Research Article Open Access

Hepatotoxicity Due to Histamine Trifluoro-Methyl Toluidide, Amthamine, R-(-)-α-Methyl Histamine and Clobenpropit (H1R-H4R-Agonists, Respectively) in Rabbit Experimental Model

Trivendra Tripathi1, Aijaz Ahmed Khan1, Mohammad Shahid1, Haris M. Khan1, Mashiatullah Siddiqui1, Rahat Ali Khan1 and Abbas Ali Mahdi2
  • 1 Aligarh Muslim University, India
  • 2 Chhatrapati Shahuji Maharaj Medical University, India

Abstract

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.

Current Research in Medicine
Volume 1 No. 1, 2010, 1-7

DOI: https://doi.org/10.3844/amjsp.2010.1.7

Submitted On: 6 July 2009 Published On: 30 June 2010

How to Cite: Tripathi, T., Khan, A. A., Shahid, M., Khan, H. M., Siddiqui, M., Khan, R. A. & Mahdi, A. A. (2010). Hepatotoxicity Due to Histamine Trifluoro-Methyl Toluidide, Amthamine, R-(-)-α-Methyl Histamine and Clobenpropit (H1R-H4R-Agonists, Respectively) in Rabbit Experimental Model. Current Research in Medicine, 1(1), 1-7. https://doi.org/10.3844/amjsp.2010.1.7

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Keywords

  • Histamine
  • histamine receptors-agonists
  • liver histopathology
  • hepatotoxicity
  • polypoidy
  • kupffer cells