S -Propargyl-cysteine prevents concanavalin A-induced immunological liver injury in mice

Abstract

Context S -Propargyl-cysteine (SPRC), an endogenous H 2 S modulator, exerts anti-inflammatory effects on cardiovascular and neurodegenerative disease, but it remains unknown whether SPRC can prevent autoimmune hepatitis. Objective To evaluate the preventive effect of SPRC on concanavalin A (Con A)-induced liver injury and uncover the underlying mechanisms. Materials and methods Mice were randomly divided into five groups: control, Con A, SPRC (5 and 10 mg/kg injected intravenously once a day for 7 days), and propargylglycine (PAG; 50 mg/kg injected intraperitoneally 0.5 h before SPRC for 7 days). All mice except the controls were intravenously injected with Con A (20 mg/kg) on day 7. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were evaluated using kits. Inflammatory cytokines (TNF-α and IFN-γ) in the blood and in the liver were detected by ELISA Kit and real-time PCR, respectively. The expression of mitogen-activated protein kinase (MAPK) pathway proteins (p-JNK and p-Akt) and apoptosis proteins (Bax and Bcl-2) was detected using western blotting. Results SPRC reduced the levels of AST ( p < 0.05) and ALT ( p < 0.01) and decreased the release of the inflammatory cytokines. Mechanistically, SPRC increased H 2 S level ( p < 0.05) and promoted cystathionine γ-lyase (CSE) expression ( p < 0.05). SPRC inhibited the MAPK pathway activation and the apoptosis pathway. All the effects of SPRC were blocked by the CSE inhibitor PAG. Conclusions SPRC prevents Con A-induced liver injury in mice by promoting CSE expression and producing endogenous H 2 S. The mechanisms include reducing the release of inflammatory cytokines, attenuating MAPK pathway activation, and alleviating apoptosis.

Garcinone E Mitigates Oxidative Inflammatory Response and Protects against Experimental Autoimmune Hepatitis via Modulation of Nrf2/HO-1, NF-κB and TNF-α/JNK Axis

“…Following Con-A injection, Kupffer cells and T cells are greatly activated and infiltered in hepatic tissue causing immunological liver damage [ 7 , 41 , 42 ]. These cells over-secrete ROS, ILs, and TNF-α which binds to TNF- receptor-1 existing in the hepatocytes, leading to the activation of various signal transduction-linked proteins such as JNK that modulates the survival or death of hepatocytes during the inflammatory reaction [ 50 ]. An earlier study has shown that JNK-deficient mice are resistant to Con-A-caused hepatitis [ 51 ].…”

Endocrine effects of three common gas signaling molecules in humans: A literature review

“…It was found that the level of S-adenosylmethionine (AdoMet) in the brains of patients was 0.18 ± 0.04 nmol/mg, which was much lower than the normal level of 0.52 ± 0.07 nmol/mg. This was due to the low level of AdoMet in the brains of AD patients, which affected CBS activity and thus reduced the synthesis of H 2 S. In a severe AD model, H 2 S supply reduced Ab deposition, hyperphosphorylation of p-APP (the precursor protein of Ab) and Tau isoforms, and the inflammatory response to improve cognitive activity (52). This provides a new idea for the mechanism of the protective effect of H 2 S on AD.…”

Hydrogen sulfide attenuates lung injury instigated by Bisphenol-A via suppressing inflammation and oxidative stress

“…H 2 S's therapeutic potential for respiratory disorders has recently attracted a lot of attention. In obstructive respiratory illness, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung damage [ 10 ], liver inflammation [ 11 ], diabetic cardiomyopathy [ 12 ], and anti-cancer [ 13 ], H 2 S is an essential treatment component. We anticipated that H 2 S may modulate ROS formation, as well as metalloproteinases and adhesion molecule expression responses, MAP kinase signaling, and the release and attraction of inflammatory mediators in BPA-induced lung injury.…”