Abstract
BackgroundHydrogen sulfide (H2S) has recently been shown to play an important role in the digestive system, but the role of endogenous H2S produced locally in the gallbladder is unknown. The aim of this study was to investigate whether gallbladder possesses the enzymatic machinery to synthesize H2S, and whether H2S synthesis is changed in gallbladder inflammation during acute acalculous cholecystitis (AC).MethodsAdult male guinea pigs underwent either a sham operation or common bile duct ligation (CBDL). One, two, or three days after CBDL, the animals were sacrificed separately. Hematoxylin and eosin-stained slides of gallbladder samples were scored for inflammation. H2S production rate in gallbladder tissue from each group was determined; immunohistochemistry and western blotting were used to determine expression levels of the H2S-producing enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in gallbladder.ResultsThere was a progressive inflammatory response after CBDL. Immunohistochemistry analysis showed that CBS and CSE were expressed in the gallbladder epithelium, muscular layer, and blood vessels and that the expression increased progressively with increasing inflammation following CBDL. The expression of CBS protein as well as the H2S-production rate was significantly increased in the animals that underwent CBDL, compared to those that underwent the sham operation.ConclusionsBoth CBS and CSE are expressed in gallbladder tissues. The expression of these enzymes, as well as H2S synthesis, was up-regulated in the context of inflammation during AC.
Highlights
Acute acalculous cholecystitis (AC) is characterized by gallbladder inflammation without evidence of calculi or sludge [1]
The results of the present study demonstrate that CBS and cystathionine γ-lyase (CSE), the enzymes that catalyze the conversion of cysteine to H2S, are expressed in the gallbladder in guinea pigs
The expression of enzymes, as well as H2S synthesis, was significantly up-regulated during AC. Both CBS and CSE are expressed in the GI tract, including in the liver, stomach, small intestine, and colon [7]
Summary
Acute acalculous cholecystitis (AC) is characterized by gallbladder inflammation without evidence of calculi or sludge [1]. Common bile duct ligation (CBDL) in the guinea pig produces a histologic picture that is nearly identical to that of acute human cholecystitis, with subserosal edema, hemorrhage, white blood cell infiltration, and vasodilation [3]. This simple animal model reveals impaired gallbladder muscle contractility [2,3]. Conclusions: Both CBS and CSE are expressed in gallbladder tissues The expression of these enzymes, as well as H2S synthesis, was up-regulated in the context of inflammation during AC
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