scholarly journals Strain differences in toxicity of vitamin K antagonist warfarin in rats

2013 ◽  
Vol 78 (3) ◽  
pp. 383-394 ◽  
Author(s):  
Jelena Djokic ◽  
Marina Ninkov ◽  
Aleksandra Popov-Aleksandrov ◽  
Ivana Mirkov ◽  
Vesna Subota ◽  
...  

Warfarin (4-hydroxy coumarin) is Vitamin K (VK) antagonist that inhibits Vitamin K-dependent (VKD) processes, such as blood coagulation. It exerts influence on some non-VKD-related activities as well. In this study, the effect of subacute (30-day) oral warfarin (2 mg L-1 and 1 mg L-1) intake on hematological parameters was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), that differ in their sensitivity to certain chemicals. Greater susceptibility to anticoagulant effect of 2 mg L-1 of warfarin was observed in AO rats and was associated with an increase in relevant hematological parameters in this strain. Although both strains responded to 2 mg L-1 of warfarin with quantitative changes in peripheral blood leukocytes differential bone marrow and lung responses were observed. Strain-related differences in proinflammatory activity of peripheral blood granulocytes and in mononuclear cell IFN-? production were observed. Recognition of differences in quantitative and qualitative effects of oral warfarin on processes other than hemostasis might be of relevance for those humans who are on warfarin therapy.

Author(s):  
T. V. Usenko ◽  
V. G. Shulyak

Introduction. Epoxiconazole is a highly effective triazole fungicide. It is a part of many modern compounds for the control of phytopathogens. Widely used in agriculture in all over the world and in Ukraine, in particular. Despite its hepatotoxic characteristics, this fungicide alters the hematological parameters of blood.The aim of the study – to investigate the effects of generic triazole fungicide epoxiconazole, 95% on hematological and cytochemical parameters of peripheral blood of Wistar Hannover rats in acute experiment.Research Methods. 10 healthy males of Wistar Han rats were equally divided into control (0 mg/kg/bw) and experimental groups. Dose 1580 mg/kg/bw of epoxiconazole (1/2 LD50) was administrated once orally by gavage to 5 experimental rats. Peripheral blood was studied at 0 and 1, 3, 7, 14 day after exposure (DAE). RBC, HGB, HCT, erytrocyte indices MCV, MCH, MCHC, WBC and PLT were, hemogram and morphological disturbances of cells were studied,percentage ratio of different types of leukocytes was calculated.The cytochemical status of leukocytes was assessed on the basis of determining the enzymatic activity of specific naphthol-AS-D-chloroacetateterase in neutrophils, succinate dehydrogenase and acid phosphatase in lymphocytes.Results and Discussion. Erythrocytosis in response to pesticide intoxication with a decrease of mean cellhemoglobin concentration in one erythrocyte; the reduction of hemoglobin concentration in the end of experiment against the background of active polychromasia confirmed the anemic effect of epoxiconazole. Reactive neutrophilia, stimulation of lymphocytopoiesis and monocytopoiesis, appearance of macrophages in the peripheral blood, increased activity of naphthol-AS-D-chloroacetateterase, succinate dehydrogenase and acid phosphatase were considered as compensatory mechanisms. Reverse quantitative changes in the ratio of lymphocytes subpopulations based on the activity of acid phosphatase were noted.Conclusions. Results of the study of generic fungicide epoxiconazole, 95% hematotoxic activity in the acute experiment on Wistar Hannover male rats showed the development of latent anemia, which was manifested in the late-term study; activation of monocytopoesis; increase of macrophages in the peripheral blood; changes in the immune response of the body and the appearance of atypical normocytes and lymphocytes with nuclear abnormalities.


2014 ◽  
Vol 17 (2) ◽  
pp. 263-273 ◽  
Author(s):  
J. Małaczewska

Abstract Silver nanoparticles, which have found a wide range of applications owing to their antimicrobial properties, are also recommended as dietary supplements in alternative medicine. Studies on rodents confirm that nanosilver is absorbed from the digestive tract into the bloodstream, which implies its possible interactions with leukocytes. The objective of the experiment discussed herein has been to determine the effect of 28-day oral administration of different doses (0.25, 2.5, 25 ppm) of commercial silver nanocolloid on hematological parameters, percentages of particular lymphocyte populations and activity of the peripheral blood leukocytes in mice. All the tested colloid doses decreased the counts of monocytes in the animals’ blood and induced phenotypic modifications among lymphocytes: an increase in CD4+/CD8+ T cell distribution, a decrease in NK and NKT cell distribution (doses of 0.25 and 2.5 ppm) and an increased CD4+:CD8+ ratio (25 ppm). Silver nanocolloid also affected the activity of cells, depressing the proliferation of lymphocytes (0.25 ppm) and stimulating phagocytosis as well as the respiratory burst of granulocytes and monocytes (all doses). The results verify the influence of orally administered silver colloid on the peripheral blood leukocytes, at the same time implying the potential risk of developing an inappropriate immune response of an organism exposed to prolonged administration of this substance


2018 ◽  
Vol 14 (66) ◽  
pp. 075
Author(s):  
H. S. Lavryk ◽  
O. P. Korniychuk ◽  
Z. Ya. Fedorovych ◽  
Z. D. Vorobets

2020 ◽  
Vol 86 (5) ◽  
pp. 480-485
Author(s):  
Lior Segev ◽  
Ilana Naboishchikov ◽  
Diana Kazanov ◽  
Ezra Bernstein ◽  
Meital Shaked ◽  
...  

Background CD24 is a sialoglycoprotein anchored to the cell surface via glycosylphosphatidylinositol and is involved in intracellular signaling processes. It plays an important role in the early stages of the multistep process of colorectal carcinogenesis. Several single nucleotide polymorphisms in the CD24 gene are reported to exert a diverse effect on cancer risk. We aimed to elucidate whether CD24 TG/del genetic variants are associated with susceptibility to colorectal cancer (CRC). Methods The study included 179 subjects, 36 with CRC (prior to surgery) and 143 healthy control subjects. Deoxyribonucleic acid was purified from peripheral blood leukocytes, and by using restriction fragment length polymorphism analysis, the CD24 gene was genotyped for the specific genetic variant, TG deletion. Additionally, CD24 protein expression levels were determined by Western blotting analysis. Results The incidence of the TG/del was higher among the CRC patients compared with healthy controls, 14% and 10%, respectively ( P = .54). CD24 protein levels were significantly higher among CRC patients. There were no significant differences in CD24 expression between CRC patients at different stages of the disease or between patients who carry the mutation and those who did not. Conclusions CD24 genetic variant might be of clinical value for risk assessment as part of cancer prevention programs. Further study on larger populations is needed to validate the importance of this dinucleotide deletion in CRC development. Overexpression of CD24 protein occurs early along the multistep process of CRC carcinogenesis, and a simple blood sample based on CD24 expression on peripheral blood leukocytes can contribute to early diagnosis.


2020 ◽  
Vol 33 (11) ◽  
pp. 1047-1047
Author(s):  
Wan-yue Liu ◽  
Yi Sun ◽  
Shu-na Huang ◽  
Yu-zhen Lin ◽  
Hong-yan Guo ◽  
...  

Abstract Background To investigate the main environmental factors of hypertension and the relationship between hypertension and circular RNAs in peripheral blood lymphocytes. Methods This was a case–control study. A total of 681 hypertension patients and 485 subjects without hypertension were recruited between April 2017 and October 2018. All participations completed the questionnaire investigation, physical examination, and laboratory detection. Quantitative real-time polymerase chain reaction was used to analyze circRNAs (hsa_circ_0001946 and hsa_circ_0125589) in peripheral blood leukocytes in 84 hypertensives and 84 controls. Multivariate logistic regression and crossover analysis were used to analyze the interaction and association between environmental factors and circRNAs in hypertension. Results After adjusted by gender, age and marital status, overweight/obesity (odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.24–2.22), abdominal obesity (OR = 2.17, 95% CI 1.54–3.04), anxiety (OR = 2.15, 95% CI 1.41–3.28), family history of hypertension (OR = 4.26, 95% CI 3.18–5.70), and higher levels of hsa_circ_0001946 (OR = 4.13, 95% CI 1.85–9.21) were risk factors for hypertension, while levels of hsa_circ_0125589 were not associated with hypertension. Crossover analysis showed that the risk of hypertension was 13.12 times higher (95% CI 3.89–44.23) in overweight subjects with high hsa_circ_0001946 levels compared with normal weight subjects with low hsa_circ_0001946 levels. Further, the risk of hypertension was 17.78 times higher (95% CI 1.88–168.61) in subjects with anxiety and high hsa_circ_0001946 levels. Conclusions Hypertension is the result of both environmental factors and genetic factors. Higher hsa_circ_0001946 levels, overweight and anxiety may increase the risk of hypertension, while hsa_circ_0125589 levels are not related to hypertension.


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