Lisinopril Can Reduce Genotoxicity of L-Asparaginase in Bone Marrow Stem Cells

Muthana Ibrahim Maleek

doi:10.3889/oamjms.2022.9726

Authors

Muthana Ibrahim Maleek Department of Biology, College of Sciences, Wasit University, Kut, Wasit, Iraq

DOI:

https://doi.org/10.3889/oamjms.2022.9726

Keywords:

Lisinopril, L-asparaginase, Angiotensin-converting enzyme, Genotoxicity, Stem cells, Bone marrow, Mitotic index, Micronucleus

Abstract

BACKGROUND: Lisinopril is a medication used to lower blood pressure by inhibiting the angiotensin-converting enzyme (ACE). L-asparaginase is a chemotherapeutic agent used to treat acute lymphoblastic leukemia.

AIM: To Study the effect of lisinopril on the genotoxicity of L-asparaginase (ASNase) in bone marrow stem cells.

METHODS: Albino Swiss male mice were divided into three groups. The first group was treated with lisinopril 10 mg/kg/day for 14 days. The second group mice were injected with L-asparaginase 3000 IU/kg. The last group was treated with of lisinopril for 14 days followed with an intraperitoneal injection of L-asparaginase (ASNase) at the end of the 13^th day. Genotoxicity was assessed by calculating the percentage of micronucleus (MN) and mitotic index (MI).

RESULTS: ASNase significantly increased genotoxicity by raising the %MN and lowering % MI. When Lisinopril 10 mg/kg/day was administered no significant effect was seen. However, a significant decrease in genotoxic effects was observed when mice receiving Lisinopril were injected with 3000 IU/kg ASNase as compared the group treated with ASNase alone. This effect was manifested by decreasing %MN and increasing %MI.

CONCLUSION: Using lisinopril for blood hypertension treatments concurrently with the cancer therapeutic agent, L- asparaginase, decreased its genotoxicity in bone marrow stem cells.

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References

Potier L, Roussel R, Elbez Y, Marre M, Zeymer U, Reid CM, et al. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high vascular risk. Heart. 2017;103(17):1339. https://doi.org/10.1136/heartjnl-2016-310705 PMid:28285267 DOI: https://doi.org/10.1136/heartjnl-2016-310705

Yang Y, Tian T, Wang Y, Li Z, Xing K, Tian G. SIRT6 protects vascular endothelial cells from angiotensin II-induced apoptosis and oxidative stress by promoting the activation of Nrf2/ARE signaling. Eur Pharmacol. 2019;859:172516. https://doi.org/10.1016/j.ejphar.2019.172516 PMid:31265839 DOI: https://doi.org/10.1016/j.ejphar.2019.172516

Rudi WS, Molitor M, Garlapati V, Finger S, Wild J, Münzel T, et al. Ace inhibition modulates myeloid hematopoiesis after acute myocardial infarction and reduces cardiac and vascular inflammation in ischemic heart failure. Antioxidants (Basel). 2021;10(3):396. https://doi.org/10.3390/antiox10030396 PMid:33807982 DOI: https://doi.org/10.3390/antiox10030396

Avsar T, Yigi BN, Turan G, Altunsu D, Calis S, Kur B, et al. Development of imidazolone based angiotensin II receptor Type I inhibitor small molecule as a chemotherapeutic agent for cell cycle inhibition. All Life. 2021;14(1):1678-90. https://doi.org/10.1080/26895293.2021.1954098 DOI: https://doi.org/10.1080/26895293.2021.1954098

Zimnol A, Spicker N, Balhorn R, Schröder K, Schupp N. The NADPH oxidase isoform 1 contributes to angiotensin II-mediated DNA damage in the kidney. Antioxidants (Basel). 2020;9(7):586. https://doi.org/10.3390/antiox9070586 PMid:32635630 DOI: https://doi.org/10.3390/antiox9070586

Seretis A, Cividini S, Markozannes G, Tseretopoulou X, Lopez DS, Ntzani EE, et al. Association between blood pressure and risk of cancer development: A systematic review and meta-analysis of observational studies. Sci Rep. 2019;9(1):8565. https://doi.org/10.1038/s41598-019-45014-4 PMid:31189941 DOI: https://doi.org/10.1038/s41598-019-45014-4

Sobczuk P, Szczylik C, Porta C, Czarnecka AM. Renin angiotensin system deregulation as renal cancer risk factor. Oncol Lett. 2017;14(5):5059-68. https://doi.org/10.3892/ol.2017.6826 PMid:29098020 DOI: https://doi.org/10.3892/ol.2017.6826

Sorich MJ, Kichenadasse G, Rowland A, Woodman RJ, Mangoni AA. Angiotensin system inhibitors and survival in patients with metastatic renal cell carcinoma treated with VEGF-targeted therapy: A pooled secondary analysis of clinical trials. Int J Cancer. 2016;138(9):2293-9. https://doi.org/10.1002/ijc.29972 PMid:26685869 DOI: https://doi.org/10.1002/ijc.29972

Perkhofer L, Gout J, Roger E, De Almeida FK, Simões CB, Wiesmüller L, et al. DNA damage repair as a target in pancreatic cancer: State-of-the-art and future perspectives. BMJ. 2021;70(3):606-17. https://doi.org/10.1136/gutjnl-2019-319984 DOI: https://doi.org/10.1136/gutjnl-2019-319984

Pilger D, Seymour LW, Jackson SP. Interfaces between cellular responses to DNA damage and cancer immunotherapy. Gene Dev. 2021;35(9-10):602-18. https://doi.org/10.1101/gad.348314.121 PMid:33888558 DOI: https://doi.org/10.1101/gad.348314.121

Huang R, Zhou PK. DNA damage repair: Historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy. Signal Transduct Target Ther. 2021;6(1):254. https://doi.org/10.1038/s41392-021-00648-7 PMid:34238917 DOI: https://doi.org/10.1038/s41392-021-00648-7

Sommer S, Buraczewska I, Kruszewski M. Micronucleus assay: The state of art, and future directions. Int J Mol Sci. 2020;21(4):1534. https://doi.org/10.3390/ijms21041534 PMid:32102335 DOI: https://doi.org/10.3390/ijms21041534

Krupina K, Goginashvili A, Cleveland DW. Causes and consequences of micronuclei. Curr Opin Cell Biol. 2021:70:91-9. https://doi.org/10.1016/j.ceb.2021.01.004 PMid:33610905 DOI: https://doi.org/10.1016/j.ceb.2021.01.004

Udroiu I, Sgura A. Quantitative relationships between acentric fragments and micronuclei: New models and implications for curve fitting. Int J Radiat Biol. 2020;96(2):197-205. https://doi.org/10.1080/09553002.2020.1683638 PMid:31633434 DOI: https://doi.org/10.1080/09553002.2020.1683638

Liu S, Kwon M, Mannino M, Yang N, Renda F, Khodjakov A, et al. Nuclear envelope assembly defects link mitotic errors to chromothripsis. Nature. 2018;561(7724):551-5. https://doi.org/10.1038/s41586-018-0534-z PMid:30232450 DOI: https://doi.org/10.1038/s41586-018-0534-z

Öztürk S, İrkin LC. Experimental 70% hepatectomy model: Apoptotic index, proliferative index and mitotic index. Sakarya U J Sci. 2021;25(3):788-99. https://doi.org/10.16984/saufenbilder.886245 DOI: https://doi.org/10.16984/saufenbilder.886245

Da Silva Lacerda GR, Cantalice JC, De Souza Lima GM, De Albuquerque LE, Da Silva ID, De Melo ME, Adam ML, Do Nascimento SC. Genotoxic activity of L-asparaginase produced by streptomyces ansochromogenes UFPEDA 3420. World J Microb Biot. 2019;35(3):41. https://doi.org/10.1007/s11274-019-2612-2 PMid:30762133 DOI: https://doi.org/10.1007/s11274-019-2612-2

El-Fakharany F, Orabi H, Abdelkhalek E, Sidkey N. Purification and biotechnological applications of L-asparaginase from newly isolated Bacillus halotolerans OHEM18 as antitumor and antioxidant agent. J Biomol Struct Dyn. 2022:40(9):3837-49. https://doi.org/10.1080/07391102.2020.1851300 PMid:33228468 DOI: https://doi.org/10.1080/07391102.2020.1851300

Chen T, Zhang J, Zeng H, Zhang Y, Zhang Y, Zhou X, et al. Antiproliferative effects of Lasparaginase in acute myeloid leukemia. Exp Ther Med. 2020;20(3):2070-8. https://doi.org/10.3892/etm.2020.8904 PMid:32782519 DOI: https://doi.org/10.3892/etm.2020.8904

Rafael-Fortney JA, Chimanji NS, Schill KE, Martin CD, Murray JD, Ganguly R, et al. Early treatment with lisinopril and spironolactone preserves cardiac and skeletal muscle in duchenne muscular dystrophy mice. Circulation. 2011;124(5):582-8. https://doi.org/10.1161/CIRCULATIONAHA.111.031716 PMid:21768542 DOI: https://doi.org/10.1161/CIRCULATIONAHA.111.031716

Ehsanipour EA, Sheng X, Behan JW, Wang X, Butturini A, Avramis VI, et al. Adipocytes cause leukemia cell resistance to L-asparaginase via release of glutamine. Cancer Res. 2013;73(10):2998-3006. https://doi.org/10.1158/0008-5472.CAN-12-4402 PMid:23585457 DOI: https://doi.org/10.1158/0008-5472.CAN-12-4402

Allen JW, Schuler CF, Mendes RW, Latt SA. A simplified technique for in vivo analysis of sister-chromatid exchange using 5-bromodeoxyuridine tablets. Cytogenet Cell Genet. 1977;18(4):231-7. https://doi.10.1159/000130765 PMid:872628 DOI: https://doi.org/10.1159/000130765

Schmid W. The micronucleus test. Mutat Res. 1975;31(1):9-15. https://doi.org/10.1016/0165-1161(75)90058-8 PMid:48190 DOI: https://doi.org/10.1016/0165-1161(75)90058-8

Singh N, Sharma B. Role of toxicants in oxidative stress mediated DNA damage and protection by phytochemicals. EC Pharmacol Toxicol. 2019;7(5):325-30.

Salehi F, Behboudi H, Kavoosi G, Ardestani SK. Oxidative DNA damage induced by ROS-modulating agents with the ability to target DNA: A comparison of the biological characteristics of citrus pectin and apple pectin. Sci Rep. 2018;l8(1):3902. https://doi.org/10.1038/s41598-018-32308-2 PMid:30224635 DOI: https://doi.org/10.1038/s41598-018-32308-2

Yang H, Villani RM, Wang H, Simpson MJ, Roberts MS, Tang M, et al. The role of cellular reactive oxygen species in cancer chemotherapy. J Exp Clin Cancer Res. 2018;37(1):266. https://doi.org/10.1186/s13046-018-0909-x PMid:30382874 DOI: https://doi.org/10.1186/s13046-018-0909-x

Yamamoto H, Shibuya K, Fukushima T, Hashizume T. Effects of antioxidant capacity on micronucleus induction by cigarette smoke in mammalian cells. Mutat Res Genet Toxicol Enviroin Mutagen. 2022:873:503427. https://doi.org/10.1016/j.mrgentox.2021.503427 Mid:35094812 DOI: https://doi.org/10.1016/j.mrgentox.2021.503427

OECD. OECD Guidelines for the Testing of Chemicals, Section 4: Health Effects. Test No. 487: In Vitro Mammalian Cell Micronucleus Test. Paris, France: OECD Publishing; 2016. https://doi.org/10.1787/20745788 DOI: https://doi.org/10.1787/20745788

Ruiz-Ruiz B, Arellano-García ME, Radilla-Chavez P, Salas-Vargas DS, Toledano-Magaña Y, Casillas-Figueroa F, et al. Cytokinesis-block micronucleus assay using human lymphocytes as a sensitive tool for cytotoxicity/genotoxicity evaluation of AgNPs. ACS Omega. 2020;5(21):12005-15. https://doi.org/10.1021/acsomega.0c00149 PMid:32548379 DOI: https://doi.org/10.1021/acsomega.0c00149

Saatci C, Erdem Y, Bayramov R, Akalın H, Tascioglu N, Ozkul Y. Effect of sodium benzoate on DNA breakage, micronucleus formation and mitotic index in peripheral blood of pregnant rats and their newborns. Biotechnol Biotechnol Equip. 2016:30:1179-83. https://doi.org/10.1080/13102818.2016.1224979 DOI: https://doi.org/10.1080/13102818.2016.1224979

Baskar G, Chandhuru J, Fahad KS, Praveen AS, Chamundeeswari M, Muthukumar T. Anticancer activity of fungal L-Asparaguses conjugated with zinc oxide nanoparticles. J Mater Sci Mater Med. 2015;26(1):5380. https://doi.org/10.1007/s10856-015-5380-z PMid:25589205 DOI: https://doi.org/10.1007/s10856-015-5380-z

Talluri VP, Bhavana M, Kumar MM, Rajagopal SV. L-asparaginase: An ultimate anti-neoplastic enzyme. Int Lett Nat Sci. 2014;15:23-35. https://doi.org/10.18052/www.scipress.com/ILNS.15.23 DOI: https://doi.org/10.18052/www.scipress.com/ILNS.15.23