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


CONCLUSIONS
H2S plays an anti-inflammatory role in SAP in vivo.
Chun-Yan Rao, Lan-Ying Fu, Dai-Xing Chen, Tian Gan, Xiao-Yan Zhao, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Chun-Yan
CY
Rao
Chun-Yan Rao, Lan-Ying Fu, Dai-Xing Chen, Tian Gan, Xiao-Yan Zhao, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Lan-Ying
LY
Fu
Chun-Yan Rao, Lan-Ying Fu, Dai-Xing Chen, Tian Gan, Xiao-Yan Zhao, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Chang-Lun
CL
Hu
Chun-Yan Rao, Lan-Ying Fu, Dai-Xing Chen, Tian Gan, Xiao-Yan Zhao, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Dai-Xing
DX
Chen
Chun-Yan Rao, Lan-Ying Fu, Dai-Xing Chen, Tian Gan, Xiao-Yan Zhao, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Tian
T
Gan
Chun-Yan Rao, Lan-Ying Fu, Dai-Xing Chen, Tian Gan, Xiao-Yan Zhao, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Yi-Cheng
YC
Wang
Chun-Yan Rao, Lan-Ying Fu, Dai-Xing Chen, Tian Gan, Xiao-Yan Zhao, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Xiao-Yan
XY
Zhao
D000480:Alkynes / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001120:Arginine; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019610:Cytoprotection; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000097:blood / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology*
D000480:Alkynes; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D016328:NF-kappa B; D013440:Sulfides; C009055:propargylglycine; D001120:Arginine; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D003542:Cystathionine gamma-Lyase; C025451:sodium bisulfide; D005998:Glycine
Cystathionine-γ-lyase; Cytokine; Hydrogen sulfide; Severe acute pancreatitis; Signaling pathway