Protective mechanism of quercetin compounds against acrylamide-induced hepatotoxicity

Linzi Li; Xueying Lei; Lin Chen; Ya Ma; Jun Luo; Xuebo Liu; Xinglian Xu; Guanghong Zhou; Xianchao Feng

doi:10.26599/FSHW.2022.9250019

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Protective mechanism of quercetin compounds against acrylamide-induced hepatotoxicity

Linzi Li^{^a^,¹}, Xueying Lei^{^a^,¹}, Lin Chen^{^a}(), Ya Ma^{^a}, Jun Luo^{^b}, Xuebo Liu^{^a}, Xinglian Xu^{^c}, Guanghong Zhou^{^c}, Xianchao Feng^{^a}()

College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China

College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China

Synergetic Innovation Center of Food Safety and Nutrition, Key Laboratory of Meat Processing and Quality Control, Ministry of Education, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China

¹ These authors contributed equally.

Peer review under responsibility of Tsinghua University Press.

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Highlights

• Quercetin compounds can attenuate liver injury induced by AA, reduce venous congestion and inflammatory infiltration.

• Quercetin compounds attenuate AA induced liver oxidative stress by affecting ROS level.

• Akt/mTOR signaling pathway is activated to affect LC3 transformation and autophagy formation.

• Reverse the activity of caspase-9 and Caspase-3 and increase the ratio of Bax/Bcl-2.

• reverse the activation of IRE1-xbp1 pathway and increase the expression of CHOP protein.

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Abstract

Quercetin compounds have antioxidant, anti-inflammatory and anticancer pharmacological functions. Longterm exposure to acrylamide (AA) can cause liver injury and endanger human health. However, whether quercetin compounds can attenuate AA-induced liver injury and the specific mechanism are not clear. Here, we studied the mechanism and structure-activity relationship of quercetin compounds in reducing AA-induced hepatotoxicity in vivo and in vitro. In vivo studies found that quercetin-like compounds protect against AA-induced liver injury by reducing oxidative stress levels, activating the Akt/mTOR signaling pathway to attenuate autophagy, and improving mitochondrial apoptosis and endoplasmic reticulum stress-mediated apoptosis. In vitro studies found that quercetin compounds protected HepG2 cells from AA by attenuating the activation of AA-induced autophagy, lowering reactive oxygen species (ROS) levels by exerting antioxidant effects and thus attenuating oxidative stress, increasing mitochondrial membrane potential (MMP), and improving apoptosis-related proteins, thus attenuating AA-induced apoptosis. Furthermore, the conformational differences between quercetin compounds correlated with their protective capacity against AA-induced hepatotoxicity, with quercetin showing the best protective capacity due to its strongest antioxidant activity. In conclusion, quercetin compounds can protect against AA-induced liver injury through multiple pathways of oxidative stress, autophagy and apoptosis, and their protective capacity correlates with antioxidant activity.

Keywords

Quercetin compounds Acrylamide Protection mechanism Oxidative stress Antioxidant activity

References

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