Biochemical alteration of hepatic functions by histamine H3-receptor agonist and antagonist in immunized rabbits

Abstract

Aim: The aim of our study was to investigate the functional roles of H3R agonist and antagonist in the development of hepatic functions impairment in immunized rabbits. Methods: The study comprised of six groups containing 18 rabbits in each. Group-I (negative control) and group- II (positive control) received sterile distilled water intramuscularly while Group III-VI received histamine (100 μgkg-1, s.c.), R-[-]-α-methylhistamine (H3R-agonist, 10 μgkg-1, s.c.), iodophenpropit (H3R-antagonist, 1 μgkg-1, i.m.), and the combination of iodophenpropit (1 μgkg-1, i.m.) plus histamine (100 μgkg-1, s.c.), respectively, b.i.d. (12 hours [8 am and 8 pm]) for 10 days. Groups II-VI were immunized on day 3 with intravenous injection of sheep red blood cells (1×109 cells/ml). Results: On each experimental day, the mean values of serum enzymes and bilirubin in group-I and group-II showed no changes while in groups III, IV, V, and VI, these enzymes and bilirubin levels showed significant changes (p<0.05), when compared with their values within the group. Profile of ALT and AST production revealed that ALT and AST levels moderately were changed due to degeneration of the liver. Conclusion: Our results suggest that R-[-]-α-methylhistamine showed moderate, and histamine and iodophenpropit showed mild degeneration of liver functions; while iodophenpropit plus histamine showed hepatic functions similar to control group. This study suggests that H3R antagonist in combination with histamine may be a non-toxic therapeutic target for histamine research.