Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia.
Department of Zoology, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
Toxins (Basel). 2023 Nov 17;15(11):663. doi: 10.3390/toxins15110663.
Fumonisin B1 (FB1), a mycotoxin produced by , is one of the most common pollutants in natural foods and agricultural crops. It can cause chronic and severe health issues in humans and animals. The aim of this study was to evaluate the transgenerational effects of FB1 exposure on the structure and function of the kidneys in offspring. Virgin female Wistar rats were randomly divided into three groups: group one (control) received sterile water, and groups two and three were intragastrically administered low (20 mg/kg) and high (50 mg/kg) doses of FB1, respectively, from day 6 of pregnancy until delivery. Our results showed that exposure to either dose of FB1 caused histopathological changes, such as atrophy, hypercellularity, hemorrhage, calcification, and a decrease in the glomerular diameter, in both the first and second generations. The levels of the antioxidant markers glutathione, glutathione S-transferase, and catalase significantly decreased, while malondialdehyde levels increased. Moreover, autophagy was induced, as immunofluorescence analysis revealed that LC-3 protein expression was significantly increased in both generations after exposure to either dose of FB1. However, a significant decrease in methyltransferase (DNMT3) protein expression was observed in the first generation in both treatment groups (20 mg/kg and 50 mg/kg), indicating a decrease in DNA methylation as a result of early-life exposure to FB1. Interestingly, global hypomethylation was also observed in the second generation in both treatment groups despite the fact that the mothers of these rats were not exposed to FB1. Thus, early-life exposure to FB1 induced nephrotoxicity in offspring of the first and second generations. The mechanisms of action underlying this transgenerational effect may include oxidative stress, autophagy, and DNA hypomethylation.
黄曲霉毒素 B1（FB1）是一种由真菌产生的毒素，是天然食品和农作物中最常见的污染物之一。它会导致人类和动物慢性和严重的健康问题。本研究旨在评估 FB1 暴露对子代肾脏结构和功能的跨代影响。雌性 Wistar 大鼠被随机分为三组：一组（对照组）给予无菌水，二组和三组分别经口给予低（20mg/kg）和高（50mg/kg）剂量 FB1，从妊娠第 6 天至分娩。结果显示，两种剂量的 FB1 暴露均导致了第一和第二代的组织病理学变化，如萎缩、细胞增生、出血、钙化和肾小球直径减小。抗氧化标志物谷胱甘肽、谷胱甘肽 S-转移酶和过氧化氢酶的水平显著降低，而丙二醛水平升高。此外，自噬被诱导，免疫荧光分析显示，两种剂量的 FB1 暴露后，LC-3 蛋白表达在两代中均显著增加。然而，在两个处理组（20mg/kg 和 50mg/kg）中，第一代的甲基转移酶（DNMT3）蛋白表达显著降低，表明早期暴露于 FB1 导致 DNA 甲基化减少。有趣的是，尽管这些大鼠的母亲没有接触 FB1，但在两个处理组中，第二代也观察到了全基因组低甲基化。因此，早期暴露于 FB1 会导致第一代和第二代后代的肾脏毒性。这种跨代效应的作用机制可能包括氧化应激、自噬和 DNA 低甲基化。
