Andric Nebojsa L, Andric Silvana A, Zoric Sonja N, Kostic Tatjana S, Stojilkovic Stanko S, Kovacevic Radmila Z
Department of Biology and Ecology, Faculty of Sciences, 21000 Novi Sad, Serbia and Montenegro.
Toxicology. 2003 Dec 15;194(1-2):65-75. doi: 10.1016/j.tox.2003.08.002.
The mechanism by which Aroclors and other polychlorinated biphenyls (PCBs) inhibit testicular androgenesis in vivo and in vitro has not been characterized. Here we studied in adult rats the effects of intratesticular (i.t.t.), intraperitoneal (i.p.) and by gavage (p.o.) administration of Pyralene, an Aroclor 1260-based transformer fluid, on testicular androgenesis and oxidative status in androgen-producing interstitial cells and liver. Pyralene markedly decreased in vitro agonist stimulated androgenesis 24 h after bilateral i.t.t.-injection (25 microg/testis), 24 h and 96 h after single i.p.-injection (10 and 50 mg/kg body weight), and 96 h after p.o.-administration (7x10 mg and 7x50 mg/kg body weight daily). Inhibited androgenesis was accompanied by changes in the activity of antioxidant enzymes (AOEs) in interstitial cells after local i.t.t.-treatment and occasionally after systemic Pyralene application. Among changes in the activity, glutathione peroxidase and catalase reflected relatively well the toxicity of Pyralene in these cells. In liver, glutathione-S-transferase (GST) and glutathione peroxidase activities were enhanced after p.o.-treatment and total glutathione (tGSH) content and lipid peroxidation (LP) were enhanced after i.p.-administration. These results indicate that Pyralene inhibits androgenesis independently of the method of its administration. The results also suggest that changes in the oxidative status in testicular milieu are not critical for Pyralene-induced inhibition of androgenesis.
多氯联苯混合物(Aroclors)和其他多氯联苯(PCBs)在体内和体外抑制睾丸雄激素生成的机制尚未明确。在此,我们研究了在成年大鼠中,经睾丸内(i.t.t.)、腹腔内(i.p.)和灌胃(p.o.)给予Pyralene(一种基于Aroclor 1260的变压器油)对雄激素生成间质细胞和肝脏中睾丸雄激素生成及氧化状态的影响。双侧睾丸内注射(25微克/睾丸)24小时后、单次腹腔注射(10和50毫克/千克体重)24小时和96小时后以及灌胃给药(每天7×10毫克和7×50毫克/千克体重)96小时后,Pyralene显著降低了体外激动剂刺激的雄激素生成。局部睾丸内给药后以及偶尔全身应用Pyralene后,抑制雄激素生成伴随着间质细胞中抗氧化酶(AOEs)活性的变化。在这些活性变化中,谷胱甘肽过氧化物酶和过氧化氢酶相对较好地反映了Pyralene对这些细胞的毒性。在肝脏中,灌胃处理后谷胱甘肽 - S - 转移酶(GST)和谷胱甘肽过氧化物酶活性增强,腹腔注射后总谷胱甘肽(tGSH)含量和脂质过氧化(LP)增强。这些结果表明,Pyralene抑制雄激素生成与其给药方式无关。结果还表明,睾丸环境中氧化状态的变化对于Pyralene诱导的雄激素生成抑制并不关键。