H2S mitigates severe acute pancreatitis through the PI3K/AKT-NF-κB pathway in vivo.

AIM: To study the effect of hydrogen sulfide (H2S) on severe acute pancreatitis (SAP) in a rat model. METHODS: Sprague-Dawley (SD) rats were administered an intraperitoneal injection of saline containing 20% L-Arg (250 mg/100 g) hourly for over 2 h to induce SAP. The rats were treated with DL-propargylglycine (PAG, 50 mg/kg) or different dosages of NaHS (5 mg/kg, 10 mg/kg, 20 mg/kg or 100 mg/kg). PAG or NaHS was administered 1 h before induction of pancreatitis. Rats were sacrificed 24 h after the last L-Arg injection. Blood and pancreas tissues were collected. RESULTS: The H2S and cystathionine-γ-lyase mRNA levels in SAP rats were significantly lower than those in the control group, and treatment with PAG further reduced the H2S level. Nevertheless, H2S was significantly increased after NaHS administration compared with the SAP group, and the degree of upregulation was associated with the NaHS dosage. NaHS reduced the levels of plasma amylase, interleukin-6 and myeloperoxidase in pancreatic tissue. NaHS suppressed the degradation of IκBα and the activity of nuclear factor-κB, as well as the phosphorylation of PI3K/AKT. CONCLUSION: H2S plays an anti-inflammatory role in SAP in vivo.