Auriculatone Sulfate Effectively Protects Mice Against Acetaminophen-Induced Liver Injury

Autor: Liang-cai Lin, Yongjun Li, Xun He, Guan Huanyu, Wang Yonglin, Liao Xiangming, Li Rui, Zhao Feifei, Shang-Gao Liao, Guo-Bo Xu, Jing Li, Meng Zhou, Jin-Juan Zhang, Min Wang
Rok vydání: 2019
Předmět:
Pharmaceutical Science
Pharmacology
auriculatone sulfate
medicine.disease_cause
030226 pharmacology & pharmacy
Analytical Chemistry
chemistry.chemical_compound
Mice
0302 clinical medicine
Aacetaminophen-induced hepatotoxicity
Drug Discovery
Liver injury
chemistry.chemical_classification
0303 health sciences
biology
Molecular Structure
Chemistry
Glutathione peroxidase
digestive
oral
and skin physiology
hepatoprotective effect
CYP2E1
Analgesics
Non-Narcotic
Mitochondria
Liver
Chemistry (miscellaneous)
Molecular Medicine
Cytokines
Chemical and Drug Induced Liver Injury
Inflammation Mediators
medicine.drug
CYPs inhibition
Protective Agents
Article
Superoxide dismutase
lcsh:QD241-441
03 medical and health sciences
lcsh:Organic chemistry
medicine
Animals
Physical and Theoretical Chemistry
Hepatoprotective Agent
030304 developmental biology
Acetaminophen
Organic Chemistry
Glutathione
medicine.disease
Oxidative Stress
inflammation
biology.protein
Reactive Oxygen Species
Oxidative stress
Zdroj: Molecules
Volume 24
Issue 20
Molecules, Vol 24, Iss 20, p 3642 (2019)
ISSN: 1420-3049
Popis: Acetaminophen (APAP) overdose is very common worldwide and has been widely recognized as the leading cause of drug-induced liver injury in the Western world. In our previous investigation, auriculatone, a natural product firstly obtained from Aster auriculatus, has demonstrated a potent protective effect against APAP-induced hepatotoxicity in HL-7702 cells. However, the poor water solubility and low bioavailability restrict its application. Auriculatone sulfate (AS) is a sulfated derivative of auriculatone with highly improved water-solubility. Hepatoprotective effects against APAP-induced liver injury (AILI) showed that intragastric pretreatment with AS at 50 mg/kg almost completely prevented mice against APAP-induced increases of serum alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and ATPase. Histological results showed that AS could protect the liver tissue damage. In addition, AS pretreatment not only significantly retained hepatic malondialdehyde and the activities of glutathione, superoxide dismutase, and glutathione peroxidase at normal levels, but also markedly suppressed the increase of pro-inflammatory cytokines TNF-&alpha
IL-1&beta
and IL-6 levels in mouse liver caused by overdose APAP. Immunohistochemical analysis showed that AS obviously attenuated the expression of CD45 and HNE in liver tissue. Further mechanisms of action investigation showed that inhibition of cytochrome P450 3A11 (CYP 3A11) and CYP2E1 enzymatic activities (but not that of CYP1A2) was responsible for APAP bioactivation. In conclusion, AS showed a hepatoprotective effect against AILI through alleviating oxidative stress and inflammation and inhibiting CYP-mediated APAP bioactivation. It may be an effective hepatoprotective agent for AILI and other forms of human liver disease.
Databáze: OpenAIRE
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