Related Factor 2
0
NF-kappa B
0
NLR Family, Pyrin Domain-Containing 3 Protein
0
NLRP3 protein, human
0
Cadmium
00BH33GNGH
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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