PMID: 7538432Feb 1, 1994Paper

Diltiazem and superoxide dismutase modulate hepatic acute phase response in gram-negative sepsis

Shock
S RoseM M Sayeed

Abstract

This study assessed the hepatic acute phase response and cellular Ca2+ regulation in septic animals and in hepatoma cell lines in vitro. Sepsis was induced in male Sprague-Dawley rats by implanting in their abdominal cavities fecal pellets impregnated with live Escherichia coli and Bacteroides fragilis. 8 h after implantations, rats were treated with diltiazem (1.2 mg/kg) or superoxide dismutase (SOD) (5 x 10(3) units/kg). After 24 h, plasma acute phase proteins (APP) were determined by immunoelectrophoresis, and hepatic APP-mRNAs by Northern blot hybridization. Effects of diltiazem, verapamil, or SOD on hepatic cells were determined in rat Reuber H-35 and human HepG2 hepatoma cells. Sepsis induced a significant increase in plasma APP and their hepatic mRNAs. Diltiazem and SOD reduced the sepsis-induced elevations in plasma lactate, the febrile response and mortality. APP expression in H-35 and HepG2 cells, stimulated by interleukin 1 (IL-1), IL-6, and dexamethasone, was inhibited by diltiazem or verapamil but not SOD. The results suggest that a heightened hepatic APP response in septic animals accompanies systemic/metabolic derangements and a significant animal mortality. Because diltiazem was previously shown to prevent sepsi...Continue Reading

Citations

Mar 21, 1998·Critical Care Medicine·R S Hotchkiss, I E Karl
Dec 17, 2009·Pathology·Rajkumar CheluvappaDavid G Le Couteur
Jul 9, 2010·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Rajkumar CheluvappaDavid G Le Couteur
Jun 1, 2004·Journal of Applied Physiology·Xizhong CuiPeter Q Eichacker
Jun 5, 2017·Redox Biology·Andrey V KozlovAdelheid Weidinger

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