Genotoxic activity of l-asparaginase produced by Streptomyces ansochromogenes UFPEDA 3420

Lacerda, Glêzia Renata da Silva; Cantalice, Jeanne Cristina Lapenda Lins; Lima, Gláucia Manoella de Souza; Albuquerque, Luiz Eduardo Felix de; Silva, Isllan D'Erik Gonçalves da; Mélo, Maria Eliane Bezerra de; Adam, Mônica Lúcia; Nascimento, Silène Carneiro do

doi:10.1007/s11274-019-2612-2

Cited by 6 publications

(6 citation statements)

References 45 publications

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“…ASNase is known to induce DNA damage and cause abnormalities in the cell cycle, which are manifested by cell cycle arrest and DNA breaks. Moreover, ASNase can induce micronucleus formation in normal cells and increase DNA breaks [17].…”

Section: Discussionmentioning

confidence: 99%

“…L-asparaginase can hydrolyze asparagine to aspartic acid. It is used in treating leukemia as its cells require asparagine for their survival and this enzyme deprives them of it leading to increased genotoxic effects [17]. Asparagine cannot be produced by the tumor cells.…”

Section: Introductionmentioning

confidence: 99%

“…As a result, bone marrow suppression is induced due to the inhibition of normal stem cell division by ASNase [19]. ASNase also enhances MN formation in normal and cultured cancer cells and leads to genotoxicity and DNA breaks [17].…”

Section: Introductionmentioning

confidence: 99%

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

Maleek

2022

Open Access Maced J Med Sci

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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 13th 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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Maleek

2022

Open Access Maced J Med Sci

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“…The therapeutic use of L-ASNases is limited by a variety of side effects: hepato- and nephrotoxicity, dysfunctions in the central nervous system, pancreatitis, thromboembolism, mucositis, hyperglycemia and dyslipidemia [ 16 , 17 , 18 ]. Moreover, genotoxic activity was shown for L-ASNase produced by Streptomyces ansochromogenes [ 19 ]. Such side effects are considered to be attributed to non-specific effects of these enzymes.…”

Section: Introductionmentioning

confidence: 99%

Molecular Analysis of L-Asparaginases for Clarification of the Mechanism of Action and Optimization of Pharmacological Functions

et al. 2022

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L-asparaginases (EC 3.5.1.1) are a family of enzymes that catalyze the hydrolysis of L-asparagine to L-aspartic acid and ammonia. These proteins with different biochemical, physicochemical and pharmacological properties are found in many organisms, including bacteria, fungi, algae, plants and mammals. To date, asparaginases from E. coli and Dickeya dadantii (formerly known as Erwinia chrysanthemi) are widely used in hematology for the treatment of lymphoblastic leukemias. However, their medical use is limited by side effects associated with the ability of these enzymes to hydrolyze L-glutamine, as well as the development of immune reactions. To solve these issues, gene-editing methods to introduce amino-acid substitutions of the enzyme are implemented. In this review, we focused on molecular analysis of the mechanism of enzyme action and to optimize the antitumor activity.

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“…L-asparaginase is an enzyme that can make asparagine into aspartic acid and ammonia. It is used to treat lymphoblastic leukemia, as these cells use asparagine for survival and this enzyme lowers them leading to an increase in genotoxic effects [17]. Tumor cells cannot synthesize these amino acids; therefore, tumor cells are killed by L-asparagine deficiency.…”

Section: Introductionmentioning

confidence: 99%

Effect of Lisinopril Treatment on Genotoxicity of L-Asparaginase (ASNase) in Bone Marrow Stem Cells for Aculte lymphoblstic Leukemia (ALL)

2022

IJCMER

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Background: Lisinopril is a drug used to lower blood pressure by blocking the angiotensin-converting enzyme (ACE). It measures the response of myeloid inflammation to bone marrow stem cells. L-asparaginase is a chemotherapeutic agent used to treat acute lymphoblastic leukemia (ALL) by increasing the genotoxicity of bone marrow stem cells. The purpose of this study was to find out the effect of Lisinopril on the genotoxicity of L-asparaginase (ASNase) in bone marrow cells. Materials and Methods: 60 Syrian hamster males’ are divided into three groups. The first group was treated with Lisinopril 10 mg / kg / day for 14 days. The second group was injected with L-asparaginase 3000 IU / kg. The third group was treated with Lisinopril for 14 days following the intraperitoneal injection of L-asparaginase (ASNase) at the end of day 13. Genotoxicity was assessed by calculating the micronucleus (MN) percentage and the mitotic index (MI). Results and Discussions: ASNase significantly increased genotoxicity by increasing% MN and lowering MI. When lisinopril was taken at 10 mg / kg / day, no significant effect was observed. However, a significant decrease in genotoxic effects was observed when mice received Lisinopril injected with 3000 IU / kg ASNase compared with the group treated with ASNase only. This result is shown by reducing% MN and increasing MI. Conclusion: The use of Lisinopril in the treatment of high blood pressure and its cancer treatment agent, L-asparaginase, was found to lower its genotoxicity in bone marrow cells.

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Genotoxic activity of l-asparaginase produced by Streptomyces ansochromogenes UFPEDA 3420

Cited by 6 publications

References 45 publications

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

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

Molecular Analysis of L-Asparaginases for Clarification of the Mechanism of Action and Optimization of Pharmacological Functions

Effect of Lisinopril Treatment on Genotoxicity of L-Asparaginase (ASNase) in Bone Marrow Stem Cells for Aculte lymphoblstic Leukemia (ALL)

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