title: Cardioprotective role of H₃R agonist imetit on isoproterenol-induced hemodynamic changes and oxidative stress in rats.
abstract: The cardioprotective role of histamine H3 receptor (H3R) agonist imetit (IMT) in isoproterenol (ISO)-induced alterations of hemodynamic and oxidative stress was investigated in Wistar rats. In this study, rats were treated with IMT (5 and 10 mg/kg, per orally [p.o.]), carvedilol (10 mg/kg, p.o.) and ISO control group (normal saline) for 7 d, with concurrent subcutaneous administration of ISO (85 mg/kg) at 24 h interval on last two consecutive days whereas control group was administered with vehicle only. ISO significantly attenuated cardiac antioxidant enzymes superoxide dismutase, catalase and increased plasma cardiac injury biomarkers creatine kinase-MB, alanine transaminase and aspartate transaminase. ISO also altered cardiac activity as evidenced by decrease in blood pressure (34.60%) and increase in heart rate (11.40%). The damage due to oxidative stress was revealed by histopathology alterations such as myocyte necrosis, myofibrillar degeneration and pyknotic nucleus. However, pre-treatment with IMT demonstrated restoration of hemodynamic alterations along with significant preservation of antioxidants and myocyte injury-specific marker enzymes. Furthermore, protective effect of IMT was reconfirmed by the histopathological salvage of myocardium. Results of the present study demonstrated the cardioprotective potential of IMT, as evidenced by favorable improvement in ISO-induced hemodynamic, plasma cardiac biomarkers and tissue antioxidant status along with maintenance of integrity of myocardium.
authors.affiliation: a Faculty of Pharmacy, Department of Pharmacology, Jamia Hamdard , Hamdard University , New Delhi , India and.
authors.forename: Chander Hass
authors.initials: CH
authors.lastname: Yadav
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
authors.forename: Mohd
authors.initials: M
authors.lastname: Akhtar
authors.forename: Razia
authors.initials: R
authors.lastname: Khanam
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D001827:Body Height / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000077261:Carvedilol; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D017442:Histamine Agonists / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D000975:Antioxidants; D015415:Biomarkers; D002227:Carbazoles; D002316:Cardiotonic Agents; D017442:Histamine Agonists; D007093:Imidazoles; D011412:Propanolamines; D000077261:Carvedilol; C077430:imetit; D013890:Thiourea; D007545:Isoproterenol
keywords: Antioxidant; cardiac biomarkers; hemodynamic measurement; imetit; isoproterenol