Role of hydrogen sulfide in acute pancreatitis and associated lung injury.

Abstract

Hydrogen sulfide (H2S) is a naturally occurring gas with potent vasodilator activity. Cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS) utilize L-cysteine as substrate to form H2S. Of these two enzymes, cystathionine-gamma-lyase (CSE) is believed to be the key enzyme that forms H2S in the cardiovascular system. Whilst H2S has been reported to relax precontracted rat arteries in vitro and to lower blood pressure in the rat, its effect in an inflammatory condition such as acute pancreatitis has not previously been reported. In this paper, we report the presence of H2S synthesizing enzyme activity and CSE (as determined by mRNA signal) in the pancreas. Also, prophylactic, as well as therapeutic, treatment with the CSE inhibitor, DL-propargylglycine (PAG), significantly reduced the severity of caerulein-induced pancreatitis and associated lung injury, as determined by 1) hyperamylasemia [plasma amylase (U/L) (control, 1204+/-59); prophylactic treatment: placebo, 10635+/-305; PAG, 7904+/-495; therapeutic treatment: placebo, 10427+/-470; PAG, 7811+/-428; P<0.05 PAG c.f. placebo; n=24 animals in each group]; 2) neutrophil sequestration in the pancreas [pancreatic myeloperoxidase oxidase (MPO) activity (fold increase over control) (prophylactic treatment: placebo, 5.78+/-0.63; PAG, 2.97+/-0.39; therapeutic treatment: placebo, 5.48+/-0.52; PAG, 3.03+/-0.47; P<0.05 PAG c.f. placebo; n=24 animals in each group)]; 3) pancreatic acinar cell injury/necrosis; 4) lung MPO activity (fold increase over control) [prophylactic treatment: placebo, 1.99+/-0.16; PAG, 1.34+/-0.14; therapeutic treatment: placebo, 2.03+/-0.12; PAG, 1.41+/-0.97; P<0.05 PAG c.f. placebo; n=24 animals in each group]; and 5) histological evidence of lung injury. These effects of CSE blockade suggest an important proinflammatory role of H2S in regulating the severity of pancreatitis and associated lung injury and raise the possibility that H2S may exert similar activity in other forms of inflammation.

• Authors: Madhav Bhatia, Fei Ling Wong, Di Fu, Hon Yen Lau, Shabbir M Moochhala, Philip K Moore
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 19 Issue 6 Pg. 623-5 (Apr 2005) ISSN: 1530-6860 [Electronic] United States
• PMID: 15671155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Enzyme Inhibitors
• Placebos
• RNA, Messenger
• propargylglycine
• Peroxidase
• Amylases
• Cystathionine beta-Synthase
• Cystathionine gamma-Lyase
• Cysteine
• Glycine
• Hydrogen Sulfide

Topics

• Acute Disease
• Alkynes (pharmacology, therapeutic use)
• Amylases (blood)
• Animals
• Cystathionine beta-Synthase (metabolism)
• Cystathionine gamma-Lyase (genetics, metabolism)
• Cysteine (metabolism)
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Glycine (analogs & derivatives, pharmacology, therapeutic use)
• Hydrogen Sulfide (blood, metabolism)
• Lung Diseases (etiology, pathology, prevention & control)
• Male
• Mice
• Mice, Inbred BALB C
• Pancreas (enzymology)
• Pancreatitis (etiology, pathology, prevention & control)
• Peroxidase (metabolism)
• Placebos
• RNA, Messenger (analysis)
• Vasodilation (drug effects)