title: Enhancing effect of cimetidine on peroxidase activity of human erythrocyte hemoglobin.
abstract: BACKGROUND
  Hemoglobin is released to the serum after erythrocyte lyses. Haptoglobin is responsible for carrying hemoglobin into the serum. In hemolytic disease, the amount of hemoglobin which is released to the serum is high; however, the amount of haptoglobin is not enough for binding all the released hemoglobins. Free hemoglobin has peroxidase activity (a pseudoenzyme) and has been indicated to be harmful for patients. This study is focused on the effect of cimetidine on peroxidase activity of hemoglobin.
  
  
  METHODS
  Erythrocytes were lysed to obtain hemoglobin. Peroxidase activity of hemoglobin was detected using o-dianisidine and H(2)O(2) as substrates.
  
  
  RESULTS
  Our results showed that the drug operated as an activator for the pseudoenzyme. Cimetidine bound to the pseudoperoxidase in an un-competitive manner and decreased the Km. Half maximal effective concentration (EC(50)) of cimetidine was determined to be about 12.5 mM. Alkaline pH increased the rate of reaction. Arrhenius plot showed that the activation energies of reactions in the absence and presence of drug were about 10.5 kJ/mol and 7.65 kJ/mol, respectively.
  
  
  CONCLUSIONS
  The results demonstrated that cimetidine activates the peroxidase activity of free hemoglobin. Hence, it is suggested that the prescription of cimetidine for the patients with hemolyses diseases may enhance the harmful effects of free hemoglobin in these patients.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Delasoud
authors.forename: Dariush
authors.initials: D
authors.lastname: Minai-Tehrani
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Mollasalehi
mesh_terms: D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D055162:Biocatalysis / Q000187:drug effects; D002927:Cimetidine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006441:Hemoglobin A / Q000819:agonists / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010544:Peroxidases / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature
chemical_list: D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D002927:Cimetidine; D006441:Hemoglobin A; D010544:Peroxidases