Hepatotoxicity Due to Histamine Trifluoro-Methyl Toluidide, Amthamine, R-(-)-α-Methyl Histamine and Clobenpropit (H1R-H4R-Agonists, Respectively) in Rabbit Experimental Model
Trivendra Tripathi, Aijaz Ahmed Khan, Mohammad Shahid, Haris M. Khan, Mashiatullah Siddiqui, Rahat Ali Khan and Abbas Ali Mahdi
DOI : 10.3844/amjsp.2010.1.7
Current Research in Medicine
Volume 1, Issue 1
Problem statement: Since in vivo studies looking for toxicological impact of histamine receptors-agonists in experimental models are fragmentary, the present study was designed to delineate the histopathological and biochemical changes in livers of rabbits treated with histamine receptors (H1R-H4R)-agonists. Approach: The cohort comprised of six groups (Group I control and Group II-VI treated) containing five rabbits each. Control-group received vehicle (sterile distilled water) and treated groups received subcutaneous histamine (100 µg kg-1 × b.i.d.) and H1R-agonist (HTMT dimaleate), H2R-agonist (amthamine dihydrobromide), H3R-agonist (R-(-)-α-methylhistamine dihydrobromide) and H4R-agonist (clobenpropit dihydrobromide) each in a dose of 10 µg kg-1 × b.i.d. Hepatotoxicity due to these agonists analyzed by using histopathological and biochemical methods. Results: Rabbits treated with drugs in group II-VI had significant elevated levels of serum enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin) (p<0.05). Histopathological examination revealed hepatic congestion (by histamine and H2R-agonist), centrilobular necrosis (H1R-agonist), increasing degree of binuclearity (in H4R-agonist) and rather unusual multinuclearity (in H2R-and H3R-agonist) of hepatocytes and Kupffer cell prominence (in H4R-agonist) constituted the hallmark of the injuries produced by short-term treatment by histamine and its agonists as compared to control group. Conclusion: These results provided evidence that histamine receptors on induction via their specific-agonist produce specific pattern of hepatic congestion, hepatocyte necrosis and polyploidy and Kupffer cell prominence.
© 2010 Trivendra Tripathi, Aijaz Ahmed Khan, Mohammad Shahid, Haris M. Khan, Mashiatullah Siddiqui, Rahat Ali Khan and Abbas Ali Mahdi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.