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Purification and Biochemical Characterization of Native and Pegylated Form of L-Asparaginase from Aspergillus terreus and Evaluation of Its Antiproliferative Activity  [PDF]
Claudio Battiston Loureiro, Kleiton Silva Borges, Augusto Faria Andrade, Luiz Gonzaga Tone, Suraia Said
Advances in Microbiology (AiM) , 2012, DOI: 10.4236/aim.2012.22019
Abstract: L-asparaginase is a chemotherapeutic drug used in the treatment of lymphoblastic leukemia. In the present study, the extracellular L-asparaginase produced by strain (PC-1.7A) of Aspergillus terreus was purified, characterized, and modified with polyethylene glycol. Moreover, its antiproliferative activity was evaluated. The apparent molecular weight of the enzyme was found to be 136 kDa. The optimal pH and temperature for the enzyme were 9.0℃ and 40℃, respectively. The enzyme retained 100% of the activity at 40℃ for 120 min. Pegylated L-asparaginase was more thermostable and more resistant to trypsin than native enzyme. Native L-asparaginase against human normal cells did not show cytotoxicity. However, in the leukemia cell lines RS4;11 and HL60 the antiproliferative effects of native L-asparaginase were observed after 96 and 72 h of incubation, respectively. For the first time, an L-asparaginase from fungus was evaluated as an antitumor agent in human cells lines and further investigations should be conducted to improve the knowledge about this enzyme.
Statistical Screening of Supplementary Nitrogen Source for Enhanced Production of L-Asparaginase by Aspergillus terreus 1782
Baskar, G.,Renganathan, S.,Sriharini, C.,Sripriya, R.
- , 2010,
Abstract: Sa?etak In the present work, Latin Square Design (LSD) was applied to find the best supplementary nitrogen source for extracellular L-asparaginase production by Aspergillus terreus MTCC 1782 using corn flour as substrate in submerged fermentation. The independent effect of supplementary nitrogen source such as ammonium chloride, urea and sodium nitrate was studied on growth and production of L-asparaginase by A. terreus. Statistical significance of the nitrogen sources was studied by performing analysis of variance (ANOVA) and graphical ANOVA for LSD using Data plot software. It was found that there is no significant difference on growth due to the change in supplementary nitrogen source studied. Urea was identified as best supplementary nitrogen source with mean L-asparaginase production of 33.25 IU mL–1 and mean biomass production of 12.99 mg mL–1
Isolation and Characterization of L- Asparaginase Producing Endophytic Bacteria from Simarouba Gluaca
- , 2019,
Abstract: Cancer cells differentiate themselves from normal cells in diminished expression of L-asparaginase. It is the enzyme that catalyzes the hydrolysis of L-Asparagine to L-aspartic and ammonia, because of these it is used as a medication and in food manufacturing. As a medication L-aspraginase is used to treat various types of leukemia such as, acute lymphoblastic leukemia, acute myeloma leukemia and non Hodgkin’s lymphoma. Hence they are not capable of producing L-asparaginase and mainly depend on the L-asparagine from circulating plasma pools. The clinical action of this enzyme is attributed to the reduction of L-asparaginase, since tumor cells unable to synthesis these amino acids are selectively killed by L-asparaginase depravation. This enzyme is widely distributed, being found in as it is widely distributed bacteria as well as found in animals, microbes and plant sources. In the present study L-asparaginase producing bacteria was isolated from Simarouba glauca. It was grown on the modified M9 medium in which L- asparagine was the major source of L- asparaginase production was detected by the formation of pink colored zones on the medium. After the partial purification of the L-Asparaginase enzyme, the enzyme activity was found to be 155.83 Units/ml and specific activity of 779.15. The optimum pH was to be found at pH 8 at a temperature of 37°C in the presence of 10mM Mg2+. The molecular identification was done by16S rDNA, PCR and sequence analysis by BLAST further confirmed that Bacillus cereus
Side Effects of Vincristine and L-Asparaginase in Patients with Acute Lymphoblastic Leukemia in a Mexican Pediatric Hospital  [PDF]
Mario I. Ortiz, Sandra Rivera-Roldán, Marco A. Escamilla-Acosta, Georgina Romo-Hernández, Héctor A. Ponce-Monter, Rita Escárcega-ángeles
Pharmacology & Pharmacy (PP) , 2013, DOI: 10.4236/pp.2013.43050
Abstract:

Background: The treatment used to combat acute lymphoblastic leukemia (ALL) is multidrug; therefore it is important to use active pharmacovigilance to detect, assess and analyze the likely adverse reactions which may occur during the same period. Objective: To determine the frequency of adverse reactions to chemotherapeutic drugs in children with ALL. Material and Methods: Intensive pharmacovigilance was used to record the reports of adverse reactions to vincristine, L-asparaginase and the vincristine-L-asparaginase combination in children with ALL in a paediatric hospital. For each notification, the adverse reactions were analyzed in order to verify causality. Results: Forty patients were evaluated. Twenty children were female (50.0%) and 20 were male (50%). The children had a mean age, weight and height (±standard deviation: SD) of 8.1 (±3.4) years, 31.4 (±13.9) kg and 1.3 (±0.2) m, respectively. Vincristine was administered to 19 patients, vincristine plus L-asparaginase were given to 19 patients and only 2 patients used L-asparaginase. One-hundred-ninety adverse reactions were detected in the patients, with an average (±SD) of 4.8 (±2.6). Ondansetron was the drug administered for the treating of nausea and vomiting. One hundred eighty-one (95.3%) adverse reactions were identified as “definite”, 5 (2.6%) as “probable” and 4 (2.1%) as “doubtful”. Conclusions: There is a high incidence of adverse reactions by the administration of vincristine and L-asparaginase; the reactions of highest incidence were: nausea, vomiting, neutropenia,

5. L-asparaginase production and molecular identification of marine streptomycete strain WS3/1
P.V. Kamala Kumari,G. Girija Sankar,T. Prabhakar
International Journal of Pharmaceutical and Biomedical Research (IJPBR) , 2011,
Abstract: The aim of the present study is the production and molecular identification of L-asparaginase from marine Streptomycete sp. WS3/1. Sixty seven actinomycetes were isolated from marine sediments of Tuticorn, Tamilnadu by rapid assay plate method. Based on the enzyme activity, the most potent strain was selected and identified. The morphological, cultural and biochemical characteristics of the identified strain revealed it to a member of the genus Streptomyces. A total of sixty seven marine actinomycetes were isolated out of which thirty two showed promising enzyme activity. Based on morphological, cultural, biochemical characteristics, Scanning Electron Microscopy, the potent strain was designated as Streptomyces griseoluteus WS3/1. The nucleotide sequence of the 16S rDNA gene analysis of the potent strain showed 99% similarity with Streptomyces. This investigation indicates that marine sediments are promising source for isolation of marine actinomycetes particularly streptomyces. Marine streptomyces sp. strain WS3/1 is the first report on the strain identification of marine streptomyces with high levels of extracellular L-asparaginase enzyme production.
Hyperglycemia risk factors in leukemia: Case report
Fatih Erbey,Dilek Do?ruel,?brahim Bayram,Bilgin Yüksel
Medical Journal of Bakirk?y , 2006,
Abstract: Asparaginase is an enzyme used in the treatment of leukemia. Its antileucemic effect is believed to result from the depletion of circulating asparagine. Major side effects are anaphylaxis, pancreatitis, diabetes, coagulation abnormalities, and thrombosis. Hyperglycemia is a well known but a rare side effect of L-asparaginase (L-ASP). The reported incidences vary widely from 1% to 14% in recipients of L-ASP alone, 2 to 11% in recipients of both L-ASP and prednisone, and only about 0.2% in those receiving prednisone alone. Age, obesity and Down syndrome were contributing factors to the increased risk of hyperglycemia. We evaluate hyperglycemia risk factors in leukemia by presenting a case who develops hyperglycemia during the treatment.
CHARACTERIZATION OF l-ASPARAGINASE PRODUCING BACTERIA FROM WATER, FARM AND SALINE SOIL
K D Kamble,L H Kamble,M Musaddiq
Bioscience Discovery , 2012,
Abstract: The habitat chosen for screening the bacteria were farm soil, saline soil and water. The activity was detected on a medium containing 1% peptone, 0.6% beef extract, 0.33% KH3PO4, 0.1% L-asparagine and phenol red. L-asparaginase activity was detected on the basis of formation of red colour around the colony. Likewise efficient L- asparaginase producing bacteria were screened. These were then studied for routine microbiological and biochemical characterization. The microorganisms we characterized belonged to the genera E.coli, Serratia spp., Pseudomonas aeruginosa, Bacillus spp., Aeromonas species and Proteus spp. L-asparaginase from halophilic bacteria is expected to be non-allergic and hence halophilic bacteria from saline soil can contribute to therapeutic value of this enzyme.
Activation of L-Asparaginase in Escherichia coli by Rosmarinic Acid and Effect of Ferrous Ions on the Increasing Antibacterial Activity of Rosmarinic Acid
迷迭香酸对大肠杆菌L-天冬酰胺酶的激活及亚铁离子对迷迭香酸的抗菌增效作用

LI Ming-Zhe,LIU Xiao-Qian,SHAO Nan,LI Rong-Gui,
李明喆
,刘晓倩,邵 楠,李荣贵

微生物学通报 , 2009,
Abstract: Effect of rosmarinic acid on the kinetics of L-asparaginase catalyzed reaction was studied. The result showed that rosmarinic acid could reduce the apparent kinetic parameters (apparent Michaelis-Menten constant, Kmapp) of the enzyme, which indicated that rosmarinic acid was an activator of L-asparaginase. Ferrous ions could increase the antibacterial activity of rosmarinic acid. Absorption spectra analysis indicated that there existed a direct interaction between rosmarinic acid and ferrous ions, with a mole ratio of 1:1.
Diabetes melito transitório relacionado à terapia com L-asparaginase
Alves, Crésio;Chaves, Carina;Souza, Mabel;
Arquivos Brasileiros de Endocrinologia & Metabologia , 2007, DOI: 10.1590/S0004-27302007000400020
Abstract: treatment of hematological malignancies with l-asparaginase has been associated with diabetes mellitus in about 1-2% of patients. the concomitant use of steroids has an additional deleterious effect. in this article, we report the occurrence of diabetes in a 13 year-old girl treated with l-asparaginase and dexamethasone for acute lymphoblastic leukemia. the diabetes developed 120 days after the drug was started, requiring insulin therapy for 12 months. anti-islet autoantibody was negative, and there were no laboratory findings suggestive of pancreatitis. the dm related do l-asparaginase therapy is insulinopenic and transient, resolving with suspension of the drug. the diagnosis of this type of diabetes is based on its temporal relationship with the l-asparaginase and in the exclusion of other known causes. there is no laboratory test capable of elucidating the diagnosis. therefore, investigation to rule out type 1a dm, type 1b dm, insulin-resistant dm induced by corticotherapy and dm secondary to toxic pancreatitis is of utmost importance. the insulin therapy must be followed closely, since this is a transient form of diabetes.
The Effects of L-Asparaginase on Blood Triglycerides, Glucose, and Albumin Levels and Coagulation State in ALL Patients in Pediatric Ward
Bani-Hashem Abdullah,Heydarian Farhad,Hiradfar Simin,Ehteshammanesh Hojatullah
Acta Medica Iranica , 2009,
Abstract: Asparaginase is one of the most important agents in the treatment of ALL. However, it has some side effects including dislipidemia, hyperglycemia, coagulopathy and hepatotoxicity. We studied its side ef-fects on our patients. The effects of L-asparaginase were assessed on 25 new ALL patients (case group) and 25 patients with known ALL who had completed their treatment before. Sixty two percent of cases were male and remainder was female. The mean age of patients was 7.2 ± 3.8 years. In our patients, there was a rise in triglycerides (TG) was seen following L- asparaginase administration (P = 0.02). Also, PT prolongation (P = 0.02) and hypoalbominemia (P = 0.002) were detected which could PT prolongation and hypoalbuminemia may be seen with L-asparaginase therapy that can be prevented with transfusion of FFP. Hypertriglyceridemia is often asymptomatic with no need for therapy.
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