ABSTRACT
Nuclear factor erythroid-2 related factor 2 ( Nrf2 ) is an important nuclear transcription factor which protects cells a-gainst oxidative stress injury. Upon exposure to reactive oxygen species ( ROS) or electrophilic stress, Nrf2 can translocate into the nucleus, and then bind to the antioxidant response element ( ARE) , regulating the expression of several antioxidant enzymes and phase Ⅱ detoxifying enzymes which aimed at the detoxifica-tion and elimination of harmful exogenous chemicals, resulting in the facilitation of hepatoprotection. Oxidative stress is the com-mon pathogenesis of many liver diseases, while the Nrf2-ARE signaling pathway is extremely important in the prevention and progression of many liver diseases. Nrf2 has more recently been implicated as a new therapeutic target in treating liver diseases. Here, we focus on the most common liver diseases and the devel-opment of these conditions where activation of Nrf2 may alleviate disease progression, so as to provide reference for related re-search in the future.
ABSTRACT
Objective To investigate the effects of lipopolysaccharide(LPS) on the tryptophan-kynurenine(TRP) metabolic pathway in rat brains and provide new evidence for the relationship between inflammation and depression.Methods Rats in LPS group were given a single dose of 3.5 mg/kg LPS.while the rats in control group were given the same dosage of saline.The dialysis in ventro-hippocampus were collected by microdialysis within 8 hours and then the TRP,KYN and KA were detected by LC-MS/MS.And the expression of indoleamine 2,3-dioxygenase was detected by Western-blot.Results The level of TRP((550.15± 107.96) pmol/L) and KYN ((337.95±62.73) pmol/L) showed a time-dependent increase after administration LPS 4 h compared with the control group(TRP (368.38±59.31) pmol/L,KYN (172.80±43.96) pmol/L),while KA level in the circulation exhibited a trend to decrease,especially at 7 h ((3.47±0.62) pmol/L,P＜0.05).The ratio of KYN/TRP significantly increased at about 5 h (0.69±0.11,P＜ 0.05),and an ratio of KA/KYN (0.02±0.00) was dramatically decreased after administering LPS 4 h compared with the control group (0.05±0.01)(P＜0.05).Most of the analytes showed more dramatic changes around 4 h to 8 h.LPS group(1.48±0.37) increased the protein expression of indoleamine 2,3-dioxygenase compared with the control group(1.00±0.24) (P＜0.01).Conclusions LPS may cause tryptophan metabolic abnormalities and accelerate the way of kynurenine metabolism,leading to decreased the kynurenic acid status.