Mufti Afoua, Jalouli Maroua, Nahdi Saber, Tlili Nizar, Alqahtani Wadha, Mansour Lamjed, Alwasel Saleh, Harrath Abdel Halim
Laboratory of Biotechnology and Biomonitoring of the Environment and Oasis Ecosystems, Faculty of Sciences of Gafsa, Gafsa 2112, Tunisia.
Department of Biology, College of Sciences, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
Biology (Basel). 2023 Jan 20;12(2):162. doi: 10.3390/biology12020162.
This study examined how maternal exposure to acephate-an organophosphate-based insecticide-affected the renal development in rat offspring during adulthood. Virgin female Wistar rats were randomly allocated to three groups: group 1 (control) received sterile water; groups 2 and 3 were intragastrically exposed to low (14 mg/kg) and high (28 mg/kg) doses of acephate from day 6 of pregnancy until delivery, respectively. Further, the offspring of the adult female rats were euthanized in postnatal week 8. Compared with the controls, the adult rat offspring with exposure to low and high doses of acephate exhibited elevated plasma creatinine and blood urea nitrogen levels. Additionally, immunofluorescence analysis revealed the upregulation of autophagic marker genes ( and ) in the acephate-treated rat offspring, thereby suggesting the induction of an autophagic mechanism. Notably, the increased malondialdehyde level, decreased glutathione level, and decreased superoxide dismutase and catalase activities confirmed the ability of acephate to induce oxidative stress and apoptosis in the kidneys of the rat offspring. This may explain the renal histopathological injury detected using hematoxylin and eosin staining. Furthermore, a reverse transcription polymerase chain reaction revealed that the mRNA expression levels of the Na/K-ATPase and the epithelial sodium channel (ENaC) genes were significantly higher in the kidney of female offspring than that of controls owing to acephate toxicity. However, there was no significant effect of acephate on the expression of in the treatment group compared with the control group. Overall, the present findings suggest that oxidative stress caused by prenatal exposure to acephate causes nephrotoxicity and histopathological alterations in adult rat offspring, likely by actions on renal ENaC and Na/K-ATPase genes as well as the autophagic markers and .
本研究考察了母体暴露于乙酰甲胺磷（一种有机磷类杀虫剂）如何影响成年大鼠后代的肾脏发育。将未交配的雌性Wistar大鼠随机分为三组：第1组（对照组）给予无菌水；第2组和第3组分别在妊娠第6天至分娩期间经口灌胃低剂量（14 mg/kg）和高剂量（28 mg/kg）的乙酰甲胺磷。此外，成年雌性大鼠的后代在出生后第8周实施安乐死。与对照组相比，暴露于低剂量和高剂量乙酰甲胺磷的成年大鼠后代血浆肌酐和血尿素氮水平升高。此外，免疫荧光分析显示，经乙酰甲胺磷处理的大鼠后代中自噬标记基因（和）上调，从而提示自噬机制被诱导。值得注意的是，丙二醛水平升高、谷胱甘肽水平降低以及超氧化物歧化酶和过氧化氢酶活性降低证实了乙酰甲胺磷能够在大鼠后代肾脏中诱导氧化应激和细胞凋亡。这可能解释了苏木精-伊红染色检测到的肾脏组织病理学损伤。此外，逆转录聚合酶链反应显示，由于乙酰甲胺磷毒性，雌性后代肾脏中Na/K-ATP酶和上皮钠通道（ENaC）基因的mRNA表达水平显著高于对照组。然而，与对照组相比，乙酰甲胺磷对治疗组中 的表达没有显著影响。总体而言，目前的研究结果表明，产前暴露于乙酰甲胺磷所导致的氧化应激会引起成年大鼠后代的肾毒性和组织病理学改变，可能是通过作用于肾脏ENaC和Na/K-ATP酶基因以及自噬标记物和 来实现的。
