普罗布考在百草枯中毒致肺损伤中的保护作用

doi:10.3760/cma.j.issn.1007-1245.2023.07.006

摘要/Abstract

摘要：

百草枯中毒可导致多种器官的损伤，其对肾脏、心脏、肝脏、消化道和中枢神经系统等许多器官都有不良影响，其中尤以肺部损伤最为常见。治疗方法主要包括催吐、洗胃、导泻、抗氧化、免疫调节、血液灌流等，但由于百草枯中毒缺乏特效解毒剂，目前病死率仍居高不下。普罗布考是一种酚类降脂剂，具有抗氧化、抗炎及抗纤维化特性，已广泛应用于心血管疾病的临床治疗和预防。近年来研究发现，普罗布考可减轻药物诱导产生的氧化应激反应及肺纤维化。本文就普罗布考在百草枯中毒所致肺损伤中的保护意义进行综述。

关键词:

百草枯, 普罗布考, 氧化应激, 炎症反应, 肺损伤

Abstract:

Paraquat can lead to injury of multiple organs, it can induce a range of adverse effects on various organs, such as the kidneys, heart, liver, gastrointestinal tract, and nervous system. Among them, lung injury is the most common. The current clinical treatment includes emetics, gastric lavage, catharsis, anti-oxidant therapy, immunoregulation, hemoperfusion, et al. The lack of effective antidotes is the significant cause of high mortality in paraquat poisoning. Probucol is a phenolic lipid-lowering agent with antioxidant, anti-inflammatory, and antifibrotic effects, which has been widely used in the clinical treatment and prevention of cardiovascular diseases. Recent studies have discovered that probucol can ameliorate the oxidative stress response and pulmonary fibrosis caused by drugs. The protective significance of probucol in lung injury induced by paraquat poisoning is reviewed in this paper.

Key words:

Paraquat, Probucol, Oxidative stress, Inflammatory response, Lung injury

徐菡李文鹏张骁慧张金英.

普罗布考在百草枯中毒致肺损伤中的保护作用 [J]. 国际医药卫生导报, 2023, 29(7): 913-916.

Xu Han, Li Wenpeng, Zhang Xiaohui, Zhang Jinying.

Protective effect of probucol in lung injury induced by paraquat poisoning [J]. International Medicine and Health Guidance News, 2023, 29(7): 913-916.

参考文献

[1] 中国医师协会急诊医师分会.急性百草枯中毒诊治专家共识(2013)[J].中国急救医学,2013,33(6):484-489. DOI:10.3969/j.issn.1002-1949.2013.6.002.
[2] 段琬钰,樊卓,张文迪,等.我国2008-2018年急性百草枯中毒患者的流行病学分析[J].河北医科大学学报,2022,43(1):80-83. DOI:10.3969/j.issn.1007-3205.2022.01.017.
[3] Yang R, Hu Z, Zhang P, et al. Probucol ameliorates hepatic stellate cell activation and autophagy is associated with farnesoid X receptor[J]. J Pharmacol Sci, 2019, 139(2):120-128. DOI: 10.1016/j.jphs.2018.12.005.
[4] Senoner T, Dichtl W. Oxidative stress in cardiovascular diseases: still a therapeutic target? [J]. Nutrients, 2019, 11(9):2090. DOI: 10.3390/nu11092090.
[5] 王瑜,喻安永,李建国,等.Nrf2-ARE信号通路在百草枯中毒中的研究进展[J].东南大学学报(医学版),2017,36(5):868-871. DOI:10.3969/j.issn.1671-6264.2017.05.038.
[6] Shukla S, Singh D, Kumar V, et al. NADPH oxidase mediated maneb- and paraquat-induced oxidative stress in rat polymorphs: crosstalk with mitochondrial dysfunction[J]. Pestic Biochem Physiol, 2015, 123:74-86. DOI: 10.1016/j.pestbp.2015.03.007.
[7] Liu MW, Su MX, Tang DY, et al. Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression[J]. BMC Pulm Med, 2019, 19(1):35. DOI: 10.1186/s12890-019-0799-5.
[8] Jiang F, Li S, Jiang Y, et al. Fluorofenidone attenuates paraquat‑induced pulmonary fibrosis by regulating the PI3K/Akt/mTOR signaling pathway and autophagy[J]. Mol Med Rep, 2021, 23(6):405. DOI: 10.3892/mmr.2021.12044.
[9] Han G, Zhang Y, Li H. The combination treatment of curcumin and probucol protects chondrocytes from TNF-α induced inflammation by enhancing autophagy and reducing apoptosis via the PI3K-Akt-mTOR pathway[J]. Oxid Med Cell Longev, 2021, 2021:5558066. DOI: 10.1155/2021/5558066.
[10] 肖雪娟,尹崴仪,朱妍妮,等.百草枯慢性暴露对大鼠血清白介素-6、转化生长因子-β浓度的影响[J].职业与健康,2021,37(23):3190-3192,3196. DOI:10.13329/j.cnki.zyyjk.2021.0733.
[11] Zhou SX, Zhou Y, Zhang YL, et al. Antioxidant probucol attenuates myocardial oxidative stress and collagen expressions in post-myocardial infarction rats[J]. J Cardiovasc Pharmacol, 2009, 54(2):154-162. DOI: 10.1097/FJC.0b013e3181af6d7f.
[12] Mei X, Zeng J, Liu DF, et al. Abnormalities of the PRMT1-ADMA-DDAH1 metabolism axis and probucol treatment in diabetic patients and diabetic rats[J]. Ann Palliat Med, 2021, 10(3):3343-3353. DOI: 10.21037/apm-21-417.
[13] Singla DK, Kaur K, Sharma AK, et al. Probucol promotes endogenous antioxidant reserve and confers protection against reperfusion injury[J]. Can J Physiol Pharmacol, 2007, 85(3-4):439-443. DOI: 10.1139/y06-071.
[14] 王永玲,郑晶,张晓峰.百草枯诱导帕金森病小鼠行为学和病理学变化的动态观察[J].现代预防医学,2020,47(22):4160-4163,4167.
[15] Ray A, Martinez BA, Berkowitz LA, et al. Mitochondrial dysfunction, oxidative stress, and neurodegeneration elicited by a bacterial metabolite in a C. elegans Parkinson's model[J]. Cell Death Dis, 2014, 5(1):e984. DOI: 10.1038/cddis.2013.513.
[16] Lau M, Giri K, Garcia-Bennett AE. Antioxidant properties of probucol released from mesoporous silica[J]. Eur J Pharm Sci, 2019, 138:105038. DOI: 10.1016/j.ejps.2019.105038.
[17] Tsukamoto M, Tampo Y, Sawada M, et al. Paraquat-induced membrane dysfunction in pulmonary microvascular endothelial cells[J]. Pharmacol Toxicol, 2000, 86(3):102-109. DOI: 10.1034/j.1600-0773.2000.d01-19.x.
[18] Gawarammana IB, Buckley NA. Medical management of paraquat ingestion[J]. Br J Clin Pharmacol, 2011, 72(5):745-757. DOI: 10.1111/j.1365-2125.2011.04026.x.
[19] Ortega-Arellano HF, Jimenez-Del-Rio M, Velez-Pardo C. Neuroprotective effects of methanolic extract of avocado persea americana (var. Colinred) peel on paraquat-induced locomotor impairment, lipid peroxidation and shortage of life span in transgenic knockdown parkin drosophila melanogaster[J]. Neurochem Res, 2019, 44(8):1986-1998. DOI: 10.1007/s11064-019-02835-z.
[20] Charão MF, Goethel G, Brucker N, et al. Melatonin-loaded lipid-core nanocapsules protect against lipid peroxidation caused by paraquat through increased SOD expression in Caenorhabditis elegans[J]. BMC Pharmacol Toxicol, 2019, 20(Suppl 1):80. DOI: 10.1186/s40360-019-0352-4.
[21] Medzhitov R. Origin and physiological roles of inflammation[J]. Nature, 2008, 454(7203):428-435. DOI: 10.1038/nature07201.
[22] Sun Y, Zheng J, Xu Y, et al. Paraquat-induced inflammatory response of microglia through HSP60/TLR4 signaling[J]. Hum Exp Toxicol, 2018, 37(11):1161-1168. DOI: 10.1177/0960327118758152.
[23] Amin F, Memarzia A, Kazemi Rad H, et al. Systemic inflammation and oxidative stress induced by inhaled paraquat in rat improved by carvacrol, possible role of PPARγ receptors[J]. Biofactors, 2021, 47(5):778-787. DOI: 10.1002/biof.1761.
[24] Liu Z, Wang X, Li L, et al. Hydrogen sulfide protects against paraquat-induced acute liver injury in rats by regulating oxidative stress, mitochondrial function, and inflammation[J]. Oxid Med Cell Longev, 2020, 2020:6325378. DOI: 10.1155/2020/6325378.
[25] Amin F, Memarzia A, Roohbakhsh A, et al. Zataria multiflora and pioglitazone affect systemic inflammation and oxidative stress induced by inhaled paraquat in rats[J]. Mediators Inflamm, 2021, 2021:5575059. DOI: 10.1155/2021/5575059.
[26] Amin F, Roohbakhsh A, Memarzia A, et al. Immediate and late systemic and lung effects of inhaled paraquat in rats[J]. J Hazard Mater, 2021, 415:125633. DOI: 10.1016/j.jhazmat.2021.125633.
[27] Wu Z, Wang X, Jiang X. Study on the mechanism of probucol nanosuspension on hyperlipidemic pancreatitis and regulation of blood lipid function[J]. J Nanosci Nanotechnol, 2021, 21(2):1286-1292. DOI: 10.1166/jnn.2021.18663.
[28] Sun H, Jiang Y, Song Y, et al. The MUC5B mucin is involved in paraquat-induced lung inflammation[J]. Oxid Med Cell Longev, 2020, 2020:7028947. DOI: 10.1155/2020/7028947.
[29] Li Y, Zhao Q, Cao Y, et al. Probucol decreases homocysteine-stimulated CRP production in rat aortic smooth muscle cells via regulating HO-1/NADPH oxidase/ROS/p38 pathway[J]. Acta Biochim Biophys Sin (Shanghai), 2021, 53(2):212-219. DOI: 10.1093/abbs/gmaa163.
[30] Tanous D, Hime N, Stocker R. Anti-atherosclerotic and anti-diabetic properties of probucol and related compounds[J]. Redox Rep, 2008, 13(2):48-59. DOI: 10.1179/135100008X259196.
[31] Mooranian A, Ionescu CM, Wagle SR, et al. Probucol pharmacological and bio-nanotechnological effects on surgically transplanted graft due to powerful anti-inflammatory, anti-fibrotic and potential bile acid modulatory actions[J]. Pharmaceutics, 2021, 13(8):1304. DOI: 10.3390/pharmaceutics13081304.
[32] Jian X, Li M, Zhang Y, et al. Role of growth factors in acute lung injury induced by paraquat in a rat model[J]. Hum Exp Toxicol, 2011, 30(6):460-469. DOI: 10.1177/0960327110372648.
[33] Sun Z, Yang Z, Wang M, et al. Paraquat induces pulmonary fibrosis through Wnt/β-catenin signaling pathway and myofibroblast differentiation[J]. Toxicol Lett, 2020, 333:170-183. DOI: 10.1016/j.toxlet.2020.08.004.
[34] Liu MW, Liu R, Wu HY, et al. Radix puerariae extracts ameliorate paraquat-induced pulmonary fibrosis by attenuating follistatin-like 1 and nuclear factor erythroid 2p45-related factor-2 signalling pathways through downregulation of miRNA-21 expression[J]. BMC Complement Altern Med, 2016, 16:11. DOI: 10.1186/s12906-016-0991-6.
[35] Ma J, Zhao S, Gao G, et al. Probucol protects against asymmetric dimethylarginine-induced apoptosis in the cultured human brain microvascular endothelial cells[J]. J Mol Neurosci, 2015, 57(4):546-553. DOI: 10.1007/s12031-015-0635-1.
[36] Zhu Y, Tan J, Xie H, et al. HIF-1α regulates EMT via the Snail and β-catenin pathways in paraquat poisoning-induced early pulmonary fibrosis[J]. J Cell Mol Med, 2016, 20(4):688-697. DOI: 10.1111/jcmm.12769.
[37] Zhang HX, Li YN, Wang XL, et al. Probucol ameliorates EMT and lung fibrosis through restoration of SIRT3 expression[J]. Pulm Pharmacol Ther, 2019, 57:101803. DOI: 10.1016/j.pupt.2019.101803.
[38] Pourgholamhossein F, Rasooli R, Pournamdari M, et al. Pirfenidone protects against paraquat-induced lung injury and fibrosis in mice by modulation of inflammation, oxidative stress, and gene expression[J]. Food Chem Toxicol, 2018, 112:39-46. DOI: 10.1016/j.fct.2017.12.034.
[39] Su X, Wang Y, Zhou G, et al. Probucol attenuates ethanol-induced liver fibrosis in rats by inhibiting oxidative stress, extracellular matrix protein accumulation and cytokine production[J]. Clin Exp Pharmacol Physiol, 2014, 41(1):73-80. DOI: 10.1111/1440-1681.12182.
[40] Matsuzawa Y, Kawashima T, Yamazaki R, et al. Inhibitory effects of clinical reagents having anti-oxidative activity on transforming growth factor-β1-induced expression of α-smooth muscle actin in human fetal lung fibroblasts[J]. J Toxicol Sci, 2011, 36(6):733-740. DOI: 10.2131/jts.36.733.
[41] Liu K, Zhan Z, Gao W, et al. Cyclosporine attenuates Paraquat-induced mitophagy and pulmonary fibrosis[J]. Immunopharmacol Immunotoxicol, 2020, 42(2):138-146. DOI: 10.1080/08923973.2020.1729176.
[42] Nakamura R, Egashira K, Machida Y, et al. Probucol attenuates left ventricular dysfunction and remodeling in tachycardia-induced heart failure: roles of oxidative stress and inflammation[J]. Circulation, 2002, 106(3):362-367. DOI: 10.1161/01.cir.0000021430.04195.51.