Abdulaal Wesam H, Mohammed Nourelhuda A, Taher Ehab S, Awan Zuhier A, Zeyadi Mustafa Adnan, Ibrahim Tarek S, Ali Fares E M, Hassanein Emad H M
Department of Biochemistry, Faculty of Science, Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Physiology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
J Biochem Mol Toxicol. 2025 Sep;39(9):e70467. doi: 10.1002/jbt.70467.
Chlorpyrifos (CPF) is a pesticide commonly used for pest management. Regretfully, there is evidence that pesticides can cause pulmonary toxicity. The phytochemical umbelliferone (UMB) possesses anti-inflammatory and antioxidant bioactivities. This investigation aimed to determine whether UMB protects against pulmonary toxicity induced by CPF. Rats were divided into four groups: group I (control), group II (30 mg/kg of UMB), group III (10 mg/kg of untreated CPF), and group IV (30 mg/kg of CPF + UMB). Interestingly, UMB reduced pulmonary intoxication, as evidenced by the attenuation of CPF-induced histopathological alterations and the lowering of ALP, LDH, and CRP levels. Furthermore, UMB decreased CPF-induced pulmonary oxidative damage by reducing malondialdehyde (MDA) content and increasing GSH and SOD levels, which was mediated by the upregulation of Nrf2, HO-1, PPAR-γ, and cytoglobin expression. UMB decreased CPF-induced lung inflammation by lowering MPO, TNF-α, and IL-1β levels, as well as NF-κB expression. Additionally, UMB counteracted lung necroptosis by downregulating RIPK-1, RIPK3, mixed-lineage kinase domain-like pseudokinase (MLKL), and Caspase-8, as confirmed by in silico studies. Accordingly, UMB could be a sound therapeutic strategy for mitigating CPF-induced lung intoxication, as it balances antioxidants and oxidants, reduces cellular inflammation, and prevents lung tissue necroptosis.
毒死蜱（CPF）是一种常用于害虫防治的杀虫剂。遗憾的是，有证据表明杀虫剂会导致肺部毒性。植物化学物质伞形花内酯（UMB）具有抗炎和抗氧化生物活性。本研究旨在确定UMB是否能预防CPF诱导的肺部毒性。将大鼠分为四组：第一组（对照组）、第二组（30毫克/千克UMB）、第三组（10毫克/千克未处理的CPF）和第四组（30毫克/千克CPF + UMB）。有趣的是，UMB减轻了肺部中毒，CPF诱导的组织病理学改变减轻以及碱性磷酸酶（ALP）、乳酸脱氢酶（LDH）和C反应蛋白（CRP）水平降低证明了这一点。此外，UMB通过降低丙二醛（MDA）含量并增加谷胱甘肽（GSH）和超氧化物歧化酶（SOD）水平，减少了CPF诱导的肺部氧化损伤，这是由核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）、过氧化物酶体增殖物激活受体-γ（PPAR-γ）和细胞珠蛋白表达上调介导的。UMB通过降低髓过氧化物酶（MPO）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平以及核因子κB（NF-κB）表达，减轻了CPF诱导的肺部炎症。此外，计算机模拟研究证实，UMB通过下调受体相互作用蛋白激酶-1（RIPK-1）、RIPK3、混合谱系激酶结构域样假激酶（MLKL）和半胱天冬酶-8（Caspase-8）来对抗肺部坏死性凋亡。因此，UMB可能是减轻CPF诱导的肺部中毒的一种合理治疗策略，因为它平衡了抗氧化剂和氧化剂，减少了细胞炎症，并防止了肺组织坏死性凋亡。
