scholarly journals TOXICOLOGICAL PROPERTIES OF BIOMODIFIED ENZYME DRUG - L-ASPARAGINASE WAS79

2015 ◽  
Vol 14 (4) ◽  
pp. 53-58
Author(s):  
E. R. Pereverzeva ◽  
I. D. Treschalin ◽  
E. V. Voznyakovskaya ◽  
M. I. Treschalin ◽  
T. B. Pereverzeva ◽  
...  

Toxicological study of L-asparaginase Was79, obtained by modification of native enzyme Wolinella succinogenes in Research Institute of Genetics and Selection, was performed in male and female inbred rats. L-asparaginase was injected intraperitoneally at the 1 and 10 therapeutic dose (15x1200 IU/kg or 15x12000 IU/kg with 24-h interval). Dynamics of body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed for all animals. Five animals in each group were sacrificed 1 and 15 days post treatment. At necropsy, the organs were inspected macroscopically. The mass coefficients of heart, kidneys, liver, spleen and thymus were calculated. The pathomorphological evaluation was performed for internal organs. The results of the study demonstrate that the treatment with L-asparaginase Was79 did not produce any changes in body weight, hematology, blood biochemical or urinary parameters. Hematological, renal, gastrointestinal, and pancreatic toxicity of L-asparaginase have been documented only by microscopic pathology observation. Liver toxicity, revealed in the histopathological findings, was supported by the results of clinical chemistry. Marked elevation of ALT and alkaline phosphatase in serum was found in both treated groups. Most of these abnormalities were reversible and dose-dependent.

Author(s):  
M. I. Uneze ◽  
D. N. Azionu

Various parts of psidium guajava linn are used in ethnomedicine in controls and treatments of different disorders such as liver, heart, and blood related disorders [11]. This research work investigate qualitative phytochemical composition of ethanol leaf extract of psidium guajava linn and its effect on some hematological parameters in albino rats. Qualitative phytochemical analysis of the extract was performed by standard procedures. A total of 20 adult male albino rats were used, they were randomly placed into 5 groups (A, B, C, D and E) each group containing 4 rats groups A, B, C, and D were administered, via oral intubation, the extract at doses of 200, 400, 600, and 800 mg/kg body weight respectively of the extract for 7 consecutive days. Phytochemical screening shows that the extract was rich in tannins anthraquinones, and flavonoid while alkaloids, saponins, terpenes and glycoside were slightly present. There was a decrease in the average body weight, physical activities, and feed and water intake of the rats in the test groups relative to the control hemoglobin concentrate, total white blood cell and packed cell volume recorded in the groups  administered the extract were significantly (p<0.05) higher than in the control this effect on  the haemotological parameters was found to be dose dependent. The findings of this study suggest that the aqueous extract of the fruit plants may be useful in control and treatment of blood related disorders.  These useful applications may be as a result of the phytochemical present in the extract.


2020 ◽  
Vol 15 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Hossein Mahmoudvand ◽  
Mahbobeh Pakravanan ◽  
Farnaz Kheirandish ◽  
Sareh Jahanbakhsh ◽  
Maryam Sepahvand ◽  
...  

Background: The present work aimed to evaluate the chemical composition of Curcuma zadoaria essential oil and to investigate its efficacy and safety against hydatid cyst protoscoleces. Methods: Collected protoscoleces from liver fertile hydatid cysts of infected sheep were exposed to different concentrations of the essential oil (75, 150, 300 μl/mL) for 5-30 min in vitro and ex vivo. Then, by using the eosin exclusion assay, the viability of protoscoleces was studied. In the next step, 24 male NMRI mice were examined to assess the toxicity of C. zadoaria essential oil by measuring the biochemical and hematological parameters. Results: Based on the obtained results, the LD50 value of intraperitoneal injection of the C. zadoaria essential oil was 1.76 mL/kg of body weight and the maximum non-fatal dose was 0.96 mL/kg of body weight. C. zadoaria essential oil had a strong proto scolicidal activity in vitro so that at the 300 and 150 μl/ml entirely eliminates the parasite after 5 and 10 minutes; whereas, weak proto scolicidal activity was observed at lower doses. Ex vivo assay, no similar effect with in vitro was observed, therefore, more time is required to show a potent proto scolicidal activity. C. zadoaria essential oil at the concentrations of 300 and 150 μl/mL after an exposure time of 7 and 12 min, killed 100% of protoscoleces within the hydatid cyst, respectively. After intraperitoneal injection of the C. zadoaria essential oil for 2 weeks, no significant difference (p > 0.05) was observed in the clinical chemistry and hematologic parameters at the doses of 0.15, 0.3, 0.6 mL/kg. Conclusion: The obtained results in vitro and ex vivo exhibited that C. zadoaria essential oil had a favorable proto scolicidal activity on hydatid cyst protoscoleces. However, more supplementary works are required to verify these findings by assessing clinical subjects.


2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Sittichai Koontongkaew ◽  
Orapan Poachanukoon ◽  
Seewaboon Sireeratawong ◽  
Thaweephol Dechatiwongse Na Ayudhya ◽  
Parirat Khonsung ◽  
...  

Zingiber cassumunar Roxb. has been used for traditional medicine, but few studies have described its potential toxicity. In this study, the acute and chronic oral toxicity of Z. cassumunar extract granules were evaluated in Sprague-Dawley rats. The extract at a single dose of 5000 mg/kg body weight did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. However, a decrease in body weights was observed in treated males (P<0.05). The weights of lung and kidney of treated females were increased (P<0.05). Treated males were increased in spleen and epididymis weights (P<0.05). In repeated dose 270-day oral toxicity study, the administration of the extracts at concentrations of 0.3, 3, 30, 11.25, 112.5, and 1,125 mg/kg body weight/day revealed no-treatment toxicity. Although certain endpoints among those monitored (i.e., organ weight, hematological parameters, and clinical chemistry) exhibited statistically significant effects, none was adverse. Gross and histological observations revealed no toxicity. Our findings suggest that the Z. cassumunar extract granules are well tolerated for both single and chronic administration. The oral no-observed-adverse-effect level (NOAEL) for the extract was 1,125 mg/kg body weight/day for males and females.


1987 ◽  
Vol 6 (4) ◽  
pp. 471-478 ◽  
Author(s):  
J. R. Hayes ◽  
L. W. Condie ◽  
J. L. Egle ◽  
J. F. Borzelleca

Trans-1,2-dichloroethylene was administered either by gavage (acute studies) or in drinking water (subchronic studies) to male and female Sprague-Dawley derived Charles River rats. The acute oral LD50 was 7902 mg/kg for males and 9939 mg/kg for females. Decreased activity, ataxia, and depressed respiration preceded death. In the subchronic study, rats received theoretical daily doses of 500, 1500, and 3000 mg trans-1,2-dichloroethylene/kg body weight/day for 90 consecutive days. The actual daily doses were 402, 1314, and 3114 mg/kg for males and 353, 1257, and 2809 mg/kg for females. There were no compound-related deaths. There were no consistently significant compound-related dose-dependent adverse effects on any of the hematological, serological, or urinary parameters evaluated. There were dose-dependent increases in kidney weights and ratios in treated females. There were no compound-related gross or histological effects. No specific organ site toxicity could be identified in these studies. These data suggest that the toxicity from exposure to trans-1,2-dichloroethylene in drinking water apparently is low and probably does not constitute a serious health hazard.


Toxins ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 435 ◽  
Author(s):  
Igor Mrdjen ◽  
Mark Morse ◽  
Randall Ruch ◽  
Thomas Knobloch ◽  
Shambhunath Choudhary ◽  
...  

Microcystin (MC) exposure is an increasing concern because more geographical locations are covered with cyanobacterial blooms as eutrophication and bloom-favoring environmental factors become more prevalent worldwide. Acute MC exposure has been linked to gastrointestinal distress, liver toxicity, and death in extreme circumstances. The goal of this study was to provide an accurate and comprehensive description of MC-LRs impacts on liver pathology, clinical chemistry, and gap junction intercellular communication (GJIC) in CD-1 male and female mice. Mice were exposed to 0, 3000, and 5000/4000 µg/kg/day MC-LR, daily for 7 days, and were necropsied on Day 8. Blood samples for clinical chemistry analysis were processed to serum, while liver sections were fixed for histopathology or evaluated for GJIC using fluorescent cut-load dye. Results show a dose-dependent relationship with MC-LR exposure and hepatocellular hypertrophy, degradation, and necrosis. Clinical chemistry parameters alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and cholesterol increased significantly in MC-LR exposed mice. Clinical chemistry parameter analysis showed significantly increased susceptibility to MC-LR in females compared to males. Changes in GJIC were not noted, but localization of hepatotoxicity near the central veins and midlobular areas was seen. Future toxicity studies involving MCs should consider response differences across sexes, differing MC congeners, and combinatorial exposures involving other cyanotoxins.


2018 ◽  
Vol 17 (3) ◽  
pp. 81-88 ◽  
Author(s):  
M. I. Treschalin ◽  
I. D. Treschalin ◽  
V. A. Golibrodo ◽  
A. E. Shchekotikhin ◽  
E. R. Pereverzeva

Introduction.New antitumor multitarget drug LCTA-2034, obtained in Gause Institute of New Antibiotics, has demonstrated high activity against prognostically significant transplantable mice tumors by the oral application.Objective.To investigate the toxicological properties of LCTA-2034 by the oral route of administration on rats.Materials and methods.Toxicological study of LCTA-2034 was performed on 30 male Wistar rats. Drug substance dissolved in potable water. 2 % solution was administrated per os at the 1 and 5 therapeutic dose (15 × 20 mg/kg or 15 × 100 mg/kg with 24-h interval). During the study dynamics of body weight, hematological parameters, blood biochemical parameters, electrocardiography and urinalysis were performed for all animals. Five animals in each group were sacrificed 1 and 30 days post treatment. The internal organs were subjected to histological evaluation.Results.The results of the study demonstrate that the treatment with low dose of LCTA-2034 does not produce any changes in majority of examined clinical-laboratory parameters with the exception of urinalysis revealed hematuria on day 1 post treatment. Microscopic pathology observation showed structure abnormalities of varying severity in liver, kidneys, heart, stomach, jejunum, ileum, spleen and thymus. Administration of high dose of LCTA-2034 caused mortality of 2 rats in group. The rest of the rats were observed a body weight lag, decrease of total leukocyte and erythrocyte count, hemoglobin and hematocrit level, relative weight of the thymus. Erythrocytes and nitrates were found in urine both on day 1 and on day 30 post treatment. In groups treated with high dose of the drug in addition to the listed above organs damage of the structure of lymph nodes, pancreas, ileum and brain was detected. Conclusion. Revealed toxic properties of LCTA-2034 depended on dose. Multiple administration of 1 therapeutic dose of the drug produces transient toxic effects completely reversible within 30 days. 


Author(s):  
Komail M. ◽  
Narendra Babu A.

The present study was undertaken to explore the nephroprotective potential of Jatrophacurcas fruit extracts against carbon tetrachloride (CCl4) induced nephrotoxicity in rats. Nephrotoxicity was induced by CCl4 (3ml/kg body weight) in animals. Blood biochemical parameters, urine analysis and histopathological studies were carried out to assess the nephroprotective effect. CCl4 administration induced significant nephrotoxicity in rats, which was evident from enhanced levels of albumin, potassium.From the obtained results it may be concluded that pretreatment of silymarin (50mg/kg dose orally) significantly reversed carbon tetrachloride induced nephrotoxicitywhere asJatrophacurcas methanol extract (250mg/kg body weight) showed significant effect against CCl4 induced nephrotoxicity in rats thanJatrophacurcas aqueous extract (p less than 0.001) for most of the blood biochemical parameters, hematological parameters as well in attenuation of pathological changes in kidney tissues.


2019 ◽  
Vol 86 (2) ◽  
pp. 14-21
Author(s):  
N.J. Andreychuk ◽  
L.І. Vlasyk

The safety of nanomaterials and nanotechnologies is an important factor in the regulation of industrial production and the introduction of nanoproducts into practice. The toxicological aspect of the use of silver nanoparticles (SNP) is insufficiently studied, leaving many questions without answer. The problem of dependence of toxicity on the shape and the size of nanoparticles is controversial and not well-studied, and there is a lack of research on the nanosilver effect on human and animal organisms. Objective. The aim of the work was to provide the hygienic assessment of harmful effects of silver nanoparticles of spherical and decahedron shape. Materials and Methods. Samples of solutions of spherical and decahedron SNP, synthesized by the method of photostimulated restoration, were intraperitoneally administered to white nonlinear rats both males and females aged 4 months. For the subacute toxicity study of spherical 45-nm nanosilver the animals were subdivided into three groups of (16 rats in each, 8 animals in a subgroup — according to gender). Every day they were injected with spherical SNP at doses of 0.1,1 and 5 mg/kg intraperitoneally for 14 days. The fourth group was the biological control. For the subacute toxicity study of decahedron 45-nm nanosilver the animals were subdivided into four groups (16 rats in each, 8 animals in the subgroup according to gender). The animals were injected intraperitoneally with 10, 5,1, and 0.1 mg/kg doses of SNP daily for 14 days. Fifth group was biological control. On 14th day animals were withdrawn from the experiment by decapitation under a slight, ethereal athetic. Results and Discussion. It was grounded the expediency of taking into account the physical and chemical properties of silver nanoparticles, including geometrical characteristics (shape, specific area of surface), the number of silver ions in nanoparticle and the quantity of nanoparticles in the solution while the determination of exposition of nanosilver or other nanochemicals of different geometric shapes. On models of subacute effect there were determined the peculiarities of different shapes nanosilver exposure and hygienic meaning of biochemical and pathomorphological changes as criteria of harmful effect. With the help of morphometric analysis of pathomorphological changes of internal organs of rats there was ascertained doserelated harmful effect of decahedron and spherical silver nanoparticles. As a result of the experiment, dose-dependent circulating swelling of the epithelium of convoluted tubules of the kidneys, hepatocytes, nuclei of cardiomyocytes, alteration of the epithelium of bronchi of different caliber, repletion of the blood vessels of the walls of the respiratory parts of the lungs, karyopicnosis of neurons of the cerebral cortex were observed. The revealed changes in the indices of prooxidant-antioxidant equilibrium, some biochemical indices and the changes in internal organs of animals testified to the less toxic effect of silver nanospheres in comparison with silver nanodecahedrons. Conclusions. 1. According to the analysis of the geometric characteristics of decahedron silver nanoparticles, it is established that the specific area of decaheders is 2 times bigger than the specific area of the spherical SNP, which provides twice bigger area of the contact of silver nanodecahedron in the biological environment. The decahedron nanoparticle contains 4.3 times less atoms than spherical, and, at the same mass concentration, a solution of nanosilver contains 4 times more silver nano decahedrons than spheres. 2. With the help of biochemical analyses of blood and liver tissue, as well as the morphometric analysis of pathological changes in the internal organs of laboratory rats, the dose-dependent harmful effect of silver nanoparticles of decahedral and, partially, spherical shape was established. The revealed changes in the blood and internal organs of animals testified to a less toxic effect of silver nanospheres in comparison with silver nanodecahedrons. 3. It was established that the differences in biochemical and pathomorphological changes in the internal organs of laboratory animals at the same dose of SNP the decahedron and spherical shape, calculated in mg/kg body weight, are related to a 4-multiple dose difference expressed in the ratio of «the number of nanoparticles/kg» of body weight and a 9-multiple difference in favor of nanodecahedrons while calculating the dose «specific surface area/kg» of body weight. Key Words: silver nanoparticles, silver nanodecahedron, silver nanosphere, toxicity, nanosilver.


2020 ◽  
Vol 65 (9-10) ◽  
pp. 13-20
Author(s):  
E. R. Pereverzeva ◽  
M. I. Treshchalin ◽  
I. D. Treshchalin

Relevance. Indications for rifabutin use are constantly expanding. It is used in the treatment of extremely complex nosological forms of infectious diseases. However, side effects of the medication, such as gastrointestinal toxicity and myelosuppression, in many cases do not allow the completion of treatment and weaken the patient-s adherence to therapy. This determines the need to find means to reduce the toxic properties of rifabutin.Objective. The aim of the study was to investigate the possibility of correction of gastrointestinal and hematological toxicity of rifabutin with ascorbigen.Material and Methods. The study was performed in male Wistar rats. The drugs were administered per os at therapeutic doses (50 mg/kg daily for 15 days). Ascorbigen was administered 30 minutes before rifabutin. Body weight dynamics, hematological parameters, blood biochemical parameters, electrocardiography, and urinalysis were performed for all animals during the study. Five animals in each group were euthanized on the 1st and 30th days after the end of the treatment course. The internal organs were subjected to histological evaluation.Results. It has been shown that combined treatment with rifabutin and ascorbigen leads to a weakening of the damaging effect of the antibiotic on the mucous membrane of the gastrointestinal tract and accelerates the processes of restoration of its structure. Clinically, this is expressed in the normalization of body weight gain of animals. The combined use of rifabutin with ascorbigen reduces the depth of cytopenia. The number of leukocytes in the peripheral blood of the rats was restored faster. There were no signs of atrophy of spleen-s lymphoid tissue. The administration of ascorbigen before rifabutin has a protective effect on the tissues of the kidneys and testes.Conclusion. Oral administration of ascorbigen 30 minutes before rifabutin significantly reduces the gastrointestinal toxicity and hematotoxicity of rifabutin and prevents the development of spermatogenesis disorders. This allows us to recommend it for combined use in order to improve tolerance to anti-TB treatment.


2015 ◽  
Vol 18 (1) ◽  
pp. 223-231 ◽  
Author(s):  
Ł. Zielonka ◽  
M. Gajęcka ◽  
M. Tarasiuk ◽  
M. Gajęcki

Abstract The aim of this study was to determine whether exposure to low doses of DON leads to changes in serum hematological and biochemical profiles. In the experiment, pre-pubertal gilts (with body weight of up to 25 kg) were administered DON per os at a daily dose of 12 μg/kg BW (group E, n=18) or a placebo (group C, n=21) over a period of 42 days. Blood for analysis was sampled seven times at weekly intervals. Minor, but statistically significant changes were observed in selected indicators, particularly in weeks 2 and 3 in values of biochemical parameters such AlAT, AspAT, Pin and Fe, and in values of hematological parameters such as RBC, MCV, MCHC, PLT, MPV, WBC, neutrophil, eosinophil, lymphocyte and monocyte counts. In group E, a decreasing trend of the values was observed in most cases, except for RBC, PLT, eosinophil, lymphocyte and monocyte counts. Similar results were obtained in the last two weeks of the experiment. Initially, exposure to DON has a stimulating effect, which is eliminated when adaptive mechanisms are triggered. The results of the study indicate that the intensity of biotransformation processes varies subjected to the body's energy resources.


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