Metabolism Analysis

Rat mitochondrial dysfunction induced by 4-(3-methoxy-4-hydroxybenzaliminyl) phenyl arsenic oxide*

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  • 1. College of Chemistry and Chemical Engineering, Hubei Polytechnic University, Huangshi 435003, China;
    2. Hubei Key Laboratory of Mine Environmental Pollution Control & Remediation, Huangshi 435003, China;
    3. Medical Record Statistics Department, Huangshi Center Hospital, Edong Healthcare Group, Huangshi 435002, China;
    4. Chibi Yonghua Second Pig breeding Farm Co., Ltd., Chibi 437300, China

Received date: 2023-04-22

  Online published: 2024-06-24

Abstract

Objective: To clarify the pharmacological and toxicological characteristics of arsenic based compounds, and to study the behavior and mechanism of 4- (3- methoxy group -4- hydroxybenzimidyl) phenyl arsenic oxide (MRO) affecting the structure and function of mitochondria in isolated Wistar rat liver mitochondria. Methods: The changes of absorbance of mitochondria at 540 nm in different buffers were monitored by ultraviolet-visible spectroscopy to study the effect of MRO on mitochondrial swelling and ion permeability. Using hematoporphyrin (HP) and Rhodamine 123 (Rh123) as fluorescent labeling probes, the effects of MRO on mitochondrial membrane fluidity and membrane potential were studied by fluorescence polarization and fluorescence photometry. The respiratory oxygen consumption rate of mitochondria was studied by oxygen electrode analysis, and the effect of MRO on the process of mitochondrial oxidative phosphorylation was studied. Results: MRO significantly damaged the outer mitochondrial membrane potential and ionic permeability, resulting in the development of mitochondrial membrane permeability transition pore, and finally caused mitochondrial swelling. At the same time, MRO inhibits mitochondrial oxidative phosphorylation and respiratory function through uncoupling effect. Conclusion: This study provides basic information for the comprehensive analysis of the biological activities of arsenic-based compounds, and also provides theoretical basis for the design and mechanism of action of arsenic-based anti-tumor drugs.

Cite this article

JIAO Yuan-hong, ZHANG Xiao-hui, XU Juan, PAN Ling-li, XIONG Shan . Rat mitochondrial dysfunction induced by 4-(3-methoxy-4-hydroxybenzaliminyl) phenyl arsenic oxide*[J]. Chinese Journal of Pharmaceutical Analysis, 2023 , 43(8) : 1352 -1359 . DOI: 10.16155/j.0254-1793.2023.08.11

References

[1] 刘宇, 李成, 朱卫, 等. NaAsO2通过Hippo通路影响PC12细胞形态和突触蛋白 [J].中国药理学通报, 2023, 39(2):399
LIU Y, LI C, ZHU W, et al. Sodium arsenite influences morphology and synap-tic proteins via Hippo pathway of PC12 cells [J].Chin Pharmacol Bull, 2023, 39(2):399
[2] ANUPAMA S, SUNIL K. Arsenic exposure with reference to neurological impairment: an overview [J].Rev Environ Health, 2019, 34(4):403
[3] ZHAO Q, PAN W, LI J, et al. Effects of neuron autophagy induced by arsenic and fluoride on spatial learning and memory in offspring rats [J].Chemosphere,2022, 308(2):136341
[4] 胡春, 辛迪薇, 彭志兵, 等. 食品中砷形态分析技术研究进展 [J].粮食科技与经济, 2022, 47(6):69
HU C, XIN DW, PENG ZB, et al. Research progress on arsenic morphological analysis in food [J].Grain Sci Technol Econ, 2022, 47(6):69
[5] MELGAR MJ, ALONSO J, GARCÍA MA. Total contents of arsenic and associated health risks in edible mushrooms, mushroom supplements and growth substrates from Galicia (NW Spain) [J].Food Chem Toxicol, 2014,73: 44
[6] DA SCA, OLIVEIRA SSD, BORGES GCA, et al. Metals and arsenic in marine fish commercialized in the NE Brazil: risk to human health [J].Human Ecol Risk Assess: an Int J, 2020, 26(3):695
[7] MILLER WH, SCHIPPER HM, LEE JS, et al. Mechanisms of action of arsenic trioxide [J].Cancer Res, 2002, 62(14):3893
[8] 张璇, 黄健, 王金辉, 等. 三氧化二砷结合靶向递送系统——实体瘤治疗的新策略 [J].中国现代中药, 2022, 24(9):1797
ZHANG X, HUANG J, WANG JH, et al. Arsenic trioxide combined with targeted delivery systems: new strategies for solid tumor therapy [J].Mod Chin Med, 2022, 24(9):1797
[9] ISLAM K, QIAN WQ, HAN JY, et al. Metabolism, toxicity and anticancer activities of arsenic compounds [J].Oncotarget, 2017, 8(14):23905
[10] 周倩, 尹锦瑶, 谭婧文, 等. 砷及其主要代谢产物对A549细胞凋亡及促凋亡基因Bad和Bik表达的影响 [J].中华劳动卫生职业病杂志, 2022, 40(9):661
ZHOU Q, YIN JY, TAN JW, et al. Effects of arsenic and its main metabolites on A549 cell apoptosis and the expression of pro-apoptotic genes Bad and Bik [J].Chin J Ind Hyg Occup Dis, 2022, 40(9):661
[11] 张斯琦, 刘丹丹, 孙美琪, 等. 肿瘤细胞能量代谢特点的研究进展 [J].吉林医药学院学报, 2023, 44(1):49
ZHANG SQ, LIU DD, SUN MQ, et al. Research progress on energy metabolism characteristics of tumor cells [J].J Jilin Med Univ, 2023, 44(1):49
[12] ZHAO Y, DONG Q, LI J, et al. Targeting cancer stem cells and their niche: perspectives for future therapeutic targets and strategies [J].Semin Cancer Biol, 2018, 53:139
[13] JIAO YH,ZHANG Q,PAN LL, et al. Rat liver mitochondrial dysfunction induced by an organic arsenical compound 4-(2-nitrobenzaliminyl) phenyl arsenoxide [J].J Membrane Biol, 2015, 248(6):191
[14] LI RF, SONG XW, GAO S, et al. Analysis on the interactions between the first introns and other introns in mitochondrial ribosomal protein genes [J].Front Microbiol, 2022, 13: 1091698
[15] QIU J, YANG TH, LONG YL, et al. Mitochondrial respiration inhibitor enhances the anti-tumor effect of high-dose ascorbic acid in castration-resistant prostate cancer [J].J Mol Med, 2022, 101(1-2):125
[16] PAOLO B, MICHELA C, GIOVANNA L. The mitochondrial permeability transition: recent progress and open questions [J].FEBS J, 2021, 289(22):7051
[17] YISANG Y, HAKJOO L, MARILEN F, et al. Non-conventional mitochondrial permeability transition: its regulation by mitochondrial dynamics [J].Biochim Biophys Acta Bioenerg, 2022, 1864(1):148914
[18] MASSIMO B, CARLOTTA G, PAOLO P. Molecular mechanisms and consequences of mitochondrial permeability transition [J].Nat Rev Mol Cell Biol, 2021, 23(4):266
[19] YANG YP, WANG WP, TIAN Y, et al. Sirtuin 3 and mitochondrial permeability transition pore (mPTP):a systematic review [J].Mitochondrion, 2022, 64: 103
[20] REN YH, HE X, YANG YT, et al. Mitochondria-mediated apoptosis and autophagy participate in buprofezin-induced toxic effects in non-target A549 cells [J].Toxics, 2022, 10(10):551
[21] FAN XJ, CHEN XY, LIU YJ, et al. Oxidative stress-mediated intrinsic apoptosis in human promyelocytic leukemia HL-60 cells induced by organic arsenicals [J].Sci Rep, 2016, 6(1):29865
[22] MAGDALENA C, IRWIN M, KAROLINA F, et al. Mitochondrial function are disturbed in the presence of the anticancer drug, 3-bromopyruvate [J].Int J Mol Sci, 2021, 22(12):6640
[23] 焦元红, 张晓卉, 徐娟, 等. 2-苯基苯并咪唑诱导的线粒体功能障碍 [J].化学试剂, 2023,45(5):59
JIAO YH,ZHANG XH,XU J, et al. Dysfunction in mitochondria induced by 2-phenyl benzimidazole[J].Chem Reagents,2023,45(5):59
[24] XU J, HE H, ZHOU L, et al. Pyridinium and indole orientation determines the mitochondrial uncoupling and anti-cancer efficiency of F16 [J].Eur J Med Chem, 2018, 154: 305
[25] LI D, HE H, LIN B, et al. Studies on the isolated mitochondrial damage induced by alpha-tocopheryl succinate and its interactions with human serum albumin [J].RSC Adv, 2014, 4(8):3913
[26] BARKHADE T, MAHAPATRA SK, BANERJEE I. Study of mitochondrial swelling, membrane fluidity and ROS production induced by nano-TiO2 and prevented by Fe incorporation [J].Toxicol Res, 2019, 8(5):711
[27] FUENTES-RETAMAL S,SANDOVAL-ACUNA C,PEREDO-SILVA L,et al. Complex mitochondrial dysfunction induced by tpp+-gentisic acid and mitochondrial translation inhibition by doxycycline evokes synergistic lethality in breast cancer cells [J].Cells, 2020, 9(2):407
[28] LIU Y, FAN X, ZHANG D, et al. Dual inhibition of pyruvate dehydrogenase complex and respiratory chain complex induces apoptosis by a mitochondria-targeted fluorescent organic arsenical in vitro and in vivo [J].Chem Med Chem, 2020, 15(6):552
[29] FAN XY, LIU YJ, CAI YM, et al. A mitochondria-targeted organic arsenical accelerates mitochondrial metabolic disorder and function injury [J].Bioorg Med Chem, 2019, 27(5):760
[30] 李东巍. 线粒体靶向抗肿瘤药物的合成和生物活性及其机理 [D]. 武汉:武汉大学, 2014
LI DW. Synthesis, Biological Activity and Mechanism of Mitochondrial Targeted Antitumor Drugs [D]. Wuhan: Wuhan University, 2014
[31] 章悦. 基于线粒体靶向的药(毒)物与线粒体和血清白蛋白的相互作用 [D]. 武汉:武汉大学, 2011
ZHANG Y. The Interaction between Drugs (toxins) and Mitochondria and Serum Albumin based on Mitochondrial Targeting [D] Wuhan: Wuhan University, 2011
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