scholarly journals The assessment of the toxicity of nanocomplexes containing gadolinium orthovanadate nanoparticles and cholesterol

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
A. Goltsev ◽  
◽  
M. Bondarovych ◽  
N. Babenko ◽  
Yu. Gaevska ◽  
...  

Nanocomplexes (NCs) synthesized at the Institute for Scintillation Materials of the National Academy of Sciences of Ukraine, consisting of nanoparticles (NPs) of gadolinium orthovanadate and cholesterol, are promising compounds that can be used as probes and fluorescent labels for tumor cells or experimental oncopathology treatment. However, the biosafety of such substances remains unclear. The purpose of the study was to evaluate the acute toxic effect of nanocomplexes on the healthy mice. Materials and methods. Nanocomplexes containing nanoparticles of GdYVO4:Eu3+ and cholesterol in 5 % glucose solution were administered to BALB/c mice once intraperitoneally in volumes of 0.1 mL, 0.5 mL, 1 mL, 2 mL, which corresponds to 5.9-6, 5 mg, 29.5-32.5 mg, 59.1-65.0 mg, 118.2-130.0 mg/kg body weight. Control animals were injected with the same volumes of 5 % glucose solution. On the 14th day, the morphological characteristics of organs, the number of CD34+CD38– cells among bone marrow total nucleated cells, the activity of gamma-glutamyl transferase (GGT) and glucose-6-phosphate dehydrogenase (G6PD) in liver homogenates were determined. Results. With the administration of NPs at a dose of less than 118.2 mg/kg body weight, no fatalities and symptoms of intoxication were showed, but there was a dose-dependent increase in the content of GGT in the liver of experimental animals. The use of NPs at a dose of 118.2-130.0 mg/kg body weight resulted in the death of 50 % of the animals on the 3rd day. In this group, on the 14th day, there were neoplasms in the spleen of one of the surviving animals, a decrease in the number of bone marrow total nucleated cell on the background of increased hematopoietic stem cells with CD34+CD38– phenotype, necrotic and dystrophic changes in the liver, and decreased activity of the G6PD enzyme. Conclusions. The potential median lethal dose of gadolinium orthovanadate nanoparticles and cholesterol in nanocomplexes was determined, which was 118.2-130.0 mg/kg animal body weight, which allows to classify them as low-toxic substances.

2020 ◽  
Vol 9 (8) ◽  
pp. e74985242
Author(s):  
Jalceyr Pessoa Figueiredo Junior ◽  
Fernando Guilherme Perazzo Costa ◽  
Ricardo Romão Guerra ◽  
Marcelo Helder Medeiros Santana ◽  
Matheus Ramalho de Lima ◽  
...  

The aim of this study was was to determine the nutritional requirements of digestible methionine+cystine (M+C) for white-egg layers aged one to six weeks. A completely randomized design with five methionine+cystine levels, six replicates, and 30 birds per experimental unit was adopted. Dietary treatments consisted of five diets supplemented with DL-Methionine with resulted in five levels of digestible methionine + cystine, 80% (0.516%), 90% (0.578%), 100% (0.640%), 110% (0.702%), and 120% (0.764%), based on Brazilian tables of nutritional requirements. Performance, serological blood, and histological data were evaluated. Feed intake, feed conversion, hepatic glycogen deposition, enzymatic activity of alanine aminotransferase and gamma-glutamyl transferase, and serum creatinine and albumin levels had showed a quadratic response to the levels of digestible M+C, with the respective requirements: 89.78% (0.575%), 114.33% (0.732%), 86.50% (0.554%), 100% (0.640%), 100.40% (0.643%), 104.30% (0.668%), and 111.88% (0.716%). Increasing levels of methionine+cystine elevated the relative liver weight and the deposition of hepatic glycogen, in addition to promote higher growth in pullets, with better body weight and body weight gain and feed conversion ratio. Our findings suggest that 0.732% digestible methionine+cystine is recommended, which corresponds to an intake of 151.20 mg/bird/d and a Met+Cys:Lys  ratio 83%, for light pullets from one to six weeks.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4822-4822
Author(s):  
Kavitha Siva ◽  
Pekka Jaako ◽  
Kenichi Miharada ◽  
Emma Rörby ◽  
Mats Ehinger ◽  
...  

Abstract Abstract 4822 Hematopoiesis is a complex process where a limited number of stem cells give rise to all mature blood cells. It involves interplay of several factors, many of which are yet to be identified. In a search for novel regulators of hematopoiesis, we chose to study SPARC (Secreted Protein Acidic and Rich in Cysteine, also known as Osteonection and BM40) because it is downregulated upon hematopoietic differentiation (Bruno et al., Mol Cell Biol, 2004) and might therefore play a role in the regulation of hematopoietic stem cells (HSC). SPARC is a matricellular protein that forms a major component of bone and is ubiquitously expressed in a variety of tissues. It is the founding member of a family of SPARC-like proteins. Several publications have indicated an important role for SPARC in hematopoiesis. In particular – knockdown of SPARC in zebrafish embryos resulted in an altered number of circulating blood cells, and a knockout mouse model showed thrombocytopenia and reduced erythroid colony formation. We carried out an in depth phenotypic and functional analysis of the hematopoietic system of SPARC knockout mice; using it as a model to gain insight into the role of SPARC in hematopoiesis. These mice are viable and fertile but show severe osteopenia and age-onset cataract at about six months of age. They also show an altered response to tumour growth and wound healing. We used mice (129SVJ background) (Gilmour et al. EMBO, 1998) that were less than six months old. These mice had normal peripheral blood counts and the bone marrow and spleen showed no alterations in morphology or cellularity. A detailed phenotypic analysis of precursors within the bone marrow showed no significant differences in myelo-erythroid precursors as compared to wild types (n=6). Though in vitro, the precursors showed lower ability to form BFU-E (n=5, p=0.048). In transplantations of lethally irradiated recipient mice, SPARC knockout cells gave rise to multi-lineage long-term reconstitution. Also, when competed with wild type cells, they provided reconstitution as well as their wild type counterparts. When SPARC knockout mice (n=8) were transplanted with wild type cells, there was normal reconstitution, indicating that a SPARC deficient niche can fully support normal hematopoiesis. We also tested if SPARC deficient mice respond differently to hematopoietic stress. We subjected mice (n=7) to sub lethal dose of irradiation and to experimentally induced anemia (n=7) and followed recovery by analyzing peripheral blood counts. In both SPARC knockouts and wild type mice, the blood counts recovered in a similar fashion. In conclusion, we find that SPARC is dispensable for murine hematopoiesis. It is possible that there are compensatory mechanisms involving other members of the SPARC family that ultimately lead to normal hematopoiesis in the murine model. In humans, SPARC maps to the deleted region in 5q MDS and has been reported to be 71 % down regulated in patient samples (Lehmann et al. Leukemia, 2007). It is the most prominent gene that is up regulated in response to lenalidomide, a drug that inhibits the malignant clone (Pellagatti et al. PNAS, 2007). SPARC is thus increasingly speculated to be involved in the pathophysiology of this hematopoetic disease. We analysed the expression levels of SPARC mRNA in the hematopoietic stem/progenitor cell compartment and found high expression levels in the CD34+ fraction of human cord blood cells. In contrast, there is very low level of SPARC expression in all compartments of murine HSCs. Therefore SPARC function may play a more important role in human hematopoiesis than in murine blood cell regulation. Disclosures: No relevant conflicts of interest to declare.


Sangyo Igaku ◽  
1993 ◽  
Vol 35 (1) ◽  
pp. 36-37
Author(s):  
Yutaka TAKASHIMA ◽  
Takashi AKAMATSU ◽  
Yasuhide ORIDO ◽  
Takaaki KINOUE

Author(s):  
O. G. Dawodu ◽  
O. A. T. Ebuehi ◽  
O. S. Odesanmi ◽  
M. O. Olalekan

Animal model development of alcohol administration in rats is of crucial importance as it gives indirect information to effects of alcohol in humans. An indirect assessment of this would be the biochemical and histological data that could arise from such experiments. 20 Male Wistar rats weighing (63.50±3.79 g), were divided into four groups (consisting 15 treated animals and 5 control animals) and administered with varying concentrations of ethanol (5% 15% and 40%) via intragastric intubation for a period of 28 days. Probic evaluations, liver biochemical enzymes and alteration in histology profile of gastrointestinal tract (GIT) and viscera organs (namely the liver, kidney, heart and lungs) were determined after experimental duration. At 40% ethanol administration, the rats showed biochemically significant decrease in serum gamma glutamyl transferase (GGT), serum aspartate (AST) and Alanine amino transferase (ALT) when compared to normal study while 5% and 15% ethanol administered rats were comparable with control values i.e. normal study. Probic evaluations such as body weight, water intake and food intake showed percentage decrease in 40% ethanol administrated rat when compared with controls. The photomicrographs of the 5% and 15% ethanol administered rats indicated mild damage in their histological profiles when compared to the normal study while there was more adverse damage occurring in the 40% ethanol administrated rats. Conclusion: From this study, serum aspartate (AST), gamma glutamyl transferase (GGT) and Alanine amino transferase (ALT), probic evaluation (body weight, food intake and water intake) coupled with histopathological investigation may be used as biomarker for the early diagnosis of ethanol toxicity in human beings.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5805-5805
Author(s):  
Lukun Zhou ◽  
Shuang Liu ◽  
Chuanyi M. Lu ◽  
Jianfeng Yao ◽  
Yuyan Shen ◽  
...  

Abstract Liver injury associated with veno-occlusive disease and graft-versus-host disease (GVHD) is a frequent and severe complication of hematopoietic stem cell transplantation, and remains an important cause of transplant-related mortality. Bone marrow derived mesenchymal stem cells (MSCs) have been evaluated for the prevention and treatment of refractory GVHD. However, poor cell viability has limited the therapeutic capacity of mesenchymal stromal cell therapy in vivo. In this study, we genetically engineered C57BL/6 mouse bone marrow MSCs using ex vivo retroviral transduction to overexpress Akt1, a serine threonine kinase and pro-survival signal protein, and tested the hypothesis that Akt1-expressing MSCs (Akt1-MSCs) are more resistant to apoptosis and can ameliorate acute liver injury induced by concanavalin A (ConA) in BALB/c mice. Cell proliferation and apoptosis analyses showed that, under both regular culture and high concentration IFN-γ (100 ng/mL) stimulation conditions, Akt1-GFP-MSCs had proliferation and survival (anti-apoptotic) advantages with down-regulated apoptosis pathways, compared to control GFP-MSCs. Twenty-four hours after receiving lethal dose of ConA (40 mg/kg, intravenous) (N=10 each group), no mouse survived, with or without 1x106 Akt1-MSCs or GFP-MSCs administration (intravenous); however, 3 and 1 survived in the 5×106 Akt1-MSCs group and 5×106 GFP-MSCs groups, respectively. In subsequent sub-lethal dose ConA (20 mg/kg) experiments, compared to GFP-MSCs, mice received Akt1-MSCs administration had significantly lower serum AST, ALT, TNF-α and IFN-γ levels and less histopathological abnormalities. In addition, Akt1-MSCs treated mice had significantly higher serum concentrations of IL-10, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). In vivo imaging showed that, hepatic fluorescence signal in sub-lethal ConA+Akt1-MSCs group was significantly stronger than ConA+GFP-MSCs group on day 0, and persisted up to 14 days, whereas the signal in ConA+GFP-MSCs, Akt1-MSCs and GFP-MSCs groups was negligible on both day 7 and day 14. Thus, bone marrow derived MSCs genetically enhanced with Akt1 had survival advantage in vitro and in vivo, and have the potential to be a potent therapy for prevention and amelioration of GVHD-associated liver impairment. Further translational pre-clinical studies are ongoing to further determine the efficacy, dosage and timing of administration of Akt1-MSCs in animal models. Disclosures No relevant conflicts of interest to declare.


2009 ◽  
Vol 28 (9) ◽  
pp. 591-598 ◽  
Author(s):  
MT Yakubu ◽  
BB Bukoye ◽  
AT Oladiji ◽  
MA Akanji

Aqueous extract of Bambusa vulgaris L. leaves at 250 and 500 mg/kg body weight was investigated for toxic effects in pregnant rabbits. Apparently healthy, female rabbits (Dutch) weighing between 1.62 and 1.70 kg as previously used in our abortifacient study were paired overnight with male rabbits in ratio 2:1 and those that became pregnant were completely randomized into three groups (A-C). Group A (the control), received orally 1.85 mL/kg body weight (3 mL) of distilled water thrice daily on days 1-9 of pregnancy while groups B and C were treated orally with the same volume corresponding to 250 and 500 mg/kg body weight of the extract. Clinical signs of toxicity were not observed in all the animals during the study. The extract did not significantly alter (p > .05) the serum follicle stimulating hormone and total protein content of the pregnant rabbits throughout the exposure period whereas, the concentrations of luteinizing hormone, progesterone, albumin, globulin, urea and calcium decreased in the serum of the rabbits. At 250 mg/kg body weight, the extract increased kidney alkaline phosphatase (ALP) activity whereas at 500 mg/kg body weight of the extract, the ALP level was similar to the control group. Liver ALP at all doses, as well as the activity of gamma glutamyl transferase (GGT) at 500 mg/kg body weight was reduced. This reduction was accompanied by an increase in serum ALP and GGT at these doses. At 250 mg/kg, the extract increased kidney GGT. Conversely, at 500 mg/ kg, kidney GGT activity decreased. Liver and serum GGT were not altered by the 250 mg/kg. The extract also increased the serum levels of creatinine, uric acid, sodium, potassium and bicarbonate ions as well as total and conjugated bilirubin. In the hepatocytes of extract-treated animals, there was no evidence of necrosis, inflammation, fibrosis and degenerative changes in the central vein and radiating hepatic cords, while the glomerulus and the tubules of the nephrons also remained intact. The alterations in biochemical parameters by the aqueous extract of B. vulgaris leaves suggests adverse effect on the synthetic, secretory, reabsorptive and excretory functions of liver and kidney of the animals. Therefore, the absence of histopathological lesions in the hepatocytes and nephrons implies that histopathological changes are not a sensitive assay for the assessment of tissue damage by the extract.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Nor Aziyah Mat-Rahim ◽  
Tong-Hye Lim ◽  
Nur-Asyura Nor-Amdan ◽  
Sazaly AbuBakar

Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08) were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA). These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM) proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x) and level of GGT (more than 2x) in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver.


In the course of investigations on the production, distribution, and rate of disappearance in the body of immune substances, we were occupied in 1908 and previous years with a series of experiments on agglutinins, and we arrived at conclusions pointing to their close relationship to the blood and blood-forming organs (1, 2). In association with these inquiries, one of us (G. D.), together with W. Ray, published a communication on the relation­ship between the blood volume and the distribution of agglutinins within the circulation (3). It was there shown that the concentration of this substance (agglutinin) in the blood after inoculation into an animal was proportional to the body surface of the animal concerned, and was thus approximately proportional to the two-thirds power of the weight. Hence was deduced the conclusion that the blood volume of the animals examined was proportional to their body surface.


2016 ◽  
Vol 4 (2) ◽  
pp. 178 ◽  
Author(s):  
Mona Abdel Rasoul ◽  
Gehan Marei

This study aimed to investigate the prophylactic effect of turmeric (Curcuma longa) Rhizome Ethanolic extract (CLRE) at 250 mg/kg as antioxidant effects against penconazole induced sub-acute toxicity. Hepatic, renal and testicular pathological changes caused by oxidative damage induced by penconazole in rats were biochemically and histologically evaluated. Male rats were treated with penconazole, via oral route, at doses of 0.5 mg/ kg body weight (b.w.; acute reference dose, ARfD), 25 mg/kg b.w. (no observed adverse effects level, NOAEL) and 100 mg/ kg b.w. (1/20 lethal dose [LD50]) for 28 consecutive days. Penconazole treatments had significant (p < 0.05) and gradual reductions in body and relative testicular weight accompanied by significant elevation in the relative liver and kidney weights. Significant increase serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dhydrogenase(LDH), gamma-glutamyl transferase (GGT), creatinine (Cre), uric acid and blood glucose was observed due to penconazole treatments. However, total protein and testosterone hormone were significantly decreased. Exposure to penconazole caused increase in lipid peroxidation (LPO) and decreased of liver and kidney antioxidant enzymes activity as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Histopathological studies confirmed the ameliorative beneficial effects of turmeric biochemical parameters. On the basis of this study, the use of tumeric rhizomes as a functional food or as a nutraceutical product could be a useful approach to protect individuals who are regularly exposed to penconazole.


2019 ◽  
Vol 79 (4) ◽  
pp. 629-638 ◽  
Author(s):  
K. K. Dar ◽  
S. Ali ◽  
M. Ejaz ◽  
S. Nasreen ◽  
N. Ashraf ◽  
...  

Abstract Background Hepatocellular carcinoma is the most frequent primary malignancy of liver and accounts for as many as one million deaths worldwide in a year. Objectives The aim of the present study was to evaluate the anti-cancerous efficiency of Bergenia ciliata rhizome against diethylnitrosoamine induced hepatocarcinogenesis in Balb C mice. Methods One percent diethylnitrosoamine was prepared by using 99 ml of normal saline NaCl (0.9 percent) solution to which was added 1 ml of concentrated diethylnitrosoamine (DEN) solution (0.01 μg/μl). Extract of Bergenia ciliata was prepared by maceration technique. Mice were classified into four groups as follows: Group 1 a control group (N=7) received saline solution (3.5 μl/mg), group 2 (N=14) received diethylnitrosoamine (3.5 μl/mg) intraperitoneally once in a week for eight consecutive weeks, group 3 (N=7) received plant extract (150 mg/kg (Body weight)) once in a week, while group 4 (N=7) was given combination of diethylnitrosoamine (3.5 μl/mg) and plant extract (150 mg/kg (Body weight)). After eight weeks of DEN induction group 2 mice were divided into two subgroups containing seven mice each, subgroup 1 was sacrificed while subgroup 2 was treated with plant extract (150 mg/kg (Body weight)) once in a week for eight consecutive weeks. Results The model of DEN injected hepatocellular carcinomic (HCC) mice elicited significant decline in levels of albumin with concomitant significant elevations in tumor markers aspartate aminotransferase, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. The intraperitoneal administration of B. ciliata as a protective agent, produced significant increase in albumin levels with significant decrease in the levels of tumor markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha feto protein (AFP), gamma glutamyl transferase (Y-GT), 5 nucleotidase (5NT), glucose-6-phosphate dehydrogenase (G6PDH) and bilirubin. Conclusion Bergenia ciliata has potent antioxidant activity, radical scavenging capacity and anticancerous properties. Bergenia ciliata extracts may provide a basis for development of anti-cancerous drug.


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