Tripathi Trivendra, Khan Aijaz Ahmed, Shahid Mohammad, Khan Haris M, Siddiqui Mashiatullah, Khan Rahat Ali, Mahdi Abbas Ali
Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh 202 002, UP, India.
Exp Toxicol Pathol. 2012 Mar;64(3):259-66. doi: 10.1016/j.etp.2010.08.018. Epub 2010 Sep 25.
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.
本研究旨在阐明组胺受体拮抗剂在体内的免疫和肝毒理学作用，这在现有文献中尚属基础内容。该队列包括两项实验研究。实验研究1旨在进行免疫学研究，分为七组，于第3天通过静脉注射SRBC进行免疫，每组六只兔子。实验研究2旨在评估肝脏的功能状态，分为七组，每组五只兔子。在两项实验研究中，第一组肌肉注射无菌蒸馏水，第二至六组分别皮下注射组胺、苯海拉明（H1R拮抗剂）、雷尼替丁（H2R拮抗剂）、碘苯丙哌嗪（H3R拮抗剂）和JNJ7777120（H4R拮抗剂），而第七组肌肉注射二甲基亚砜（DMSO）。采用酶联免疫吸附测定（ELISA）评估免疫学研究。SRBC特异性免疫球蛋白（Igs）、IgM和IgG显著增加（p<0.05）。通过生化和组织病理学方法证实了相同组胺和组胺受体拮抗剂引起的肝毒性。第二至六组兔子的血清酶（ALT、AST、ALP）和胆红素水平显著升高（p<0.05）。组织病理学检查显示，组胺和DMSO处理组的肝小叶结构与对照组相似。其他组的显著发现包括H1R拮抗剂处理组双核细胞增多、H2R拮抗剂处理组三核细胞增多、H3R拮抗剂处理组肝细胞嗜酸性簇以及H3R和H4R拮抗剂处理组中度中央小叶坏死，且无明显炎症细胞浸润和库普弗细胞增生。结论是，组胺受体拮抗剂通过H1R、H2R和H4R发挥免疫抑制作用，而通过H3R发挥免疫增强作用。此外，就血清酶水平改变和非炎性肝细胞损伤而言，组胺受体拮抗剂似乎具有中度肝毒性。
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