Attenuation of LPS-Induced Lung Injury by Benziodarone Via Reactive Oxygen Species Reduction

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jun 28

PMID 37373184

Authors

Tsutomu Ishihara

Ken-Ichiro Tanaka

Ayaka Takafuji

Keita Miura

Tohru Mizushima

Affiliations

Soon will be listed here.

Abstract

As overproduction of reactive oxygen species (ROS) causes various diseases, antioxidants that scavenge ROS, or inhibitors that suppress excessive ROS generation, can be used as therapeutic agents. From a library of approved drugs, we screened compounds that reduced superoxide anions produced by pyocyanin-stimulated leukemia cells and identified benzbromarone. Further investigation of several of its analogues showed that benziodarone possessed the highest activity in reducing superoxide anions without causing cytotoxicity. In contrast, in a cell-free assay, benziodarone induced only a minimal decrease in superoxide anion levels generated by xanthine oxidase. These results suggest that benziodarone is an inhibitor of NADPH oxidases in the plasma membrane but is not a superoxide anion scavenger. We investigated the preventive effect of benziodarone on lipopolysaccharide (LPS)-induced murine lung injury as a model of acute respiratory distress syndrome (ARDS). Intratracheal administration of benziodarone attenuated tissue damage and inflammation via its ROS-reducing activity. These results indicate the potential application of benziodarone as a therapeutic agent against diseases caused by ROS overproduction.

Citing Articles

Reactive Oxygen Species and Strategies for Antioxidant Intervention in Acute Respiratory Distress Syndrome.

Lim E, Lee S, Shin H, Kim G Antioxidants (Basel). 2023; 12(11).

PMID: 38001869 PMC: 10669909. DOI: 10.3390/antiox12112016.

References

Heumuller S, Wind S, Barbosa-Sicard E, Schmidt H, Busse R, Schroder K . Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension. 2007; 51(2):211-7. DOI: 10.1161/HYPERTENSIONAHA.107.100214. View

Jaquet V, Scapozza L, Clark R, Krause K, Lambeth J . Small-molecule NOX inhibitors: ROS-generating NADPH oxidases as therapeutic targets. Antioxid Redox Signal. 2009; 11(10):2535-52. DOI: 10.1089/ars.2009.2585. View

Altenhofer S, Radermacher K, Kleikers P, Wingler K, Schmidt H . Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement. Antioxid Redox Signal. 2014; 23(5):406-27. PMC: 4543484. DOI: 10.1089/ars.2013.5814. View

Ishihara T, Shibui M, Hoshi T, Mizushima T . Scavenging of superoxide anions by lecithinized superoxide dismutase in HL-60 cells. Mol Biosyst. 2015; 12(1):274-82. DOI: 10.1039/c5mb00631g. View

Smelcerovic A, Tomovic K, Smelcerovic Z, Petronijevic Z, Kocic G, Tomasic T . Xanthine oxidase inhibitors beyond allopurinol and febuxostat; an overview and selection of potential leads based on in silico calculated physico-chemical properties, predicted pharmacokinetics and toxicity. Eur J Med Chem. 2017; 135:491-516. DOI: 10.1016/j.ejmech.2017.04.031. View

Rana P, Will Y, Nadanaciva S, Jones L . Development of a cell viability assay to assess drug metabolite structure-toxicity relationships. Bioorg Med Chem Lett. 2016; 26(16):4003-6. DOI: 10.1016/j.bmcl.2016.06.088. View

Bedard K, Krause K . The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007; 87(1):245-313. DOI: 10.1152/physrev.00044.2005. View

Inoue M, Watanabe N, Utsumi T, Sasaki J . Targeting SOD by gene and protein engineering and inhibition of free radical injury. Free Radic Res Commun. 1991; 12-13 Pt 1:391-9. DOI: 10.3109/10715769109145809. View

Watanabe K, Tanaka M, Yuki S, Hirai M, Yamamoto Y . How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis?. J Clin Biochem Nutr. 2018; 62(1):20-38. PMC: 5773834. DOI: 10.3164/jcbn.17-62. View

10.

Aldieri E, Riganti C, Polimeni M, Gazzano E, Lussiana C, Campia I . Classical inhibitors of NOX NAD(P)H oxidases are not specific. Curr Drug Metab. 2008; 9(8):686-96. DOI: 10.2174/138920008786049285. View

11.

Brechard S, Brunello A, Bueb J, Tschirhart E . Modulation by cADPr of Ca2+ mobilization and oxidative response in dimethylsulfoxide- or retinoic acid-differentiated HL-60 cells. Biochim Biophys Acta. 2006; 1763(1):129-36. DOI: 10.1016/j.bbamcr.2005.12.003. View

12.

Droge W . Free radicals in the physiological control of cell function. Physiol Rev. 2002; 82(1):47-95. DOI: 10.1152/physrev.00018.2001. View

13.

Drummond G, Selemidis S, Griendling K, Sobey C . Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov. 2011; 10(6):453-71. PMC: 3361719. DOI: 10.1038/nrd3403. View

14.

El-Benna J, Hurtado-Nedelec M, Marzaioli V, Marie J, Gougerot-Pocidalo M, Dang P . Priming of the neutrophil respiratory burst: role in host defense and inflammation. Immunol Rev. 2016; 273(1):180-93. DOI: 10.1111/imr.12447. View

15.

Yang S, Lian G . ROS and diseases: role in metabolism and energy supply. Mol Cell Biochem. 2019; 467(1-2):1-12. PMC: 7089381. DOI: 10.1007/s11010-019-03667-9. View

16.

Kim J, Neupane G, Lee E, Jeong B, Park B, Thapa P . NADPH oxidase inhibitors: a patent review. Expert Opin Ther Pat. 2011; 21(8):1147-58. DOI: 10.1517/13543776.2011.584870. View

17.

Lee M, Graham G, Williams K, Day R . A benefit-risk assessment of benzbromarone in the treatment of gout. Was its withdrawal from the market in the best interest of patients?. Drug Saf. 2008; 31(8):643-65. DOI: 10.2165/00002018-200831080-00002. View

18.

Sies H, Berndt C, Jones D . Oxidative Stress. Annu Rev Biochem. 2017; 86:715-748. DOI: 10.1146/annurev-biochem-061516-045037. View

19.

Chen H, Zhang B, Yao Y, Chen N, Chen X, Tian H . NADPH oxidase-derived reactive oxygen species are involved in the HL-60 cell monocytic differentiation induced by isoliquiritigenin. Molecules. 2012; 17(11):13424-38. PMC: 6268504. DOI: 10.3390/molecules171113424. View

20.

Kolaczkowska E, Kubes P . Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013; 13(3):159-75. DOI: 10.1038/nri3399. View