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姜黄素和纳米姜黄素对大鼠磷化铝诱导的亚急性肺损伤的保护作用评估:通过SIRT1/FOXO3信号通路调节氧化应激

Evaluation of Protective Effects of Curcumin and Nanocurcumin on Aluminium Phosphide‑Induced Subacute Lung Injury in Rats: Modulation of Oxidative Stress through SIRT1/FOXO3 Signalling Pathway.

作者信息

Mahlooji Mohammad Ali, Heshmati Ali, Kheiripour Nejat, Ghasemi Hassan, Asl Sara Soleimani, Solgi Ghasem, Ranjbar Akram, Hosseini Asieh

机构信息

Department of Pharmacology and Toxicology, School of Pharmacy, Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Nutrition Health Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Drug Res (Stuttg). 2022 Feb;72(2):100-108. doi: 10.1055/a-1647-2418. Epub 2021 Oct 6.

Abstract

OBJECTIVE

Aluminum phosphide (AlP) is widely used to protect stored food products and grains from pests and rodents. The availability of AlP, especially in Asian countries it has become a desirable factor to commit suicide. The phosphine produced from ALP is a very reactive radical and a respiratory inhibitor that causes oxidative damage. There is no dedicated antidote or effective drug to manage AlP-induced lung toxicity. The present study aims to evaluate and compare the protective effects of curcumin and nanocurcumin on ALP‑induced subacute lung injury and determine the underlying mechanism.

METHODS

Rats were exposed to AlP (2 mg/kg/day, orally)+curcumin or nanocurcumin (100 mg/kg/day, orally) for 7 days. Then rats were anesthetized and lung tissues were collected. Oxidative stress biomarkers, genes expression of antioxidant enzymes, participated genes in the SIRT1/FOXO3 pathway, and lung histopathology were assessed by biochemical and ELISA methods, Real-Time PCR analysis, and H&E staining.

RESULTS

Curcumin and nanocurcumin produced a remarkable improvement in AlP-induced lung damage through reduction of MDA, induction of antioxidant capacity (TAC, TTG) and antioxidant enzymes (CAT, GPx), modulation of histopathological changes, and up-regulation of genes expression of SIRT1, FOXO3, FOXO1 in lung tissue.

CONCLUSION

Nanocurcumin had a significantly more protective effect than curcumin to prevent AlP-induced lung injury via inhibition of oxidative stress. Nanocurcumin could be considered a suitable therapeutic choice for AlP poisoning.

摘要

目的

磷化铝(AlP)被广泛用于保护储存的食品和谷物免受害虫和啮齿动物侵害。在亚洲国家,AlP的可得性已成为自杀的一个诱发因素。AlP产生的磷化氢是一种极具反应性的自由基和呼吸抑制剂,会导致氧化损伤。目前尚无专门的解毒剂或有效药物来治疗AlP引起的肺毒性。本研究旨在评估和比较姜黄素和纳米姜黄素对AlP诱导的亚急性肺损伤的保护作用,并确定其潜在机制。

方法

将大鼠暴露于AlP(2毫克/千克/天,口服)+姜黄素或纳米姜黄素(100毫克/千克/天,口服)7天。然后将大鼠麻醉并收集肺组织。通过生化和酶联免疫吸附测定法、实时聚合酶链反应分析和苏木精-伊红染色评估氧化应激生物标志物、抗氧化酶的基因表达、参与SIRT1/FOXO3途径的基因以及肺组织病理学。

结果

姜黄素和纳米姜黄素通过降低丙二醛、诱导抗氧化能力(总抗氧化能力、总硫醇)和抗氧化酶(过氧化氢酶、谷胱甘肽过氧化物酶)、调节组织病理学变化以及上调肺组织中SIRT1、FOXO3、FOXO1的基因表达,显著改善了AlP诱导的肺损伤。

结论

纳米姜黄素通过抑制氧化应激对预防AlP诱导的肺损伤具有比姜黄素更显著的保护作用。纳米姜黄素可被视为AlP中毒的合适治疗选择。

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