title: In vitro studies of DNA damage caused by tricyclic antidepressants: a role of peroxidase in the side effects of the drugs.
abstract: Studies show that tricyclic antidepressants prescribed for migraines, anxiety, and child enuresis have numerous adverse effects in living cells. One of the undesired outcomes observed under treatment with these drugs is DNA damage. However, the mechanisms underlying damage have yet to be elucidated. We performed in vitro studies of the DNA damage caused by four tricyclic antidepressants: imipramine, amitriptyline, opipramol, and protriptyline. We focused particularly on the DNA damage aided by peroxidases. As a model of a peroxidase, we used horseradish peroxidase (HRP). At pH 7, reactions of HRP with excess hydrogen peroxide and imipramine yielded an intense purple color and a broad absorption spectrum with the maximum intensity at 522 nm. Reactions performed between DNA and imipramine in the presence of H(2)O(2) and HRP resulted in the disappearance of the DNA band. In the case of the other three drugs, this effect was not observed. Extraction of the DNA from the reaction mixture indicated that DNA is degraded in the reaction between imipramine and H(2)O(2) catalyzed by HRP. The final product of imipramine oxidation was identified as iminodibenzyl. We hypothesize that the damage to DNA was caused by an imipramine reactive intermediate.
authors.affiliation: Science Department, John Jay College of Criminlal Justice, 445 W. 59th Avenue, New York, New York 10019, USA. ekorobkova@jjay.cuny.edu
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Korobkova
authors.forename: William
authors.initials: W
authors.lastname: Ng
authors.forename: Abhishek
authors.initials: A
authors.lastname: Venkatratnam
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Williams
authors.forename: Madina
authors.initials: M
authors.lastname: Nizamova
authors.forename: Nikolay
authors.initials: N
authors.lastname: Azar
mesh_terms: D000639:Amitriptyline / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry* / Q000633:toxicity; D002417:Cattle; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D008401:Gas Chromatography-Mass Spectrometry; D006735:Horseradish Peroxidase / Q000378:metabolism* / Q000502:physiology; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007099:Imipramine / Q000737:chemistry / Q000633:toxicity; D009888:Opipramol / Q000737:chemistry / Q000633:toxicity; D010084:Oxidation-Reduction; D011530:Protriptyline / Q000737:chemistry / Q000633:toxicity; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D011530:Protriptyline; D004247:DNA; C427203:calf thymus DNA; D006861:Hydrogen Peroxide; D009888:Opipramol; D006735:Horseradish Peroxidase; D007099:Imipramine