Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease

The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a significant rise in Alkaline Phosphatases (ALP), bilirubin, white blood cells (WBC), and lymphocyte levels with a decrease in platelet count. Furthermore, the reduction in urea, uric acid, and aspartate transaminase (AST) levels and an increase in total protein levels were measured in subacute toxicity. SF1 increased spermatogenesis at 5 and 10 mg/kg doses. Teratogenicity study depicted no resorptions, early abortions, cleft palate, spina bifida and any skeletal abnormalities in the fetuses. Oxidative stress markers (Superoxide dismutase (SOD), Catalase (CAT), and glutathione (GSH) were increased in all the experiments, whereas the effect on melanoaldehyde Malondialdehyde (MDA) levels was variable. Histopathology further corroborated these results with no change in the architectures of selected organs. Consequently, a 2000 mg/kg dose of SF1 tends to induce minor liver dysfunction along with immunomodulation, and it is well below its LD50. Moreover, it can be safely used in pregnancy owing to its no detectable teratogenicity.

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RED CELL STROMA IN DOGS

Journal of Experimental Medicine ◽

10.1084/jem.102.6.705 ◽

1955 ◽

Vol 102 (6) ◽

pp. 705-711 ◽

Cited By ~ 2

Author(s):

F. S. Robscheit-Robbins ◽

G. H. Whipple

Keyword(s):

Blood Loss ◽

Hemolytic Anemia ◽

Protein Level ◽

Blood Cells ◽

Subcutaneous Injection ◽

Significant Rise ◽

Cell Regeneration ◽

Red Cell ◽

Protein Levels ◽

Very High

Normal red blood cells in dogs contain stroma in fairly uniform amounts. This red cell stroma is rich in proteins and lipides. Anemia due to blood loss causes an increase in stroma protein. The highest levels of stroma protein are found in the severe anemias. As the anemia is corrected by red cell regeneration, the stroma protein level falls to normal. Anemia due to blood destruction (phenylhydrazine) presents very high levels of stroma protein—almost double the increase noted in anemia due to blood loss. Hypoproteinemia added to anemia due to blood loss causes no significant change on the stroma protein level. Abscesses due to the subcutaneous injection of turpentine during the anemia cause slight decreases in the stroma protein levels. Chloroform poisoning has no effect on the stroma protein levels. The total lipides of the stroma are rather stable and are little influenced by anemia. In certain experiments with hemolytic anemia and with hypoproteinemia, there is a significant rise in total lipide figures.

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Abstract MP243: Detection Of Mesenchymal Stem Cells In Mobilized Autologous Peripheral Blood Transplantation From Patients With Ischemic Heart Disease

Circulation Research ◽

10.1161/res.129.suppl_1.mp243 ◽

2021 ◽

Vol 129 (Suppl_1) ◽

Author(s):

Hadyanto Lim ◽

Umar Zein ◽

Ilham Hariaji

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Heart Disease ◽

Ischemic Heart Disease ◽

Peripheral Blood ◽

Autologous Transplantation ◽

White Blood Cells ◽

Significant Rise ◽

Ischemic Heart ◽

Post Transplantation

Background: Mesenchymal stem cells (MSCs) improve the cardiac function and remodeling in patients with ischemic heart disease. However, their presence in the circulating peripheral blood and post-transplantation has not been fully elucidated. We aimed to investigate the effects of intravenous transplantation of mobilized autologous peripheral blood on the number of MSCs in patients with ischemic heart disease. Methods: Granulocyte-colony stimulating factor (G-CSF, 5.0 μg/kg/day) was given subcutaneously once a day for five days to 7 patients (4 women and 3 men, aged 54-69 years) with ischemic heart disease. Leukapheresis procedure was started on the day 5 of G-CSF using the Spectra Optia cell separator. Circulating and intravenous transplantation of autologous MSCs after leukapheresis were analyzed by flow cytometry. MSCs were identified on the basis of dual positive cells (CD73 + /CD105 + or CD90 + /CD73 + or CD90 + /CD105 + ) and detected as MSCs if a cluster of at least 10 cells could be found. Results: MSCs in the circulating peripheral blood and after transplantation were detected in 2 (28%) and 6 (85%) patients, respectively. The frequency of intravenous peripheral blood MSCs increased significantly after transplantation (from 32.57 ± 22.76 x10 -4 % to 58.57 ± 28.49 x 10 -4 % , p<0.001). Moreover, there were significant rise in the total white blood cells count (from 10.25 ± 4.86 x 10 3 /μl to 35.81 ± 7.07 x 10 3 /μl, p<0.001) and the levels of CD34 + cells (from 1.17 ± 0.93 cells/μL to 138.30 ± 11.26 cells/μL, p<0.001) after the infusion. Conclusions: The results show that intravenous transplantation of mobilized autologous peripheral blood increases the number of MSCs in patients with ischemic heart disease. Leukapheresis product of peripheral blood MSCs could therefore be a potential source for autologous transplantation in ischemic heart disease.

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Acute and Subacute Toxicity Evaluation of Corn Silk Extract

Preventive Nutrition and Food Science ◽

10.3746/pnf.2018.23.1.70 ◽

2018 ◽

Vol 23 (1) ◽

pp. 70-76 ◽

Cited By ~ 8

Author(s):

Ae Wha Ha ◽

Hyeon Jung Kang ◽

Sun Lim Kim ◽

Myung Hwan Kim ◽

Woo Kyoung Kim

Keyword(s):

Toxicity Evaluation ◽

Corn Silk ◽

Subacute Toxicity

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Plasma proprotein convertase subtilisin kexin type 9 is a heritable trait of familial combined hyperlipidaemia

Clinical Science ◽

10.1042/cs20110129 ◽

2011 ◽

Vol 121 (9) ◽

pp. 397-403 ◽

Cited By ~ 12

Author(s):

Martijn C.G.J. Brouwers ◽

Marleen M.J. van Greevenbroek ◽

Jason S. Troutt ◽

Angela Bonner Freeman ◽

Ake Lu ◽

...

Keyword(s):

Apolipoprotein B ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Significant Rise ◽

Low Density ◽

Proprotein Convertase ◽

Once Daily ◽

Heritable Trait ◽

The Relationship

The aim of the present study was to investigate the relationship between circulating PCSK9 (proprotein convertase subtilisin kexin type 9) and FCHL (familial combined hyperlipidaemia) and, when positive, to determine the strength of its heritability. Plasma PCSK9 levels were measured in FCHL patients (n=45), NL (normolipidaemic) relatives (n=139) and their spouses (n=72). In addition, 11 FCHL patients were treated with atorvastatin to study the response in PCSK9 levels. PCSK9 levels were higher in FCHL patients compared with NL relatives and spouses: 96.1 compared with 78.7 and 82.0 ng/ml (P=0.004 and P=0.002 respectively). PCSK9 was significantly associated with both TAG (triacylglycerol) and apolipoprotein B levels (P<0.001). The latter relationship was accounted for by LDL (low-density lipoprotein)–apolipoprotein B (r=0.31, P=0.02), not by VLDL (very-low-density lipoprotein)–apolipoprotein B (r=0.09, P=0.49) in a subgroup of subjects (n=59). Heritability calculations for PCSK9 using SOLAR and FCOR software yielded estimates of 67–84% respectively (P<0.0001). PCSK9 increased from 122 to 150 ng/ml in 11 FCHL patients treated with atorvastatin (40 mg) once daily for 8 weeks (P=0.018). In conclusion, plasma PCSK9 is a heritable trait associated with both FCHL diagnostic hallmarks. These results, combined with the significant rise in PCSK9 levels after statin therapy, warrant further studies in order to unravel the exact role of PCSK9 in the pathogenesis and treatment of this highly prevalent genetic dyslipidaemia.

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Effects of static magnetic field exposure on hematological and biochemical parameters in rats

Brazilian Archives of Biology and Technology ◽

10.1590/s1516-89132006000700005 ◽

2006 ◽

Vol 49 (6) ◽

pp. 889-895 ◽

Cited By ~ 12

Author(s):

Salem Amara ◽

Hafedh Abdelmelek ◽

Mohamed Ben Salem ◽

Rached Abidi ◽

Mohsen Sakly

Keyword(s):

Magnetic Field ◽

Static Magnetic Field ◽

Growth Rates ◽

Glucose Concentration ◽

Blood Cells ◽

White Blood Cells ◽

Male Rats ◽

Field Exposure ◽

Protein Levels ◽

Hematological And Biochemical Parameters

The present work was undertaken in order to investigate the effects of static magnetic field (SMF) on growth rates, hematopoiesis, plasmatic proteins levels, glucose concentration, lactate dehydrogenase (LDH) and transaminases activities in male rats. Sub-acute exposure of rats during 5 consecutive days to SMF (1h/day at 128mT) induced an increase of plasma LDH activity (+38%, p<0.05), and glucose concentration (+31%, p<0.05), whereas haematological parameters, protein levels, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities remained unchanged. SMF exposure of rats during 30 consecutive days (1hour/day at 128mT) decreased significantly growth rates by the second week and increased significantly the plasmatic total protein levels (+62%, p<0.05), hemoglobin (+10%, p<0.05), red blood cells (+7%, p<0.05), white blood cells (+17%, p<0.05), and platelet number (+10%, p<0.05). Sub-chronic exposure to SMF increased also LDH (+43%, p<0.05), AST (+ 41%, p<0.05) and ALT activities (+95%, p<0.05). In contrast, the glucose concentration was unaffected. These changes suggested that exposure to SMF had a possible effect on the proliferation of blood cells and enzymes release within blood indicating tissue alterations.

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Influence of Dietary Protein Levels on the Subacute Toxicity of Methylmercury in Mice (Proceedings of the 20th Symposium on Toxicology and Environmental Health)

Eisei kagaku ◽

10.1248/jhs1956.41.p21 ◽

1995 ◽

Vol 41 (1) ◽

pp. P21-P21

Author(s):

TATSUMI ADACHI ◽

AKIRA YASUTAKE ◽

KIMIKO HIRAYAMA

Keyword(s):

Environmental Health ◽

Dietary Protein ◽

Protein Levels ◽

Subacute Toxicity

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Relationship between mean platelet volume-to-lymphocyte ratio and coronary artery abnormalities in Kawasaki disease

Cardiology in the Young ◽

10.1017/s1047951118000422 ◽

2018 ◽

Vol 28 (6) ◽

pp. 832-836 ◽

Cited By ~ 2

Author(s):

Gulcin Bozlu ◽

Derya Karpuz ◽

Olgu Hallioglu ◽

Selma Unal ◽

Necdet Kuyucu

Keyword(s):

Coronary Artery ◽

Kawasaki Disease ◽

Mean Platelet Volume ◽

Characteristic Curve ◽

White Blood Cells ◽

Platelet Volume ◽

Distribution Width ◽

Coronary Artery Abnormalities ◽

Lymphocyte Ratio ◽

Protein Levels

AbstractObjectivesRecently, mean platelet volume-to-lymphocyte ratio has emerged as a novel parameter of inflammation. No study has investigated the role of mean platelet volume-to-lymphocyte ratio in children with Kawasaki disease. We aimed to evaluate the relationship between mean platelet volume-to-lymphocyte ratio and coronary artery abnormalities in Kawasaki disease.MethodsBetween January 2008 and January 2017, a total of 58 children with Kawasaki disease and 42 healthy subjects matched for sex and age were enrolled. Before the treatment, transthoracic echocardiography for all children was performed. Clinical and laboratory results including mean platelet volume, platelet distribution width, red blood cell distribution width, and counts of platelets, neutrophils, lymphocytes, and white blood cells, erythrocyte sedimentation rate, and C-reactive protein levels were measured. Mean platelet volume-to-lymphocyte ratio was calculated as mean platelet volume divided by lymphocyte count.ResultsCompared with healthy controls, mean platelet volume-to-lymphocyte ratio was significantly lower in the children with Kawasaki disease (p<0.01). A total of 14 patients (24.1%) had incomplete Kawasaki disease and 15 (25.8%) children with Kawasaki disease had coronary involvement. Mean platelet volume-to-lymphocyte ratio was significantly lower in patients with coronary artery abnormalities (p<0.01). According to receiver operating characteristic curve analysis performed for the prediction of coronary artery abnormalities, the best cut-off point for mean platelet volume-to-lymphocyte ratio was 2.5 (area under curve=0.593, sensitivity 53.3%, specificity 51.1%).ConclusionIt was first shown that the children with Kawasaki disease have lower mean platelet volume-to-lymphocyte ratio compared with control subjects. Mean platelet volume-to-lymphocyte ratio may be helpful in predicting coronary artery lesions in patients with Kawasaki disease.

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A subacute toxicity evaluation of green tea (Camellia sinensis) extract in mice

Food and Chemical Toxicology ◽

10.1016/j.fct.2011.07.007 ◽

2011 ◽

Vol 49 (10) ◽

pp. 2624-2630 ◽

Cited By ~ 33

Author(s):

Yu-Wen Hsu ◽

Chia-Fang Tsai ◽

Wen-Kang Chen ◽

Chun-Fa Huang ◽

Cheng-Chieh Yen

Keyword(s):

Green Tea ◽

Camellia Sinensis ◽

Toxicity Evaluation ◽

Subacute Toxicity

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Neuromodulatory Effects of Hesperidin in Mitigating Oxidative Stress in Streptozotocin Induced Diabetes

BioMed Research International ◽

10.1155/2014/249031 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 28

Author(s):

Mohammad Ashafaq ◽

Laxmi Varshney ◽

Mohammad Haaris Ajmal Khan ◽

Mohd. Salman ◽

Mehar Naseem ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Diabetic Rat ◽

Limiting Factor ◽

Enzymatic Antioxidants ◽

Neuroprotective Effects ◽

Once Daily ◽

Stress Markers ◽

Streptozotocin Induced Diabetes ◽

Nonenzymatic Antioxidants

Oxidative stress has been implicated in pathogenesis of streptozotocin- (STZ-) induced diabetes mellitus and its complication in central nervous system (CNS). Recent studies have provided insights on antioxidants and their emergence as potential therapeutic and nutraceutical. The present study examined the hypothesis that hesperidin (HP) ameliorates oxidative stress and may be a limiting factor in the extent of CNS complication following diabetes. To test this hypothesis rats were divided into four groups: control, diabetic, diabetic-HP treated, and vehicle for HP treatment group. Diabetes mellitus was induced by a single injection of STZ (65 mg/kg body weight). Three days after STZ injection, HP was given (50 mg/kg b.wt. orally) once daily for four weeks. The results of the present investigation suggest that the significant elevated levels of oxidative stress markers were observed in STZ-treated animals, whereas significant depletion in the activity of nonenzymatic antioxidants and enzymatic antioxidants was witnessed in diabetic rat brain. Neurotoxicity biomarker activity was also altered significantly. HP treatment significantly attenuated the altered levels of oxidative stress and neurotoxicity biomarkers. Our results demonstrate that HP exhibits potent antioxidant and neuroprotective effects on the brain tissue against the diabetic oxidative damage in STZ-induced rodent model.

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