Mammalian Toxicology Department, Central Agricultural Pesticides Laboratory, Agricultural Research Center, Giza, Egypt.
Biochemistry Division, Faculty of Science, Cairo University, Giza, Egypt.
Environ Toxicol. 2021 May;36(5):958-974. doi: 10.1002/tox.23097. Epub 2021 Jan 4.
Gestational exposure to environmental pollutants can induce oxidative injury and apoptosis since the fetal organs are sensitively vulnerable to these chemicals. In this work, we have investigated the renal anti-apoptotic efficiency of linseed (LS) against the oxidative stress-mediated upregulation of the fetal apoptosis-related genes following the prenatal intoxication with diesel nanoparticles (DNPs) and/or fenitrothion (FNT). A fifty-six timed-pregnant rats were equally divided to eight groups; control, LS (20% in diet), DNPs (0.5 mg/kg by intratracheal inoculation), FNT (3.76 mg/kg by gavage), DNPs+FNT, LS + DNPs, LS + FNT, and LS + DNPs+FNT. The transmission electron microscope analysis revealed the spherical shape of diesel particles with a homogeneous nanosized range (20-92.3 nm) and the crystallinity was confirmed by electron diffraction microscopy. Administration of DNPs and/or FNT significantly increased fetal renal malondialdehyde, nitric oxide, and glutathione reductase as compared with the control group. However, they declined the level of glutathione together with the activities of glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, and catalase. Furthermore, DNPs and/or FNT elicited many histopathological changes in fetal renal cells, markedly up-regulated apoptosis-related gene expressions (p53, p21 caspase-3, and caspase-9), and evoked DNA breaks as detected by comet assay. Interestingly, LS supplementation significantly ameliorated the disturbances in oxidant/antioxidant biomarkers, downregulated the apoptosis gene expressions, and alleviated DNA damage alongside renal cell architecture. These findings reveal that the antioxidant and anti-apoptotic characteristics of LS are acceptable defender pointers for the renal injury especially during gestational exposure to DNPs and/or FNT.
胚胎期暴露于环境污染物会引起氧化损伤和细胞凋亡，因为胎儿器官对这些化学物质非常敏感。在这项工作中，我们研究了亚麻籽油（LS）对胎儿凋亡相关基因的抗凋亡作用，这些基因在产前吸入柴油纳米颗粒（DNPs）和/或fenitrothion（FNT）引起氧化应激后会上调。56 只妊娠大鼠被平均分为 8 组：对照组、LS（饮食中 20%）、DNPs（气管内接种 0.5mg/kg）、FNT（灌胃 3.76mg/kg）、DNPs+FNT、LS+DNPs、LS+FNT 和 LS+DNPs+FNT。透射电子显微镜分析显示，柴油颗粒呈球形，具有均匀的纳米尺寸范围（20-92.3nm），电子衍射显微镜证实了其结晶度。与对照组相比，DNPs 和/或 FNT 的给药显著增加了胎儿肾脏丙二醛、一氧化氮和谷胱甘肽还原酶的水平。然而，它们降低了谷胱甘肽的水平，同时降低了谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶、超氧化物歧化酶和过氧化氢酶的活性。此外，DNPs 和/或 FNT 在胎儿肾细胞中引起许多组织病理学变化，明显上调了凋亡相关基因的表达（p53、p21 caspase-3 和 caspase-9），并通过彗星试验检测到 DNA 断裂。有趣的是，LS 补充显著改善了氧化应激/抗氧化生物标志物的紊乱，下调了凋亡基因的表达，并缓解了 DNA 损伤以及肾细胞结构。这些发现表明，LS 的抗氧化和抗凋亡特性是一种可接受的防御指标，特别是在胚胎期暴露于 DNPs 和/或 FNT 期间，可以保护肾脏免受损伤。
