University of Navarra, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, c/Irunlarrea 1, 31008 Pamplona, Spain.
University of Navarra, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, c/Irunlarrea 1, 31008 Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Spain.
Food Chem Toxicol. 2018 Jun;116(Pt B):379-387. doi: 10.1016/j.fct.2018.04.050. Epub 2018 Apr 22.
Ochratoxin A (OTA) is a mycotoxin considered the most powerful renal carcinogen in rodents and classified as a possible human carcinogen. Though its mechanism of action is still unknown, indirect DNA reactivity mediated by oxidative stress has been hypothesized to play an important role. Moreover, large sex-differences have been observed in carcinogenicity studies, male rats being more sensitive than females. Male and female F344 rats were administered (p.o.) with bicarbonate or 0.5 mg OTA/kg b.w. for 7 days; or with bicarbonate, 0.21 or 0.5 mg OTA/kg b.w. for 21 days. Total glutathione (tGSH) and oxidized glutathione (GSSG) levels, glutathione S-transferase (GST) and superoxide dismutase (SOD) activities were analysed in kidneys. The standard alkaline comet assay was used in combination with Formamidopyrimidine-DNA glycosylase (Fpg) to detect oxidized DNA bases in kidney. No biologically relevant sex-differences were observed in all the oxidative-stress related parameters analysed. Indeed, no relevant oxidative-stress related response was observed between treated animals and controls. In accordance with the similar OTA levels and histopathological changes between both sexes observed previously in the same animals, and with other oxidative-stress related parameters measured by others, results support that there are no differences between sexes in the oxidative stress response to OTA.
赭曲霉毒素 A（OTA）是一种真菌毒素，被认为是啮齿动物中最强大的肾致癌物，被归类为可能的人类致癌物。尽管其作用机制尚不清楚，但已假设氧化应激介导的间接 DNA 反应可能发挥重要作用。此外，在致癌性研究中观察到了很大的性别差异，雄性大鼠比雌性大鼠更敏感。雄性和雌性 F344 大鼠经口给予碳酸氢盐或 0.5mg OTA/kg bw 连续 7 天；或给予碳酸氢盐、0.21 或 0.5mg OTA/kg bw 连续 21 天。分析肾脏中的总谷胱甘肽（tGSH）和氧化型谷胱甘肽（GSSG）水平、谷胱甘肽 S-转移酶（GST）和超氧化物歧化酶（SOD）活性。使用碱性彗星试验联合 Formamidopyrimidine-DNA glycosylase（Fpg）检测肾脏中氧化的 DNA 碱基。在所有分析的氧化应激相关参数中，均未观察到具有生物学意义的性别差异。事实上，在处理动物和对照组之间未观察到与氧化应激相关的任何相关反应。与之前在同一批动物中观察到的两性之间相似的 OTA 水平和组织病理学变化以及其他人测量的其他氧化应激相关参数一致，结果表明两性对 OTA 引起的氧化应激反应没有差异。
