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LIVER AND BILIARY TRACT

Impaired cytoprotective function of muscle in human gallbladders with cholesterol stones

Department of Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island

Submitted 15 June 2004 ; accepted in final form 6 October 2004

Acute cholecystitis develops in gallbladders (GB) with excessive bile cholesterol (Ch). Increased membrane Ch content affects membrane function and may affect PGE₂ receptors involved in the cytoprotection against acute inflammation. This study was aimed at determining whether the cytoprotective response to PGE₂ is affected by lithogenic bile with Ch. Muscle cells from human GB with cholesterol stones (ChS) or pigment stones (PS) were obtained by enzymatic digestion. PGE₂ levels were measured by radioimmunoassay, and activities of superoxide dismutase (SOD) and catalase were assayed by spectrophotometry. The contraction in response to H₂O₂ in muscle cells from PS was 14 ± 0.3%, not different from normal controls, and decreased after the cells were incubated with Ch-rich liposomes (P < 0.05), which increase the Ch content in the plasma membranes. In muscle cells from GB with ChS, H₂O₂-induced contraction was only 9.2 ± 1.3% and increased to 14 ± 0.2% after Ch-free liposome treatment to remove Ch from the plasma membranes (P < 0.01). H₂O₂ caused a similar increase in the levels of lipid peroxidation and PGE₂ content in muscle cells from GBs with ChS and PS. However, the activities of SOD and catalase were significantly lower in muscle cells from GBs with ChS compared with those with PS. The binding capacity of PGE₂ receptors was also significantly lower in muscle cells from GBs with ChS compared with those with PS. In conclusion, the cytoprotective response to reactive oxygen species is reduced in muscle cells from GBs with ChS despite a normal increase in the cellular levels of PGE₂. This impaired cytoprotective response may be due to a dysfunction of PGE₂ receptors with decreased binding capacity resulting from excessive Ch levels in the plasma membrane.

reactive oxygen species; free-radical scavengers; pigment stones

This article has been cited by other articles:

				P. Cong, Z.-L. Xiao, P. Biancani, and J. Behar Reactive oxygen species are messengers in maintenance of human and guinea pig gallbladder tonic contraction Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1244 - G1251. [Abstract] [Full Text] [PDF]

				P. Cong, Z.-L. Xiao, P. Biancani, and J. Behar Prostaglandins mediate tonic contraction of the guinea pig and human gallbladder Am J Physiol Gastrointest Liver Physiol, January 1, 2007; 292(1): G409 - G418. [Abstract] [Full Text] [PDF]