Galangin attenuates chlorpyrifos-induced kidney injury by mitigating oxidative stress and inflammation and upregulating Nrf2 and farnesoid-X-receptor in rats

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES Environmental toxicology and pharmacology Pub Date : 2024-08-22 DOI:10.1016/j.etap.2024.104542

Reem S. Alruhaimi , Ahmad F. Ahmeda , Omnia E. Hussein , Mohammed F. Alotaibi , Mousa O. Germoush , Hassan A. Elgebaly , Emad H.M. Hassanein , Ayman M. Mahmoud

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Abstract

Chlorpyrifos (CPF) is a highly toxic commonly used pesticide and can seriously harm human health. This study assessed the potential of galangin (GAL), an antioxidant flavonoid, to attenuate oxidative stress, inflammation and kidney injury caused by CPF, emphasizing the role of farnesoid-x-receptor (FXR) and Nrf2. Rats were supplemented with CPF and GAL for 28 days. CPF increased serum creatinine, urea and Kim-1, provoked several tissue alterations, and increased kidney ROS, malondialdehyde (MDA), NF-κB p65, TNF-α, iNOS, and caspase-3. GAL effectively ameliorated serum kidney injury markers, ROS, MDA, and TNF-α, suppressed NF-κB p65, iNOS, and caspase-3, and enhanced antioxidants. GAL suppressed Keap1 and upregulated FXR, Nrf2, HO-1 and NQO-1 in CPF-administered rats. GAL exhibited binding affinity with Keap1, FXR, caspase-3, iNOS, HO-1, and NF-κB. In conclusion, GAL is effective in preventing CPF nephrotoxicity by attenuating oxidative stress and inflammation. This protection is linked to upregulation of antioxidants, Nrf2/HO-1 signaling and FXR.

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高良姜素通过减轻氧化应激和炎症以及上调 Nrf2 和 Farnesoid-X 受体，减轻毒死蜱诱发的大鼠肾损伤。

毒死蜱（CPF）是一种剧毒的常用杀虫剂，会严重危害人类健康。本研究评估了一种抗氧化类黄酮--高良姜素（GAL）减轻毒死蜱引起的氧化应激、炎症和肾损伤的潜力，并强调了法尼类黄酮-x 受体（FXR）和 Nrf2 的作用。大鼠连续 28 天服用氯化石蜡和 GAL。CPF 增加了血清肌酐、尿素和 Kim-1，引起了多种组织改变，并增加了肾脏 ROS、丙二醛 (MDA)、NF-κB p65、TNF-α、iNOS 和 caspase-3。GAL 能有效改善血清肾损伤指标、ROS、MDA 和 TNF-α，抑制 NF-κB p65、iNOS 和 caspase-3，并增强抗氧化能力。在服用氯化石蜡的大鼠体内，GAL抑制Keap1，上调FXR、Nrf2、HO-1和NQO-1。GAL 与 Keap1、FXR、caspase-3、iNOS、HO-1 和 NF-κB 具有亲和力。总之，GAL 可通过减轻氧化应激和炎症来有效预防 CPF 肾毒性。这种保护作用与抗氧化剂、Nrf2/HO-1 信号转导和 FXR 的上调有关。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.