title: Biochemical and histopathological evaluation of histamine receptors (H1R, H2R, H3R and H4R)-agonist in rabbits.
abstract: The present study was designed to investigate the biochemical and histopathological changes in the livers of rabbits treated with histamine and histamine receptors (H1R-H4R)-agonist. The cohort comprised of six groups containing five rabbits each. Control group received sterile distilled water (1 mL/kg × b.i.d.) and treated groups received subcutaneous histamine (100 μg/kg × b.i.d.) and H1R-H4R-agonist (histamine trifluoro-methyl toluidide, amthamine, R-[-]-α-methylhistamine, clobenpropit, respectively) each in a dose of 10 μg/kg × b.i.d. (12 h [8 am and 8 pm]) for 30 days. Hepatotoxicity due to these agonists was analyzed using biochemical and histopathological methods. Histamine and H1R-H3R-agonist were found to be hepatotoxic as shown by statistically significant (p < 0.05) elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), most marked in the H3R-agonist group. However, their levels in H4R-agonist group remained very similar to the control group. The entire drug treated groups as compared to control showed significant elevated levels of alkaline phosphatase (ALP). Histopathological examination revealed obvious changes in histamine, H2R- and H3R-agonist groups in terms of alteration of hepatic microstructure, congestion, focal necrosis and increased incidence of multinucleate hepatocytes while H1R and H4R groups showed minimal changes. From the findings of the present study it may be concluded that on repeated administration, histamine and HR-agonists-induced hepatotoxicity which is most pronounced with H3R-agonist though not severe enough to jeopardize the vital functions of liver and warrants further long-term studies.
authors: Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh 202 002, UP, India.
authors: Trivendra
authors: T
authors: Tripathi
authors: Aijaz Ahmed
authors: AA
authors: Khan
authors: Mohammad
authors: M
authors: Shahid
authors: Haris M
authors: HM
authors: Khan
authors: Mashiatullah
authors: M
authors: Siddiqui
authors: Rahat Ali
authors: RA
authors: Khan
authors: Abbas Ali
authors: AA
authors: Mahdi
authors: Abida
authors: A
authors: Malik
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006632:Histamine / Q000633:toxicity*; D017442:Histamine Agonists / Q000633:toxicity*; D008024:Ligands; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D011817:Rabbits; D011968:Receptors, Histamine / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000378:metabolism; D011970:Receptors, Histamine H2 / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000378:metabolism
chemical_list: D017442:Histamine Agonists; D008024:Ligands; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D006632:Histamine