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Lipid peroxidation, detoxification capacity, and genome damage in mice after transplacental exposure to pharmaceutical drugs

Marković, Darko; Katić, Jelena; Stojković, Ranko; Borović, Suzana; Žarković, Neven; Fučić, Aleksandra (2013) Lipid peroxidation, detoxification capacity, and genome damage in mice after transplacental exposure to pharmaceutical drugs. Brazilian journal of medical and biological research, 46 (12). pp. 1014-1020. ISSN 0100-879X

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Data on genome damage, lipid peroxidation, and levels of glutathione peroxidase (GPX) in newborns after transplacental exposure to xenobiotics are rare and insufficient for risk assessment. The aim of the current study was to analyze, in an animal model, transplacental genotoxicity, lipid peroxidation, and detoxification disturbances caused by the following drugs commonly prescribed to pregnant women: paracetamol, fluconazole, 5- nitrofurantoin, and sodium valproate. Genome damage in dams and their newborn pups transplacentally exposed to these drugs was investigated using the in vivo micronucleus (MN) assay. The drugs were administered to dams intraperitoneally in three consecutive daily doses between days 12 and 14 of pregnancy. The results were correlated, with detoxification capacity of the newborn pups measured by the levels of GPX in blood and lipid peroxidation in liver measured by malondialdehyde (HPLC-MDA) levels. Sodium valproate and 5-nitrofurantoin significantly increased MN frequency in pregnant dams. A significant increase in the MN frequency of newborn pups was detected for all drugs tested. This paper also provides reference levels of MDA in newborn pups, according to which all drugs tested significantly lowered MDA levels of newborn pups, while blood GPX activity dropped significantly only after exposure to paracetamol. The GPX reduction reflected systemic oxidative stress, which is known to occur with paracetamol treatment. The reduction of MDA in the liver is suggested to be an unspecific metabolic reaction to the drugs that express cytotoxic, in particular hepatotoxic, effects associated with oxidative stress and lipid peroxidation.

Item Type: Article
Uncontrolled Keywords: glutathione peroxidase ; malondialdehyde ; genome damage ; transplacental exposure
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Genotoxicity of chemical and physical agents of natural and anthropogenic origin (Genotoksičnost kemijskih i fizikalnih agensa prirodnog i antropogenog podrijetla)-Vilena Kašuba022-0222148-2137MZOS
New therapeutic models in the treatment of malignant diseases (Novi terapijski modaliteti u liječenju malignih bolesti)-Ranko Stojković098-0982464-2390MZOS
Lipids, free radicals and their messengers in integrative oncology (Lipidi, slobodni radikali i njihovi glasnici u integrativnoj onkologiji)-Neven Žarković098-0982464-2519MZOS
Depositing User: Sofija Konjević
Date Deposited: 07 Apr 2016 12:13
DOI: 10.1590/1414-431X20132814

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