Boldine treatment protects acetaminophen-induced liver inflammation and acute hepatic necrosis in mice.
acetaminophen
boldine
glutathione
hepatic necrosis
Journal
Journal of biochemical and molecular toxicology
ISSN: 1099-0461
Titre abrégé: J Biochem Mol Toxicol
Pays: United States
ID NLM: 9717231
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
revised:
21
10
2020
received:
10
06
2020
accepted:
12
12
2020
pubmed:
5
1
2021
medline:
28
7
2021
entrez:
4
1
2021
Statut:
ppublish
Résumé
Drug-induced liver injury (DILI) is a frequent cause responsible for acute liver failure (ALF). Acetaminophen (APAP) is a known hepatotoxin predictably causing intrinsic DILI. At high doses, APAP causes acute liver necrosis and responsible for ALF and liver transplant cases in 50% and 20% of patients, respectively, in the United States alone. Oxidative stress and glutathione depletion are implicated in APAP-induced liver necrosis. Boldine, a plant-derived compound is shown to have promising antioxidant potential. Therefore, this study investigates the protective effect of boldine against APAP-induced acute hepatic necrosis in mice. A single toxic dose of APAP (300 mg/kg b.w. p.o.) was administered in overnight-fasted mice to induce acute liver necrosis. Separately, APAP + boldine and APAP + N-acetylcysteine (NAC) simultaneous treatments were also given. Serum transaminases and reduced glutathione, enzymic antioxidants, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and, IL-6 were evaluated in liver tissue. Acute APAP intoxication significantly elevated serum marker enzymes of hepatotoxicity. APAP administration increased lipid peroxidation, TNF-α, IL-1β, and IL-6 protein expressions. The enzymic antioxidants and reduced glutathione levels were decreased in liver tissue of APAP intoxicated mice. Boldine and NAC simultaneous treatments prevented APAP-induced oxidative stress, inflammation, and necrosis. The results of this study suggest the crucial role of boldine to protect against APAP induced hepatotoxicity by virtue of its antioxidant and anti-inflammatory properties.
Substances chimiques
Aporphines
0
Cytokines
0
Acetaminophen
362O9ITL9D
boldine
8I91GE2769
Acetylcysteine
WYQ7N0BPYC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22697Informations de copyright
© 2021 Wiley Periodicals LLC.
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