Ozdemir Ilknur, Selamoglu Talas Zeliha, Gul Mehmet, Ates Burhan, Gok Yetkin, Esrefoglu Mukaddes, Yilmaz Ismet
Department of Chemistry, Faculty of Science and Art, Inonu University, Malatya, Turkey.
Exp Anim. 2006 Oct;55(5):449-55. doi: 10.1538/expanim.55.449.
The balance between prooxidants and antioxidants is crucial to the survival and functioning of aerobic organisms. Partially reduced derivatives of oxygen, which are produced in aerobic organisms as part of normal physiological and metabolic processes, are toxic species, oxidizing numerous biomolecules, which initiate tissue injury and cell death. DMBA (7,12-dimethylbenz[a]anthracene) is a polycyclic aromatic hydrocarbon (PAH) known to cause tumors in rats. DMBA is known to generate DNA-reactive species, which may enhance oxidative stress in cells, during its metabolism. Besides the formation of DNA adducts, oxidative products derived from mutagen metabolism, such as DMBA, might impair vital cellular functions by damaging proteins and lipid membranes. Synthetic organoselenium compounds inhibit the initiation phase of carcinogenesis by inhibiting DMBA-DNA adduct formation in the target organ in vivo. Because of the health problems induced by many environmental pollutants, many efforts have been undertaken to evaluate the relative antioxidant potential of selenium and synthetic organoselenium compounds. We undertook the present study to evaluate the chemopreventive potential of the novel synthetic organoselenium compounds (1-isopropyl-3-methylbenzimidazole-2-selenone (SeI) and 1,3-di-p-methoxybenzylpyrimidine-2-selenone (SeII)) in the well-established DMBA-treated rat model by monitoring the extent of lipid peroxidation and mammary duct damage. In this study, adult female Wistar rats were treated with DMBA and the novel organoselenium compounds (SeI and SeII) in determined doses. In DMBA-treated rats, the effects of the organoselenium compounds on malondialdehyde (MDA) levels and histological changes in the rat mammary lactiferous duct were studied. The ability of the organoselenium compounds to prevent oxidative damage induced by DMBA in rat mammary ducts was demonstrated. Protection against lipid peroxidation measured as MDA in the SeI and SeII treated groups was provided by the novel synthesized organoselenium compounds. SeI and SeII both provided chemoprevention against DMBA-induced oxidative stress in the rat mammary duct.
促氧化剂和抗氧化剂之间的平衡对于需氧生物的生存和功能至关重要。作为正常生理和代谢过程的一部分，在需氧生物中产生的部分还原的氧衍生物是有毒物质，会氧化许多生物分子，引发组织损伤和细胞死亡。DMBA（7,12-二甲基苯并[a]蒽）是一种已知可在大鼠中引发肿瘤的多环芳烃（PAH）。已知DMBA在其代谢过程中会产生DNA反应性物质，这可能会增强细胞中的氧化应激。除了形成DNA加合物外，源自诱变剂代谢的氧化产物，如DMBA，可能会通过损害蛋白质和脂质膜来损害重要的细胞功能。合成有机硒化合物通过抑制体内靶器官中DMBA-DNA加合物的形成来抑制致癌作用的起始阶段。由于许多环境污染物引发的健康问题，人们已经做出了许多努力来评估硒和合成有机硒化合物的相对抗氧化潜力。我们进行了本研究，通过监测脂质过氧化程度和乳腺导管损伤情况，评估新型合成有机硒化合物（1-异丙基-3-甲基苯并咪唑-2-硒酮（SeI）和1,3-二对甲氧基苄基嘧啶-2-硒酮（SeII））在成熟的DMBA处理大鼠模型中的化学预防潜力。在本研究中，成年雌性Wistar大鼠接受了确定剂量的DMBA和新型有机硒化合物（SeI和SeII）处理。在DMBA处理的大鼠中，研究了有机硒化合物对丙二醛（MDA）水平和大鼠乳腺输乳管组织学变化的影响。新型合成有机硒化合物证明了其预防DMBA诱导的大鼠乳腺导管氧化损伤的能力。SeI和SeII处理组中以MDA衡量的脂质过氧化得到了保护。SeI和SeII均对DMBA诱导的大鼠乳腺导管氧化应激提供了化学预防作用。
