Kaempferol suppresses acetaminophen-induced liver damage by upregulation/activation of SIRT1

Autor: Nora Abdullah AlFaris, Mona Nasser BinMowyna
Rok vydání: 2021
Předmět:
Male
Antioxidant
medicine.medical_treatment
Flavonoid
Anti-Inflammatory Agents
Pharmaceutical Science
Pharmacology
medicine.disease_cause
030226 pharmacology & pharmacy
01 natural sciences
Antioxidants
chemistry.chemical_compound
0302 clinical medicine
Sirtuin 1
Drug Discovery
apap
oxidative stress
chemistry.chemical_classification
digestive
oral
and skin physiology
apoptosis
food and beverages
General Medicine
Up-Regulation
Molecular Medicine
Chemical and Drug Induced Liver Injury
hepatic
medicine.drug
macromolecular substances
03 medical and health sciences
Downregulation and upregulation
medicine
Animals
Kaempferols
Rats
Wistar
Acetaminophen
Superoxide Dismutase
lcsh:RM1-950
Glycoside
Rats
0104 chemical sciences
010404 medicinal & biomolecular chemistry
lcsh:Therapeutics. Pharmacology
Complementary and alternative medicine
chemistry
Apoptosis
flavonoids
Reactive Oxygen Species
Kaempferol
Oxidative stress
Zdroj: Pharmaceutical Biology, Vol 59, Iss 1, Pp 146-156 (2021)
ISSN: 1744-5116
1388-0209
Popis: Context Kaempferol, a flavonoid glycoside, has many hepatoprotective effects in several animals due to its antioxidant potential. Objective This study evaluated the hepatoprotective effect of kaempferol against acetaminophen (APAP)-induced liver damage and examined whether the protection involved modulation of silent information regulator 1 (SIRT1) signalling. Materials and methods Adult male Wistar rats were classified into four groups (n = 8) and treated as follows: control + normal saline (vehicle), control + kaempferol (250 mg/kg), APAP (800 mg/kg, a single dose) and APAP + kaempferol. Kaempferol was administered for the first seven days followed by administration of APAP. The study was ended 24 h after APAP administration. Results At the histological level, kaempferol reduced liver damage in APAP-treated rats. It also reduced the hepatic levels of TNF-α (66.3%), IL-6 (38.6%) and protein levels of caspase-3 (88.2%), and attenuated the increase in circulatory serum levels of ALT (47.6%), AST (55.8%) and γ-GT (35.2%) in APAP-treated rats. In both the controls and APAP-treated rats, kaempferol significantly increased the hepatic levels of glutathione (GSH) and superoxide dismutase, suppressed MDA and reactive oxygen species (ROS) levels, increased protein levels of Bcl-2 and downregulated protein levels of Bax and cleaved Bax. Concomitantly, it reduced the expression of CYP2E1, and the activity and protein levels of SIRT1. Consequently, it decreased the acetylation of all SIRT1 targets including PARP1, p53, NF-κB, FOXO-1 and p53 that mediate antioxidant, anti-inflammatory and anti-apoptotic effects. Discussion and conclusions This study encourages the use of kaempferol in further clinical trials to treat APAP-induced hepatotoxicity.
Databáze: OpenAIRE
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