Immunological, biochemical and histopathological evaluation of histamine receptors (H1R, H2R, H3R and H4R)-antagonist in rabbit experimental model: A short term study

• Published in: Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie Vol. 64; no. 3; pp. 259 - 266
• Main Authors: Tripathi, Trivendra, Khan, Aijaz Ahmed, Shahid, Mohammad, Khan, Haris M., Siddiqui, Mashiatullah, Khan, Rahat Ali, Mahdi, Abbas Ali
• Format: Journal Article
• Language: English
• Published: Munich Elsevier GmbH 01.03.2012; Elsevier
• Subjects: Animal models; Animals; Bilirubin; Biological and medical sciences; blood serum; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - pathology; dimethyl sulfoxide; Enzyme-Linked Immunosorbent Assay; enzymes; Female; functional status; Hepatocytes; hepatotoxicity; Histamine; Histamine Antagonists - immunology; Histamine Antagonists - toxicity; Histamine receptors; Histamine receptors-antagonists; histopathology; Immunoglobulin G; Immunoglobulin M; Inflammation; Intravenous administration; intravenous injection; Investigative techniques, diagnostic techniques (general aspects); Kupffer cells; Liver; Liver - drug effects; Liver - immunology; Liver - pathology; Liver histopathology; Male; Medical sciences; Multinucleate hepatocytes; Necrosis; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Rabbits; Ranitidine; receptors; Serum enzymes; Liver histopathology; Histamine; Multinucleate hepatocytes; Serum enzymes; Histamine receptors-antagonists; Short term; Evaluation; Animal model; Digestive system; Enzyme; Liver; Rabbit; Model study; Biochemistry; Lagomorpha; Experimental study; Vertebrata; Anatomic pathology; Mammalia; Histopathology; Hepatocyte; Serum; Antagonist; Biological receptor
• ISSN: 0940-2993; 1618-1433
• DOI: 10.1016/j.etp.2010.08.018

The present study was designed to delineate the immuno- and hepatotoxicological roles of HRs-antagonists in vivo which is elementary in existing literature. The cohort comprised of two experimental studies. Experimental study 1 was designed for immunological investigations and consisted of seven groups and immunized with intravenous injection of SRBC at day 3 containing six rabbits each. Experimental study 2 was designed to assess the functional status of liver and comprised of seven groups containing five rabbits each. In both experimental studies group-I received sterile distilled water intramuscularly, and group II–VI received subcutaneous histamine, pheniramine (H1R-antagonist), ranitidine (H2R-antagonist), iodophenpropit (H3R-antagonist) and JNJ7777120 (H4R-antagonist), respectively while group-VII received DMSO intramuscularly. ELISA was used to assess the immunological investigations. The SRBC-specific immunoglobulins (Igs), IgM and IgG were significantly increased (p<0.05). Hepatotoxicity due to same histamine and HRs-antagonists were demonstrated by biochemical and histopathological methods. Rabbits in group II–VI had significantly (p<0.05) elevated levels of serum enzymes (ALT, AST, ALP) and bilirubin. Histopathological examination showed maintained hepatic lobular architecture in histamine and DMSO-treated groups a kin to control. Notable findings in other groups included increased binuclearity in H1R, trinuclearity in H2R, oxyphilic clusters of hepatocytes in H3R and moderate centrilobular necrosis in H3R and H4R-antagonist-treated groups without obvious inflammatory cell infiltration and Kupffer cell prominence. It is concluded that HRs-antagonist play immune suppressive role through H1R, H2R and H4R while immune enhancing role through H3R. In addition, HRs-antagonists appear moderately hepatotoxic in terms of altered serum enzyme levels and non-inflammatory hepatocellular damage.