Lycopene Alleviates Chronic Stress-Induced Liver Injury by Inhibiting Oxidative Stress-Mediated Endoplasmic Reticulum Stress Pathway Apoptosis in Rats

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.

EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25/Keap1/Nrf2 axis

“…These results suggest that ERS may be a potential mechanism of AEC senescence in IPF. Oxidative stress is one of the major drivers of protein homeostasis imbalance, which can lead to an increase in the number of unfolded proteins in the ER lumen, which in turn induces ERS [ 67 ]. Our previous study found that inhibition of EETs degradation has the ability to reduce the level of oxidative stress in the lungs [ 14 ].…”

Potential Hepatoprotective Effects of Chamaecyparis lawsoniana against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation

“…Subsequently, this process triggers the activation of cleaved caspase3, initiating cell degradation [116]. This process holds a significant importance in the context of liver injury [117] since evidence suggested that the p53 protein accumulates in individuals with various inflammatory liver diseases. Inhibiting the p53 signaling pathway has been demonstrated to enhance drug-induced hepatocyte injury by regulating the mitochondrial apoptosis pathway.…”

Chlorogenic Acid Alleviates Chronic Stress-Induced Intestinal Damage by Inhibiting the P38MAPK/NF-κB Pathway

“…SB203580 was solubilized in a combined solution made up of 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline. 22 All rats were fasted from food and water during the experiment (9:00−15:00). The body weight of the rats was checked every 3 days, and the amount of food taken by the rats was recorded daily.…”

“…The CS + SB203580 group rats were given SB203580 (0.5 mg/kg, intraperitoneal injection, HY-10256, Med Chem Express, USA) 1 h before restraint stress every other day. SB203580 was solubilized in a combined solution made up of 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline . All rats were fasted from food and water during the experiment (9:00–15:00).…”