Hematotoxic Effects Research Articles

Clinical and Immune Effects of Peri-Transplantation JAK Inhibition for Myelofibrosis.

Despite the introduction of JAK inhibitors, allogeneic hematopoietic cell transplant remains the only potentially curative treatment for patients with myelofibrosis but has considerable treatment-related complications. Whether the incorporation of JAK inhibition into the transplant algorithm leads to improved outcomes is still unclear. Here, we analyzed different transplant platforms in myelofibrosis patients undergoing a first transplant, comparing immune profiles and outcomes of (1) 33 patients continuing JAK inhibition at start of conditioning until stable engraftment (PERI-group), (2) 38 patients receiving JAK inhibition prior to transplant until start of conditioning (PRE-group), and (3) 38 patients that had never received JAK inhibition (NON-group). Patients in the PERI-group showed significantly higher early B-cell recovery as well as significantly increased late recovery of gamma-delta T cells and NK cells. We observed excellent neutrophil and platelet engraftment (100% for both) in the PERI-group and no hematotoxic effects or increased rates of infections following peri-transplant JAK inhibition. Cumulative incidence of acute graft-versus-host disease (GvHD) grade II-IV at day 100 after transplant was 15% in the PERI-group versus 29% in the PRE-group versus 34% in the NON-group. Cumulative incidence of relapse at 1 year after transplant was 9% in the PERI-group compared with 16% in the PRE-group and 18% in the NON-group. In conclusion, peri-transplant JAK inhibition was feasible with promising engraftment and acute GvHD rates, though deserves further investigation.

Discovery of a Novel Macrocyclic Noncovalent CDK7 Inhibitor for Cancer Therapy.

Cyclin-dependent kinase 7 (CDK7) is a key regulator of the cell cycle and transcription, making it a promising target for cancer therapy. Although current CDK7 inhibitors have improved in their selectivity and druglike properties, CDK7 inhibitors have failed to progress through clinical development due to severe gastrointestinal and hematotoxic side effects. To mitigate these limitations, we have developed novel, macrocyclic, noncovalent CDK7 hit compounds 2 and 3 using a macrocyclization platform that has optimized these compounds from SY-5609, a leading clinical asset. We conducted extensive structure-activity relationship (SAR) studies to improve their potency, enhance oral bioavailability, and reduce intestinal distribution, which resulted in compound 13. Compound 13 exhibits potent in vitro activity, good ADME properties, and robust in vivo antitumor activity in xenograft models as a monotherapy. Notably, compound 13 with lower basicity demonstrated improved Caco-2 permeability, reduced blood/plasma ratio, and reduced intestinal distribution in rats, thus mitigating gastrointestinal and hematotoxic side effects.

Oxidative-Stress and Hematological Alterations Induced by the Egyptian Naja nubiae Venom in Rats

Background: Snake venoms have been the subject of intense studies to understand the mechanisms involved in toxicity. Limited information is available regarding the Egyptian Spitting Cobra’s oxidative stress and hematological profile (Naja nubiae). Objectives: The present study aimed to evaluate the oxidative stress produced by the venom of N. nubiae and determine its hematotoxic effects in rats. Methods: The adult male Albino rats (N=30) were subcutaneously (SC) injected with a physiological saline solution in the control group. The SC injection of snake venom in groups 2 and 3 was 1/4 and 1/2 of the LD50 (0.32 mg/kg and 0.65 mg/kg body weight, respectively). Blood samples were collected at 30, 120, and 360 minutes post-injection for biochemical and hematological assays in both control and treated groups. Levels of oxidative stress biomarkers, including lipid peroxidation (LPO), protein carbonyl content (PCC), and nitric oxide (NO) were estimated. Antioxidants agents comprising glutathione (GSH) level, activities of superoxide dismutase (SOD), and catalase (CAT) were also evaluated. Results: The results showed that the effects of snake venom on blood cells are dose-dependent. Furthermore, significant alterations (P≤0.05) were observed in the hemoglobin (Hb) concentration, packed cell volume (PCV), and the number of red blood cells (RBCs) in response to a low dose of venom at the 30-minute time. In contrast to the control group, the venom induced a substantial elevation in LPO, NO, and PCC levels, indicating a disturbance in redox equilibrium. Additionally, significant reductions were detected in the GSH levels as well as SOD and CAT activities in all treated groups. Conclusion: Overall, the cytotoxicity’s potential to induce oxidative stress may reduce its antioxidant systems, leading to redox disturbance and hematological alteration.

Integrative investigation of hematotoxic effects induced by low doses of lead, cadmium, mercury and arsenic mixture: In vivo and in silico approach

The effect of the lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As) mixture (MIX) on hematotoxicity development was investigated trough combined approach. In vivo subacute study (28 days) was performed on rats (5 per group): a control group and five groups orally exposed to increasing metal(loid) mixture doses, MIX 1- MIX 5 (mg/kg bw./day) (Pb: 0.003, 0.01, 0.1, 0.3, 1; Cd: 0.01, 0.03, 0.3, 0.9, 3; Hg: 0.0002, 0.0006, 0.006, 0.018, 0.06; As: 0.002, 0.006, 0.06, 0.18, 0.6). Blood was taken for analysis of hematological parameters and serum iron (Fe) analysis. MIX treatment increased thrombocyte/platelet count and MCHC and decreased Hb, HCT, MCV and MCH values compared to control, indicating the development of anemia and thrombocytosis. BMDIs with the narrowest width were identified for MCH [pg] (6.030E-03 - 1.287E-01 mg Pb/kg bw./day; 2.010E-02 - 4.290E-01 mg Cd/kg bw./day; 4.020E-04 - 8.580E-03 mg Hg/kg bw./day; 4.020E-03 - 8.580E-02 mg As/kg bw./day). In silico analysis showed target genes connected with MIX and the development of: anemia - ACHE, GSR, PARP1, TNF; thrombocytosis – JAK2, CALR, MPL, THPO; hematological diseases - FAS and ALAD. The main extracted pathways for anemia were related to apoptosis and oxidative stress; for thrombocytosis were signaling pathways of Jak-STAT and TPO. Changes in miRNAs and transcription factors enabled the mode of action (MoA) development based on the obtained results, contributing to mechanistic understanding and hematological risk related to MIX exposure.

Coniferyl ferulate alleviate xylene-caused hematopoietic stem and progenitor cell toxicity by Mgst2.

Xylene exposure is known to induce toxicity in hematopoietic stem and progenitor cells (HSPCs), leading to bone marrow suppression and potential leukemogenesis. However, research on the gene expression profiles associated with xylene-induced toxicity in HSPCs, and effective therapeutic interventions, remains scarce. In our study, we employed single-cell RNA sequencing to capture the transcriptomic shifts within bone marrow HSPCs both prior to and following treatment with coniferyl ferulate (CF) in a mouse model of xylene-induced hematotoxicity. Subsequently, we pinpointed CF as a targeted agent using SPR-LC/MS analysis. This enabled us to confirm the link between the gene Mgst2 and specific cellular subtypes. Our data revealed that CF significantly countered the reduction of both monocyte and neutrophil progenitor cells, which are commonly affected by xylene toxicity. Through targeted analysis, we identified Mgst2 as a direct molecular target of CF. Notably, Mgst2 is preferentially expressed in neutrophil progenitor cells and is implicated in mitochondrial metabolic processes. By selectively inhibiting Mgst2 in bone marrow, we observed amelioration of xylene-induced hematotoxic effects. In summary, our findings suggest that coniferyl ferulate can mitigate the detrimental impact of xylene on hematopoietic stem and progenitor cells by targeting Mgst2, particularly within subpopulations of neutrophil progenitors. This discovery not only advances our comprehension of the cellular response of HSPCs to xenobiotic stressors like xylene but also identifies CF and Mgst2 as potential therapeutic targets for alleviating xylene-induced hematotoxicity.

Ameliorative effect of Tinospora cordifolia stem aqueous extract on Hematological parameters of wistar rat against HgCl2 induced toxicity

Blood is crucial for the human body's health and survival. It carries out a variety of functions, including as delivering nutrients and oxygen. RBCs, WBCs, plasma, and platelets are the blood's major four constituents. It serves as a pathological sign for the condition of animals under different situations and toxicant exposure. This work aimed to explore the in vivo therapeutic mechanism of Tinospora cordifolia aqueous extracts against the haematotoxic effects of HgCl2. Ameliorative effect of T.cordifolia aqueous extract was evaluated in two groups of rats, including a treated group and a control group. The treated group was divided into following subgroups, I: HgCl2 treated, subgroup II: HgCl2 + T. cordifolia treated, subgroup III: T. cordifolia treated. These treated subgroups were further divided into 5 set of rats, one for acute (1d), three for sub-acute (7, 14 and 28ds), and one for sub-chronic (60 ds) study. The controls were run simultaneously. Male Wistar rats were given aqueous extracts of T. cordifolia (400 mg/kg body weight, orally, once daily) along with HgCl2 treatments. Dose of HgCl2 administered to animals after calculation of LD50 (25 mg/kg body weight). Animals used in acute, sub-acute, and sub-chronic studies of mercuric chloride received 1/10, 1/50, and 1/100 of the calculated LD50. This corresponds to 2.5, 0.5 and 0.25 mg/kg respectively. In mercury-treated mice, significant reductions in WBC, RBC, Hb, PCV and platelet count were also observed. These HgCl2-related effects were circumvented by regular intake of T. cordifolia aqueous extract. These results show that T. cordifolia protects against HgCl2 poisoning.

Mitigation of Benzene-Induced Haematotoxicity in Sprague Dawley Rats through Plant-Extract-Loaded Silica Nanobeads.

Benzene, a potent carcinogen, is known to cause acute myeloid leukaemia. While chemotherapy is commonly used for cancer treatment, its side effects have prompted scientists to explore natural products that can mitigate the haematotoxic effects induced by chemicals. One area of interest is nano-theragnostics, which aims to enhance the therapeutic potential of natural products. This study aimed to enhance the effects of methanolic extracts from Ocimum basilicum, Rosemarinus officinalis, and Thymus vulgaris by loading them onto silica nanobeads (SNBs) for targeted delivery to mitigate the benzene-induced haematotoxic effects. The SNBs, 48 nm in diameter, were prepared using a chemical method and were then loaded with the plant extracts. The plant-extract-loaded SNBs were then coated with carboxymethyl cellulose (CMC). The modified SNBs were characterized using various techniques such as scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-visible spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The developed plant-extract-loaded and CMC-modified SNBs were administered intravenously to benzene-exposed rats, and haematological and histopathological profiling was conducted. Rats exposed to benzene showed increased liver and spleen weight, which was mitigated by the plant-extract-loaded SNBs. The differential white blood cell (WBC) count was higher in rats with benzene-induced haematotoxicity, but this count decreased significantly in rats treated with plant-extract-loaded SNBs. Additionally, blast cells observed in benzene-exposed rats were not found in rats treated with plant-extract-loaded SNBs. The SNBs facilitated targeted drug delivery of the three selected medicinal herbs at low doses. These results suggest that SNBs have promising potential as targeted drug delivery agents to mitigate haematotoxic effects induced by benzene in rats.

Oxidative stress in animals exposed to cypermethrin: mechanisms of development and possible risks

The purpose of the study is to establish the mechanisms of development of oxidative stress during long-term low-dose exposure to cypermethrin on the animal organism and to substantiate possible risks. The work was carried out using Wistar rats, which were intragastrically injected daily with cypermethrin at a dose of 1/1000 LD50 for 60 and 120 days. At the same time, control animals received an appropriate volume of saline solution inside. When removing animals from the experiment, blood was taken to determine the number of red blood cells, the concentration of hemoglobin, glucose, lactic and uric acids, and total bilirubin. In the study of erythrocytes and liver, biochemical parameters characterizing carbohydrate and purine metabolism, processes of xenobiotics biotransformation, pro- and antioxidant processes were determined. Long-term lowdose exposure to cypermethrin for 60 days causes hematotoxic effects in animals, enhancement of xenobiotic biotransformation processes, and slight compensatory restructuring of metabolic processes in the liver. Exposure to 1/1000 LD50 of cypermethrin for 120 days, in addition to the above effects, causes the development of acidosis, enhances pro-oxidant processes, and suppresses the function of the antioxidant defense system and the pentose cycle. The decrease in the activity of the liver antioxidant system is due to glutathione deficiency due to the activation of xenobiotic biotransformation systems and suppression of the activity of glutathione reductase and glucose-6- phosphate dehydrogenase, which ultimately leads to the development of oxidative stress. Long-term exposure of animals to low doses of cypermethrin causes hemolysis of erythrocytes, lactic acidosis, activation of prooxidant systems, and inhibition of the antioxidant defense system. Deficiency of carbohydrates and suppression of the activity of the pentose cycle indicate a decrease in the functional activity of the liver and an increased risk of immunosuppression.

Individual modelling of haematotoxicity with NARX neural networks: A knowledge transfer approach

Cytotoxic cancer therapy often results in dose-limiting haematotoxic side effects. Predicting an individual's risk is a major objective in precision medicine of cancer treatment. In this regard, patient heterogeneity presents a significant challenge. In this paper, we explore the use of hypothesis-free machine learning models based on recurrent nonlinear auto-regressive networks with exogenous inputs (NARX) as an approach to achieve this goal. Also, we propose a knowledge transfer approach to ameliorate the issue of sparse individual data, which typically hampers learning of individual networks. We demonstrate the feasibility of our approach based on a virtual patient population generated using a semi-mechanistic model of haematopoiesis and imposing different cytotoxic therapy scenarios on it. Employing different techniques of model optimisation, we derive robust and parsimonious individual networks with good generalisation performances. Moreover, we analyse in detail possible factors influencing the generalisation performance. Results suggest that our transfer learning approach using NARX networks can provide robust predictions of individual patient's response to treatment. As a practical perspective, we apply our approach to individual time series data of two patients with non-Hodgkin's lymphoma.

Ameliorative Effects of Vitamins C and E on Haematotoxicity and Spleen Histopathology Induced by Dichlorvos Insecticide in Female Wistar Rats

This research aimed to assess the toxicological effects of dichlorvos insecticide (2,2-dichlorovinyl dimethyl phosphate or DDVP) on haematological indices of female Wistar rats and to investigate the antioxidant properties of vitamins C and E in ameliorating haematotoxicity. The rats were divided into 6 groups; control-water, control-oil, dichlorvos group, dichlorvos + vitamin C group, dichlorvos + vitamin E group and dichlorvos + vitamin C + E group. Dichlorvos and vitamins were orally administered to rats with an interval of half an hour between treatments. The control-oil group was given 2 ml corn oil and the control-water group was given water adlib. The treatments were done for 28 consecutive days and blood samples were taken by cardiac puncture. The following haematological parameters were analysed: RBC, WBC, Hb, PCV, MCV, MCH, MCHC and THR. Bone marrow smears were prepared on 14th and 28th days for various blood stem cells evaluation and spleen tissues for histopathology. There was a significant decrease (p ˂ 0.01) in RBC counts, PCV, MCV and MCH values, whereas the WBC, THR counts and MCHC values increased significantly (p ˂ 0.01) in dichlorvos treated rats as compared to the controls and dichlorvos + vitamins co-treated groups. There were no significant differences in blood parameter counts between controls and dichlorvos + vitamins co-treated groups. In the bone marrow smear of the dichlorvos treated group, there was increased number of megakaryocytes and mature neutrophils. In conclusion, findings from the current study revealed that, vitamins C and E supplements were capable of mitigating the haematotoxic effects induced by dichlorvos insecticide in Wistar rats.

Hematotoxicity induced by simultaneous exposure to noise and toluene in New Zealand white rabbits: Synergistic and antagonistic effects.

Exposure to numerous pollutants is prevalent in workplaces. Examination of combined exposure to different harmful physical factors and chemicals has offered new insights into toxicology in recent years. This study aimed to investigate the hematological alterations caused by exposure to noise and toluene. Twenty-four New Zealand white rabbits were exposed to 1000 ± 50ppm toluene and/or 100 ± 5dB noise for 14 consecutive days. Exposure to noise and toluene changed a number of parameters of white blood cells (WBC), red blood cells (RBC), and platelets on different days after the exposure. Simultaneous exposure to noise and toluene increased WBC, and exposure to noise and toluene alone decreased RBC. Exposure to noise and toluene alone increased basophile, monocyte, and neutrophil counts. The coefficient of variation of red blood cell distribution width (RDW-CV) and the standard deviation of red blood cell distribution width (RDW-SD) significantly increased after co-exposure to noise and toluene. Platelet levels increased in the noise-exposed and the co-exposed groups and decreased in the toluene-exposed group. Furthermore, co-exposure to noise and toluene induced dissimilar synergistic and antagonistic effects on the hematological indices. According to the results of this study, simultaneous exposure to toluene and noise can aggravate some hematotoxic effects compared to exposure to noise or toluene alone. The results also demonstrated the vital role of the modulatory mechanisms of the body in controlling the detrimental effects of stressors.

Features of anemia syndrome in women with endometrial hyperplasia working under the influence of organic solvents and depending on obesity

Introduction. Organic solvents have a hematotoxic effect, which leads to the development of anemia. Endometrial hyperplasia may also be the cause of a decrease in blood hemoglobin levels. The phenotype of anemia in combination of these diseases is still insufficiently studied. Exposure to organic solvents is associated with a carcinogenic risk, while their role in the development of precancerous conditions is little known.
 The study aims to research the features of anemia in patients with endometrial hyperplasia under the influence of organic solvents and depending on the obesity factor.
 Materials and methods. The design of the study is a single–center, single-stage observational. The researchers formed 2 groups of women with endometrial hyperplasia confirmed by histological examination, who worked under conditions of exposure to organic solvents (n=140, the main group, 70 of them obese according to WHO criteria) or who had no health risks (n=140, the comparison group, 68 of them obese). The patients of the main group are painters at a machine-building enterprise. Organic solvents concentrations at the workplace air were 1.2–5.0 times above occupational exposure limits, length of service was 21.5 (18; 28) years.
 Results. Scientists have registered anemia in 72.9% of obese workers, 54.2% of non-obese workers, 33.8% and 25.0% of patients in the comparison group with obesity and normal body weight, respectively, χ2=8.2, p=0.008. In contact with organic solvents, 60.7% of patients had anemia normal- or macrocytic, normal- or hyperchromic, hyporegenerative. In the subgroup of obesity and atypical endometrial hyperplasia, we have watched the minimum values of hemoglobin — 95 (90; 105) g/l and reticulocytes — 1 (0.5; 2), the maximum values of the average erythrocyte volume — 98 (92; 107) fl and the average hemoglobin content in the erythrocyte — 35(34; 38) pg. The researchers have determined the association of this variant of anemia with atypical endometrial hyperplasia by logistic regression, OR 2.51, 95% CI 1.08–5.85, p=0.033. In comparison group, all patients had iron-deficiency anemia.
 Limitations. The limitations of the study are related to the recruitment of patients in one center.
 Conclusion. Anemia in women with endometrial hyperplasia in conditions of organic solvents exposure is normo- or hyperchormic, normo- or macrocytic, hyporegenerative, most prominent in patients with obesity, and associated with atypical histological type of the disease.
 Ethics. The authors have carried out the study in compliance with the Ethical principles of conducting scientific medical research with human participation, set out in the Helsinki Declaration of the World Medical Association and in accordance with the Ethical norms and rules provided for by the Bulletin of the Higher Attestation Commission of the Ministry of Education of Russia No. 3 of 2002 "On the procedure for conducting biomedical research in humans". The study was approved by the Ethics Committee of the Federal State Budgetary Educational Institution of the Russian Ministry of Health.

Efek Hirupan Benzene (C<sub>6</sub>H<sub>6</sub>) Pada Sel Darah Merah Dan Sel Darah Putih Tikus Putih Jantan (<i>Rattus norvegicus</i>) Strain Wistar

In industry, "benzene" is frequently employed as a basic or compound substance. Exposure to "benzene" has hematotoxic effects on blood cell values, such as pancytopenia. In cases of cytopenia that cannot be explained, a blood smear evaluation is usually employed as a confirmation test and extra diagnostic help. The purpose of this study was to see how benzene inhalation affected blood smear examination in white male rats (Rattus novergicus) of the Wistar strain. True experimental design with simply a post-test control group. A total of 20 rats were separated into four groups. The non-benzene inhalation exposure group (K-) served as the negative control. The treatment groups ("P1, P2, P3") were given benzene inhalation at concentrations of 1, 10, and 100 parts per million, respectively. The exposure lasted 28 days, 8 hours per day, 5 days per week. The results were achieved by counting rat blood cells and examining their morphology under a microscope, after which an average number was calculated. Research and Discussion According to the ANOVA and Kruskal-Wallis test, the number of neutrophils and monocytes increased dramatically, whereas lymphocytes declined. Each group had a varied number of eosinophils, although the difference was not statistically significant. In the group exposed to 100 ppm benzene, the "Bonferoni and Mann-Whitney" post hoc test revealed a significant rise in the number of neutrophil segments and a decrease in the number of lymphocytes "(p0.05)". In the group exposed to 10 ppm benzene, there was a substantial rise in monocytes (p 0,05). The morphology of erythrocytes, leukocytes, and platelets yielded no aberrant results. Benzene inhalation exposure significantly affects the number of neutrophils segments, lymphocytes and monocytes, but has no effect on the number of other types of leukocytes. No abnormal morphology was found in erythrocyte, leukocyte, and platelets

ESTIMATION OF TOTAL LEUCOCYTE COUNT AND ERYTHROCYTE SEDIMENTATION RATE IN Channa punctatus (BLOCH.) UNDER TOXIC STRESS OF POTTERY CHEMICALS

The pottery and ceramic industry release toxic heavy metals during preparation and other steps which in turn go to environment and finally to aquatic ecosystem through leaching and runoff water. In the view of above facts it is mandatory to explore this non target effect of ceramic industry for aquatic ecosystem. A dye is a coloured material that chemically attaches to the substrate it is applied on. Dyes are distinguished from pigments by the fact that they do not chemically attach to the substrate they colour. In most cases, the dye is administered in an aqueous solution. Keeping these points in view, the present study is undertaken to assess impact of pottery industry chemical tin oxide on total leucocyte count and erythrocyte sedimentation rate of Channa punctatus (Bloch.). The TLC and ESR have been found to be increased after treatment due to hematotoxic effect of pottery chemicals and adverse effect on hemopoietic system of fish. Keywords: Channa punctatus (Bloch.), Pottery chemicals, Pottery industry, TLC, ESR

Fabrication, characterization, antimicrobial, toxicity and potential drug-delivery studies of PEGylated Sesamum indicum oil based nanoemulsion system

BackgroundThe actively mutating properties of disease-causing pathogens and GI intolerance associated with certain antibiotics among other challenges necessitated the adoption of colloidal system for drug delivery. Nanoemulsions (Ciprofloxacin (Cp) -loaded and non-drug loaded) were prepared by spontaneous emulsification method, characterized using Cryo-TEM, FTIR and Zetasizer. Antimicrobial activities were carried out using agar well diffusion method on Klebsiella pneumoniae and Bacillus subtilis. The in-vitro and dermal toxicological assessment were carried out using adult Wistar rats.ResultsThe Cryo-TEM micrographs showed spherical morphology while zetasizer results showed polydispersity index (PDI), mean droplet size and zeta potential (ZP) of 0.553, 124.3 ± 0.29 nm and − 15.3 mV respectively for non-drug loaded sesame oil-based emulsion (SOAB). While 0.295, 244.8 ± 0.33 nm and − 5.54 mV were recorded for Cp-loaded sesame oil-based emulsion (SOAB + Cp). The effective voltage charge of the emulsions was 147.4 V. FTIR results of Cp recorded O–H adsorption value of 3429 cm−1, while SOAB and SOAB + Cp showed superimposition at 3427.76 cm−1 showing no drug-excipient interactions. No skin irritation was observed after 14 days of skin corrosion assessment. No significant difference (p > 0.05) in body weight gain of both test and control animals, the treatment did not cause any observable alterations in blood-chemistry parameters and hematological indices. Photomicrographs of liver and heart shows an uncompromised histological architecture.ConclusionThe finding of the study shows a skin friendly, nanosized, spherical negatively charged emulsion with no cardiotoxic, hematotoxic and hepatotoxic effects on Wistar rats, and as such appears promising as a safe vehicle for drug delivery.Graphical

Quantum dots are time bomb: Multiscale toxicological study

The use of quantum dots has spread widely into many applications. Works on the study of quantum dots on living organisms have had conflicting results on toxicity. There are no full-scale long-term toxicological studies with multiple administration of quantum dots. Understanding the toxicity of quantum dots is still limited. Here we present data on the effects of quantum dots on animals. In this work for the first time, it is shown that at a single administration of quantum dots in the body they have moderate species-specific toxicity, but repeated administration of quantum dots for 14 days even in the amount of 0.5 mg/kg leads to a delayed not completely irreversible hematotoxic effect, delayed irreversible disorders of barrier function of the liver, irreversible nephrotoxic effect, and to pathological changes in the thymus, kidneys and spleen. Administration of quantum dots in the amount of 2.5 mg/kg for 14 days leads to irreversible changes in the lungs, liver, spleen, kidneys and thyroid gland. This phenomenon is based on immunological reactions. On the one hand, these data confirm that quantum dots at a single administration can show relatively low toxicity. On the other hand, they cause to a delayed irreversible organ and tissue damage when repeatedly administered to the body even in small quantities. This study demonstrates that quantum dots are not as low in toxicity as previously thought to be and pose a serious risk when entering living organisms. Detecting and treating poisoning using standard methods of diagnosis and treatment of heavy metal poisoning may not be effective. This study demonstrates that toxic effects of quantum dots on a living body are quite complex and cannot be generalized based on previously reported assumptions.

Nanocurcumin preserves kidney function and haematology parameters in DMBA-induced ovarian cancer treated with cisplatin via its antioxidative and anti-inflammatory effect in rats

Context Cisplatin, as a first-line treatment for ovarian cancer, is associated with debilitating adverse effects, including nephrotoxic and haematotoxic effects. Objective This study determines whether nanocurcumin, combined with cisplatin, would give additional benefit to kidney function and haematological parameters in rats with ovarian cancer. Materials and methods Twenty-five Wistar rats were divided into five untreated rats and 20-dimethylbenz(a)anthracene (DMBA)-induced ovarian cancer rats. The 20 ovarian cancer rats were divided into four treatment groups: vehicle, cisplatin, cisplatin-curcumin, and cisplatin-nanocurcumin. Cisplatin was given at the dose of 4 mg/kg BW once weekly, while curcumin or nanocurcumin was administered at 100 mg/kg BW daily for four weeks. At the end of treatment, we analysed kidney function, haematological parameters, and inflammatory and oxidative stress markers from plasma. Results Nanocurcumin alleviates the increase in kidney function markers and abnormalities in haematological indices in rats treated with cisplatin. Compared to cisplatin-treated rats, plasma urea levels decreased from 66.4 to 47.7 mg/dL, creatinine levels lowered from 0.87 to 0.82 mg/dL, and neutrophil gelatinase-associated lipocalin (NGAL) levels declined from 8.51 to 3.59 mIU/mg protein. Furthermore, the therapy increased glutathione activities (from 2.02 to 3.23 U/µL), reduced lipid peroxidation (from 0.54 to 0.45 nmol/mL), and decreased plasma TNF-α (from 270.6 to 217.8 pg/mL). Conclusions Cisplatin with nanocurcumin in an ovarian cancer rat model may provide additional benefits as a preventive agent against renal impairment and cisplatin-induced haematological toxicity. However, further research is required to prove that using nanocurcumin for a more extended time would not affect its anticancer properties.

Http://ukrbiochemjournal.org/2022/12/changes-in-the-activity-of-phosphatases-calcium-and-phosphorus-in-rats-with-the-different-courses-of-gingivitis-under-correction-by-anti-inflammatory-gel.html

Nitrate pollution of groundwater has been increasing in recent years. The aim of this work was to study the morphological features of the bone marrow of rats at the consumption of drinking water with varying nitrate content. The experiment was performed on 2 groups of white female rats of different ages (mature and immature) with 30 individuals each. Both groups were divided into 5 subgroups that differed in the quality of drinking water consumed by rats on their own. In the 30 days study, nitrate was given to rats in drinking water in doses of 50, 150, 250, 500 mg of sodium nitrate per liter. Animals of the control group drank water from the city water supply. The effect of nitrates on the bone marrow of rats was evaluated by morphological analysis. It was found that the consumption of drinking water with nitrates affected erythropoiesis and leukopoiesis, as evidenced by the growth of blasts, lymphocytes, pronormocytes and normocytes, megakaryocytes and eosinophils, displacement of erythrocyte sprout cells. An increase in the neutrophil maturation index indicates delayed neutrophil maturation, increased yield of mature cells from the bone marrow and depletion of the granulocyte lineage. The more pronounced changes were observed in the qualitative and quantitative composition of the components of the erythrocyte sprout. These disorders were dose-dependent with increasing hematotoxic effect of nitrates at doses of 250 and 500 mg/l in the group of immature animals and resulted in changes in the bone marrow, which may further cause the development of pathological processes in an organism. Keywords: bone marrow of rats, drinking water, nitrates, Van Gieson’s stain

Hematotoxic Effect of Respiratory Exposure to PHMG-p and Its Integrated Genetic Analysis.

Polyhexamethylene guanidine phosphate (PHMG-p), the main ingredient of humidifier disinfectants, circulates systemically through the lungs; however, its toxicological assessment has been primarily limited to pulmonary disease. Herein, we investigated the possible abnormalities in hematopoietic function 20 weeks after intratracheal instillation of PHMG-p in a rat model. Notable abnormalities were found out in the peripheral blood cell count and bone marrow (BM) biopsy, while RNA sequencing of BM tissue revealed markedly altered gene expression. Furthermore, signaling involved in hematopoietic dysfunction was predicted by analyzing candidate genes through Ingenuity Pathway Analysis (IPA) program. Respiratory PHMG-p exposure significantly decreased monocyte and platelet (PLT) counts and total protein, while significantly increasing hemoglobin and hematocrit levels in peripheral blood. Histopathological analysis of the BM revealed a reduced number of megakaryocytes, with no significant differences in spleen and liver weight to body weight. Moreover, PHMG-p exposure significantly activated estrogen receptor signaling and RHOA signaling, and inhibited RHOGDI signaling. In IPA analysis, candidate genes were found to be strongly related to 'hematological system development and function' and 'hematological disease.' Accordingly, our results suggest that PHMG-p could affect hematopoiesis, which participates in monocyte differentiation and PLT production, and may induce hematologic diseases via the respiratory tract.

Effects of sub-acute exposure to Sudan IV-adulterated palm oil on hematology-related parameters in male albino rats

ABSTRACT Palm oil (PO), the most consumed edible oil, is persistently adulterated with Sudan IV dye (S4D). We investigated the potential hematological derangements occasioned by ingesting S4D-adulterated PO. Thirty male albino rats were grouped into five (n = 6); Control, PO (10%), PO + S4D (100 mg), PO + S4D (250 mg), and S4D (250 mg). Rats received unadulterated or S4D-adulterated PO through diet for 21 days. Exposure to S4D (alone and via adulterated PO) provoked significant (p < 0.05) reductions in the packed cell volume, hemoglobin, red and white blood cell counts, neutrophils, lymphocytes, and eosinophils, while monocyte population was significantly (p < 0.05) elevated. The erythropoietin gene expression was downregulated, while monocyte chemoattractant protein-1 was upregulated in the kidneys of S4D-exposed groups compared to control and PO-alone groups. Notably, these hematological parameters were not significantly different (p > 0.05) in the unadulterated PO-exposed rats compared to the control. These results reveal the potential hematotoxic and immunotoxic effects of adulterating PO with S4D.