Kaempferol Inhibits Zearalenone-Induced Oxidative Stress and Apoptosis via the PI3K/Akt-Mediated Nrf2 Signaling Pathway: In Vitro and In Vivo Studies
Authors: Rebai Ben Ammar
Gamal M Bekhet
Fatma J Al-Saeedi
Ahmed M Soliman
Medhat A ElNaggar
Peramaiyan Rajendran
Saeed Y Al-Ramadan
Maged E Mohamed
Journal: International Journal of Molecular Sciences (2020)
Discipline: CHEMISTRY
Keywords: Nrf2; PI3K/Akt; apoptosis; hepatotoxicity; kaempferol
Affiliations: Department of Biological Sciences, College of Science, King Faisal University, Al-Ahsa 31982, Saudi Arabia., Laboratory of Aromatic and Medicinal Plants, Center of Biotechnology, Technopole of Borj-Cedria, Hammam-Lif 901 2050, Tunisia., Department of Nuclear Medicine, Faculty of Medicine, Kuwait University, Safat 13110, Kuwait., Pharmaceutical Sciences Department, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia., Pharmacognosy Department, College of Pharmacy, Zagazig University, Zagazig 44519, Egypt., Plant Pathology Research Institute, Agricultural Research Center, Giza Governorate 12619, Egypt., Research Central Laboratory, Saudi Grains Organization, Riyadh 11471, Saudi Arabia., Department of Anatomy, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia., Department of Zoology, Faculty of Science, Alexandria University Egypt, Alexandria 21544, Egypt., Department of Arid Land Agriculture, College of Agricultural & Food Sciences, King Faisal University, Al Ahsa 31982, Saudi Arabia., Virus & Phytoplasma Research Department, Plant Pathology Research Institute, Agricultural Research Center, Giza Governorate 1266, Egypt.

Abstract:  In this study, kaempferol (KFL) shows hepatoprotective activity against zearalenone (ZEA)-induced oxidative stress and its underlying mechanisms in in vitro and in vivo models were investigated. Oxidative stress plays a critical role in the pathophysiology of various hepatic ailments and is normally regulated by reactive oxygen species (ROS). ZEA is a mycotoxin known to exert toxicity via inflammation and ROS accumulation. This study aims to explore the protective role of KFL against ZEA-triggered hepatic injury via the PI3K/Akt-regulated Nrf2 pathway. KFL augmented the phosphorylation of PI3K and Akt, which may stimulate antioxidative and antiapoptotic signaling in hepatic cells. KFL upregulated Nrf2 phosphorylation and the expression of antioxidant genes HO-1 and NQO-1 in a dose-dependent manner under ZEA-induced oxidative stress. Nrf2 knockdown via small-interfering RNA (siRNA) inhibited the KFL-mediated defence against ZEA-induced hepatotoxicity. In vivo studies showed that KFL decreased inflammation and lipid peroxidation and increased H2O2 scavenging and biochemical marker enzyme expression. KFL was able to normalize the expression of liver antioxidant enzymes SOD, CAT and GSH and showed a protective effect against ZEA-induced pathophysiology in the livers of mice. These outcomes demonstrate that KFL possesses notable hepatoprotective roles against ZEA-induced damage in vivo and in vitro. These protective properties of KFL may occur through the stimulation of Nrf2/HO-1 cascades and PI3K/Akt signaling. 

Retracted: No

PubPeer comments:
 A band appears to have been used to represent more than one experiment, after brightness contrast and aspect ratio adjusted. ***  ,