title: Hepatoprotective, antinociceptive and antioxidant activities of cimetidine, ranitidine and famotidine as histamine H2 receptor antagonists.
abstract: The antioxidant, antinociceptive and hepatoprotective effects of H(2) receptor blockers were examined with different experimental models. Antioxidant activities were determined by employing various in vitro assay systems such as 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical-scavenging activity assays, reducing power determination assays, nitric oxide-scavenging activity assays and hydrogen peroxide-scavenging activity assays. Antinociceptive effects were determined using the hot plate test in mice. The hepatoprotective effects of cimetidine, ranitidine and famotidine against hepatotoxicity induced by carbon tetrachloride (CCl(4) ) were determined by measuring the levels of serum enzymes alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities in mice. We found that the IC(50) values of cimetidine, ranitidine and famotidine on DPPH radical-scavenging activity were 671±28, 538±21 and 955±43 μg/mL, respectively. Famotidine showed very strong nitric oxide-scavenging activity. All three compounds showed very weak hydrogen peroxide-scavenging activity. Moreover, the compounds did not exhibit any reducing power activity until concentrations of 1.6 mg/mL. All compounds also showed a dose-dependent and marked analgesic activity in mice relative to controls. Pretreatment of mice with cimetidine, ranitidine or famotidine for three consecutive days reduced CCl(4)-induced hepatotoxicity in mice. Treatment with 200 mg/kg ranitidine reduced AST, AST and ALP serum levels, while 200 and 40 mg/kg of cimetidine and famotidine, respectively, reduced AST and ALP serum levels. H(2) blockers exhibited varying levels of antioxidant activities in various assays. Our results indicate that the antioxidant activities of H(2) blockers have an analgesic activity and protective effect on CCl(4)-induced hepatotoxicity in mice. These effects were greater with ranitidine than with the other compounds.
authors.affiliation: Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Ahmadi
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Ebrahimzadeh
authors.forename: Saeb
authors.initials: S
authors.lastname: Ahmad-Ashrafi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Karami
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Mahdavi
authors.forename: Seyed Soheil Saeedi
authors.initials: SS
authors.lastname: Saravi
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002251:Carbon Tetrachloride; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015738:Famotidine / Q000008:administration & dosage / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology; D011899:Ranitidine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000975:Antioxidants; D006635:Histamine H2 Antagonists; D020011:Protective Agents; D015738:Famotidine; D002927:Cimetidine; D011899:Ranitidine; D002251:Carbon Tetrachloride