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Lycopene Alleviates Chronic Stress-Induced Liver Injury by Inhibiting Oxidative Stress-Mediated Endoplasmic Reticulum Stress Pathway Apoptosis in Rats.
- Source :
-
Journal of agricultural and food chemistry [J Agric Food Chem] 2022 Nov 16; Vol. 70 (45), pp. 14414-14426. Date of Electronic Publication: 2022 Nov 01. - Publication Year :
- 2022
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Abstract
- The liver is the major organ of metabolism and is extremely vulnerable to chronic stress. Lycopene (LYC) is a natural carotenoid with potent antioxidant and chronic disease potential. However, whether LYC protects against chronic restraint stress (CRS)-induced liver injury and the underlying mechanisms remain unclear. In this study, rats were restrained for 21 days for 6 h per day, with or without gavage of LYC (10 mg/kg). Serum ALT (85.99 ± 4.07 U/L) and AST (181.78 ± 7.35 U/L) and scores of liver injury were significantly increased in the CRS group. LYC significantly promoted the nuclear translocation of Nrf2, elevated the expression of antioxidant genes, and attenuated reactive oxygen radicals (ROS) levels within the liver. Cellular thermal shift assay (CETSA) and molecular docking results indicated that LYC competitively binds to Keap1 with the lowest molecule affinity of -9.0 kcal/mol. Moreover, LYC significantly relieved the hepatic endoplasmic reticulum swelling and decreased the expression of endoplasmic reticulum stress (ERS) hallmarks like GRP78, CHOP, and cleaved caspase-12. Meanwhile, LYC also mitigated CRS-induced hepatocyte apoptosis. Interestingly, every other day, the intraperitoneal injection of the Nrf2 inhibitor brusatol (0.4 mg/kg) significantly counteracted the protective effect of LYC. In conclusion, LYC protects against CRS-induced liver injury by activating the Nrf2 signaling pathway, scavenging ROS, and further attenuating ERS-associated apoptosis pathways.
- Subjects :
- Rats
Animals
Lycopene metabolism
Endoplasmic Reticulum Stress
Kelch-Like ECH-Associated Protein 1 genetics
Kelch-Like ECH-Associated Protein 1 metabolism
Reactive Oxygen Species metabolism
Antioxidants metabolism
Molecular Docking Simulation
Oxidative Stress
Apoptosis
NF-E2-Related Factor 2 genetics
NF-E2-Related Factor 2 metabolism
Chemical and Drug Induced Liver Injury, Chronic etiology
Chemical and Drug Induced Liver Injury, Chronic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5118
- Volume :
- 70
- Issue :
- 45
- Database :
- MEDLINE
- Journal :
- Journal of agricultural and food chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 36318656
- Full Text :
- https://doi.org/10.1021/acs.jafc.2c06650