Biochemical and histopathological evaluation of histamine receptors (H1R, H2R, H3R and H4R)-agonist in rabbits.

Trivendra Tripathi, Aijaz Ahmed Khan, Mohammad Shahid, Haris M Khan, Mashiatullah Siddiqui, Rahat Ali Khan, Abbas Ali Mahdi, Abida Malik

Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh 202 002, UP, India.

Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie 2013 Mar

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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. Copyright © 2011 Elsevier GmbH. All rights reserved.

Citation

Trivendra Tripathi, Aijaz Ahmed Khan, Mohammad Shahid, Haris M Khan, Mashiatullah Siddiqui, Rahat Ali Khan, Abbas Ali Mahdi, Abida Malik. Biochemical and histopathological evaluation of histamine receptors (H1R, H2R, H3R and H4R)-agonist in rabbits. Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie. 2013 Mar;65(3):271-5