Hematotoxic Effects Research Articles

Chemical profile and in vivo toxicity evaluation of unripe Citrus aurantifolia essential oil.

Citrus aurantifolia (Christm.) Swingle (syn. C. MEDICA var. ACIDA Brandis) (family: Rutaceae) essential oil is one of the cheapest oils found in local markets. Although, it is generally accepted as non-toxic to vital organs and cells, majority of people are cynical about it usage. Herein, the present study reports the chemical composition and in vivo oral toxicity study of unripe C. aurantifolia essential oil found in Ghana. The toxicity of C. aurantifolia essential oil extract was investigated via oral administration using two methods: The acute toxicity single dose study (SDS) and the repeated dose method. The oil exhibited no acute toxicity but in the sub-chronic studies, the effects was dose and time-dependent. Chemical profile investigation of the oil showed 9 constituent of phytochemicals (Germacrene isomers (61.2%), Pineen (14%), Linalool dimmer (2.9%), Bornane (11%), Citral (2.9%), Anethole (1.5%), Anisole (1.1%), Safrole (0.3%) and Demitol (0.6%)). Histopathological studies revealed conditions such as necrosis, edema and inflammatory reaction in the liver, spleen and kidneys. Marginal upsurge of biochemical parameters above normal and elevated levels of lymphocytes (35.20-46.40 g/dL) demonstrated mild toxicity among the 100 mg/kg and 500 mg/kg dose groups at the sub-chronic stage. Low levels of hemoglobin (13.60 to 12.70 g/dL), MCV (34.20-24.0 fL), MCH (40.20-36.40 g/dL) along with high levels of liver enzymes confirmed the mild toxicity of the oil at sub-chronic stage. These results demonstrate that, despite consideration of lime essential oil as safe, it can have mild hematotoxic, nephrotoxic and hepatotoxic effects.

Human exposure to mercury and its hematological effects: a systematic review.

Mercury is a metal found in the environment from natural and anthropogenic sources. It is highly toxic to ecosystems and living beings. Most human exposures come from ingestion of contaminated seafood, outgassing from dental amalgam or occupational exposure (e.g. gold mining), among other cases. Large populations are exposed to mercury, making it a very important issue from the public health perspective. Adverse health effects are commonly seen in the nervous system, but every organ is a potential target, such as the bone marrow. The main goal of this study was to assess the available evidence on human exposure to mercury and its hematological effects. A search strategy was constructed, including key terms (MeSH, text word and equivalents) for querying 2 repositories of master dissertation and PhD thesis (Fiocruz/ARCA and University of São Paulo) and 4 different electronic databases: BVS/LILACS, MEDLINE/PubMed, Scopus and TOXLINE/NIH, for articles published from 1950 to February 2018. There was no language restriction and a tool (EPHPP) was used to assess the quality of included studies. According to pre-established criteria, 80 studies were retrieved, all of them observational (48 case reports, 24 cross-sectional, 6 case series and 2 cohorts), comprising 9,284 people. Despite the fact that most exposed ones (6,012) had normal blood cell count and mercury hematological effects did not seem very usual (1,914 cases: 14 severe and 29 deaths), three studies reported association (β) for anemia, lymphopenia, neutrophilia and basophilia. We concluded that the gathered information pointed to mercury hematotoxic effects, some of them may be serious and even fatal.

Estimation of lead in blood donors of Dakshina Kannada population in relation to smoking

IntroductionLead is a toxic heavy metal with hematotoxic, neurotoxic, and nephrotoxic effects even at low concentration. Presence of heavy metals like lead in the blood and blood products while donating blood can cause adverse effects to the recipients.MethodologyIn this study, we have selected 130 volunteers from the donors list obtained from Yenepoya hospital and also from in and around Mangalore. Questionnaires was given to the volunteers to get information on smoking, passive smoking at home or at the work place, duration of smoking, occupation and health status. Whole blood samples were subjected to Atomic Absorption Spectrometer (AAS) and results were obtained.ResultsLead content in smokers were found to be 2–3 times higher compared to non-smokers but were in below toxic range (~5 ppm).ConclusionThere are no present protocol to screen for heavy metals like lead in the blood banks. Our findings implicate the need to screen for heavy metals while transfusing blood to elderly people, neonates and infants and avoid transfusion of blood and blood products if the lead levels are in toxic range.

Preclinical Evaluation for the Gene Therapy of Patients with Leukocyte Adhesion Deficiency Type I

Leukocyte Adhesion Deficiency Type I (LAD-I) is a severe primary immunodeficiency characterized by recurrent and life-threatening bacterial infections. It is caused by mutations in the ITGB2 gene, encoding the integrin β2 common subunit (CD18). These mutations lead to defective or absent expression of β2 integrins on leukocyte surfaces, rendering leukocytes unable to extravasate to infection sites. Severe LAD-I is characterized by less than 2% of normal CD18 neutrophil expression and is fatal during the initial 2 years of life in 60-75% of patients in the absence of allogeneic hematopoietic transplant. As it is the case with other monogenic immunodeficiencies, LAD-I is a disorder that could be corrected by ex vivo gene therapy. To this aim we have developed a lentiviral vector (LV) that has recently obtained the Orphan Drug designation (EU/3/16/1753 and DRU-2016-5430). In this LV the expression of hCD18 is driven by a chimeric promoter with a higher activity in myeloid cells. Comprehensive safety and efficacy preclinical LV-mediated gene therapy studies have been conducted in LAD-I mouse models harboring either hypomorphic or knock-out mutations in the ITGB2 gene. Our studies demonstrate stable engraftment of gene corrected LAD-I mouse hematopoietic stem cells in LAD-I recipients and indicate a phenotypic correction of peripheral blood neutrophils. A complete preclinical safety evaluation of the vector was also carried out demonstrating the absence of hematotoxic and genotoxic effects in treated animals. Further studies have been conducted with GMP-produced LVs in human CD34+ cells aimed at optimization of cell transduction. The use of transduction enhancers (TEs) significantly improved the efficacy of genetic correction of human CD34+ cells transduced with LVs at low MOIs. Additionally, transplants into immunodeficient mice showed no changes in the repopulating ability of CD34+ cells when these cells were transduced in the presence of TEs. As occurred in in vitro cultures, significant increases in the transduction of repopulating cells were also associated with the use of TEs, indicating that optimized TE combinations will enable practical and cost-effective transduction of human HSCs in gene therapy protocols. Taken together, these results demonstrate the efficacy and safety of a gene therapy approach directed towards the therapy of LAD-I patients. DisclosuresAlmarza:Rocket Pharmaceuticals: Equity Ownership, Patents & Royalties, Research Funding. Schwartz:Rocket Pharmaceuticals: Employment, Equity Ownership. Bueren:Rocket Pharmaceuticals: Consultancy, Equity Ownership, Patents & Royalties, Research Funding.

ЗМІНИ ГЕМОПОЕЗУ В КІСТКОВОМУ МОЗКУ ТА СЕЛЕЗІНЦІ ЩУРІВ WISTARHAN ЯК МЕХАНІЗМ ГЕМАТОТОКСИЧНОЇ ДІЇ ТЕБУКОНАЗОЛУ

Вступ. Однією з найбільш застосовуваних діючих речовин фунгіцидів триазольної групи є тебуконазол. Проведені раніше дослідження периферичної крові показали його гематотоксичну дію. 
 Мета дослідження – вивчити процеси кровотворення в кістковому мозку та селезінці щурів-самців WistarHan при гострій інтоксикації тебуконазолом технічним, 97 %.
 Методи дослідження. Статевозрілим щурам-самцям WistarHan, поділеним на контрольну (0 мг/кг) та 2 експериментальні групи, одноразово внутрішньошлунково через зонд було введено токсичну дозу тебуконазолу – 1700 мг/кг маси тіла (1/2 від ЛД50). Периферичну кров досліджували на 0, 1, 3, 7 та 14 постекспозиційні доби. Вивчали гематологічні показники: кількісний вміст еритроцитів та ретикулоцитів, концентрацію гемоглобіну, рівень гематокриту, еритроцитарні індекси, кількість лейкоцитів і тромбоцитів. Гемограму з морфологічною оцінкою клітин крові аналізували в мазках периферичної крові. Гемопоез у кістковому мозку (мієлограма) та селезінці (спленограма) досліджували на 7 і 14 постекспозиційні доби.
 Результати й обговорення. Встановлено анемізуючу дію, ретикулоцитопенію та появу макрофагів у периферичній крові. У кістковому мозку відмічено пригнічення еритропоезу з порушенням процесів гемоглобіноутворення в нормоцитах, у селезінці розвинулось екстрамедулярне кровотворення. Встановлено супресивну дію на клітини еозинофільного та базофільного рядів. Спостерігали компенсаторну активізацію нейтрофілопоезу, лімфоцитопоезу та моноцитопоезу в кістковому мозку.
 Висновок. Встановлено декілька механізмів гематотоксичної дії тебуконазолу технічного, 97 %: порушення гемоглобіноутворення, депресію еритропоезу з патологічною регенерацією, розвиток екстрамедулярного кровотворення в селезінці та вплив на деякі ланки імунітету.

Hematologic Perturbations among Pesticide Applicators Recently Exposed to Permethrin in the Agricultural Health Study

In the Agricultural Health Study (AHS), a large prospective cohort of pesticide applicators, exposure to the pyrethroid insecticide permethrin is associated with an increased risk of multiple myeloma (MM), a hematologic malignancy with an unfavorable prognosis. To gain insight into the biological mechanisms underlying this association, we assessed potential hematotoxic effects of permethrin, in a longitudinal study of 35 permethrin-exposed male pesticide applicators in the AHS. Serial blood samples were collected from each participant in the off-season, the day after permethrin use, and approximately 3 weeks after use. At each time point, we performed a complete blood count with white blood cell differential and measured lymphocyte subsets. We used linear mixed models to assess the relationship between permethrin exposure and cell counts, controlling for season, age, BMI, recent cold/infection (≤7 days), and use of other pesticides (≤30 days). We observed a statistically significant increase in the geometric mean of immature granulocytes (31%, 95% CI=6%, 63%) on the day after permethrin use relative to off-season levels, but not 3 weeks after use. Statistically significant (P<0.05) alterations in several red blood cell parameters were also observed on the day after permethrin use, including decreased red blood cell count, hemoglobin, and hematocrit and increased mean corpuscular volume and red blood cell distribution width-SD. Red blood cell count, hemoglobin, and hematocrit remained significantly decreased 3 weeks after permethrin use. Increased immature granulocytes are indicative of an inflammatory response and enhanced bone marrow activity, and sustained decreases in red blood cell parameters may be a result of increased oxidative stress. Our results suggest inflammatory and hematologic effects of permethrin exposure, and identify targeted cell populations for future mechanistic studies to elucidate the relationship between permethrin use and MM risk.

Hemolytic anemia incident in leprosy patients receiving multi-drug therapy at Haji Adam Malik Central Hospital, Medan-Indonesia.

Introduction: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae ,which is an obligate intracellular bacteria. The therapy of leprosy involves a combination of drugs called multi-drug therapy and one of the drugs included in this therapy is dapsone. Dapsone has a hematotoxic effect because of its toxic metabolite called hydroxilamine. The most common side effect of this drug is hemolytic anemia. Hemolytic anemia occurs when the production of erythrocytes is not balanced with their destruction, causing the lifespan of erythrocyte to become shorter and the bone marrow fails to compensate for this. Methods: This research is a pre experimental study with a pre-post design, involving 15 leprosy patients that were diagnosed by clinical and laboratory examination. We conducted measurements of hemoglobin, MCV, MCHC, and reticulocyte count before and after the MDT therapy for 3 months. Results: In this study, the incidence of hemolytic anemia after 3 months receiving MDT was 66.7%. There was decreased hemoglobin level (mean 11.320 g/dl), increased reticulocyte count (mean 2.341%), normal level of MCV (mean 88.807 fL), and decreased level of MCHC (mean 31.920 g%). There were significant differences in hemoglobin level, MCHC level, and reticulocyte count before and after 3 moths of MDT.Conclusion: There was a significant difference in the number of hemolytic anemia before and after MDT with a p-value < 0.05.

Comparative haemato-immunotoxic impacts of long-term exposure to tartrazine and chlorophyll in rats

The haemato-immunotoxic effects of the food colourants tartrazine and chlorophyll were evaluated. Thirty adult Sprague Dawley rats were distributed into three groups and orally administered water, tartrazine (1.35 mg/kg), or chlorophyll (1.35 mg/kg) daily for 90 days. Erythrogram and leukogram profiles were evaluated. The lysozyme, nitric oxide, phagocytic activity, and immunoglobulin levels were measured. Histological and immunohistochemical evaluations of splenic tissues were conducted. Changes in the interleukin (IL) 1β, 6, and 10 mRNA expression levels were assessed. In the tartrazine-treated rats, a significant anaemic condition and marked leukocytosis were observed. Both the innate and humoural parameters were significantly depressed. Different pathological lesions were observed, including red pulp haemorrhages, vacuolation of some splenic cells, focal hyperplasia of the white pulp, and capsular and parenchymal fibrosis. A marked increase in vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (e-NOS) immunolabelling was evident. Marked upregulation of IL-1β, IL-6, and IL-10 was recorded. In contrast, the chlorophyll-treated rats showed minimal haemato-immune responses. These results indicate that tartrazine exerts haematotoxic and immunotoxic effects following long-term exposure, whereas chlorophyll is a less hazardous food colourant.

Effects of the food additives sodium acid pyrophosphate, sodium acetate, and citric acid on hemato-immunological pathological biomarkers in rats: Relation to PPAR-α, PPAR-γ and tnfα signaling pathway

The food additives sodium acid pyrophosphate (SAPP), sodium acetate (SA), and citric acid (CA) were evaluated for their hemato-immunotoxic effects. Forty adult Sprague-Dawley rats were distributed into four groups and were orally administered water, SAPP (12.6 mg/kg), CA (180 mg/kg), or SA (13.5 mg /kg) daily for 90 days. Erythrogram and leukogram profiles were evaluated. The levels of lysozyme, nitric oxide, immunoglobulin, and phagocytic activity were measured. Histologic and immunohistochemical evaluations of splenic tissues were performed. Changes in the mRNA expression levels of peroxisome proliferator-activated receptor α and γ (PPAR-α and PPAR-γ), and tumor necrosis factor α (TNF-α) genes were assessed. A significant leukopenic condition was observed with SAPP, while CA induced marked leukocytosis, and SA showed a lymphocytosis condition. Both the innate and humoral parameters were significantly depressed. Various pathological lesions were observed, including diffuse hyperplasia of the red pulp, depletion of the white pulp, and capsular and parenchymal fibrosis. A marked decrease in CD3 T-lymphocyte and CD20 B-lymphocyte immunolabeling in rats treated with SAPP and SA was evident. Marked downregulation of PPAR-α and PPAR-γ together with upregulation of TNF-α was recorded. These results indicate that high doses of SAPP, SA and CA exert hematotoxic and immunotoxic effects with long-term exposure.

Computational Assessment of Pharmacokinetics and Biological Effects of Some Anabolic and Androgen Steroids.

The aim of this study is to use computational approaches to predict the ADME-Tox profiles, pharmacokinetics, molecular targets, biological activity spectra and side/toxic effects of 31 anabolic and androgen steroids in humans. The following computational tools are used: (i) FAFDrugs4, SwissADME and admetSARfor obtaining the ADME-Tox profiles and for predicting pharmacokinetics;(ii) SwissTargetPredictionand PASS online for predicting the molecular targets and biological activities; (iii) PASS online, Toxtree, admetSAR and Endocrine Disruptomefor envisaging the specific toxicities; (iv)SwissDock to assess the interactions of investigated steroids with cytochromes involved in drugs metabolism. Investigated steroids usually reveal a high gastrointestinal absorption and a good oral bioavailability, may inhibit someof the human cytochromes involved in the metabolism of xenobiotics (CYP2C9 being the most affected) and reflect a good capacity for skin penetration. There are predicted numerous side effects of investigated steroids in humans: genotoxic carcinogenicity, hepatotoxicity, cardiovascular, hematotoxic and genitourinary effects, dermal irritations, endocrine disruption and reproductive dysfunction. These results are important to be known as an occupational exposure to anabolic and androgenic steroids at workplaces may occur and because there also is a deliberate human exposure to steroids for their performance enhancement and anti-aging properties.

Assessment of Hematotoxicity and Genotoxicity among paint Workers in Assiut Governorate: a case control study

BackgroundOccupational exposures to hazardous chemicals in paints cause serious health hazards in painters. The present study was designed to evaluate the possibility of hematotoxic and genotoxic effects of paint chemicals among painters in Assiut Governorate, Egypt. In addition the role of oxidative stress and apoptosis in mechanism of such toxic effects were studied.MethodsA case control study was performed on 50 male painters and 50 non-exposed healthy subjects, who were included as a control group after informed consent. Venous blood samples were obtained and analyzed for determination of total and differential blood count as hematotoxic markers as well as serum malondialdehyde (MDA) as an oxidant stress markers and total antioxidant enzymes. In addition, human B-cell lymphoma-2 (Bcl-2), caspase-3 and 8-hydroxyguanosine (8-OHdG) were assayed as markers of apoptosis and genotoxicity.ResultsThere was a statistically significant difference between paint workers and controls as regard total and differential blood count, serum MDA and total anti-oxidant levels. Also, statistical significant differences in caspase-3, Bcl-2 levels and 8-OHdG were observed.ConclusionsChronic occupational exposure to paints increased the risk of hematotoxicity and genotoxicity in painters. Oxidative stress and apoptosis play a major role in such mechanism. Periodic medical examination and application of protective devices is necessary.

Проблема оцінки гематотоксичності пестицидів

Introduction. The article presents the results of studies of hematoxicity of pesticides, which at the present stage acquire special significance in connection with the widespread use of pesticides. The obtained data testify to the need for laboratory monitoring of the effectiveness and safety of the use and accumulation of pesticides in the environment and in humans and animals, therefore they justify the urgency of preventing side effects of pesticide preparations. The author came to the conclusion that when carrying out hematological studies with a diagnostic purpose, it is necessary to take into account the changes that arise in the blood system under the influence of potential toxicants, including drugs. In order to prevent hematotoxic effects, pharmacotherapy should strictly adhere to metered regimens and regimens.The need to study the state of the blood system is dictated, first of all, by its importance for maintaining the constancy of the internal environment of the organism and the risk of the emergence of various pathological conditions when the functioning of the blood system is disturbed. It is especially important to note the relevance of differential diagnosis of blood damage and diseases that occur with lymphoproliferative and autoimmune syndromes. Taking this into account, it is necessary to note the importance of differential diagnosis of leukemoid reactions arising from exposure to potential toxicants.The current state of control of the side effects of pesticides does not provide an opportunity to objectively assess the significance of the problem of medicinal and pesticidaltoxicoses and the post-toxication complications caused by them, including the risk of hematotoxic effects. The potential risk of hematotoxic complications is the violation of the basic functions of the blood.The aim of the study – to note the importance of research and a deeper study of the processes that arise when the blood system is exposed to potentially dangerous chemicals (XP) and leads to the development of hematological dysfunctions.Conclusions. The effect of substances of various groups of pesticides on the blood system was established, violations of hematological parameters of peripheral blood and their connection with morphological indices under conditions of exposure to potential toxicants were revealed, which is of fundamental importance in the diagnosis of hematotoxic effects.

СОРБЦИОННЫЕ СВОЙСТВ ЦЕОЛИТА ХОТЫНЕЦКОГО МЕСТОРОЖДЕНИЯ И ПЕРСПЕКТИВЫ ЕГО ПРИМЕНЕНИЯ КАК ЭНТЕРОСОРБЕНТА

This work is aimed at investigating the sorption properties of Zeolite in the Khotynetsky deposits. A syste-matic study was conducted to examine the sorption properties of the natural Zeolite mined in the Khotynetsky deposits towards a number of toxic subtances: heavy metals (Hg, Pb, As, Cd, Zn, Ni), antibiotics (tetracycline, doxycycline, levomycetin and penicillin) and polycyclic aromatic hydrocarbons (benzo(a)pyrene). Water and food are the main sources of heavy metals in the body. Benzo(a)pyrene is known to be a highly toxic carcinogen belonging to the class of polycyclic aromatic hydrocarbons. This substance exhibits mutagenic, embryotoxic and hematotoxic effects, thus contributing to the development of malignant tumors. For all the studied toxicants, we have determined the effect of medium acidity and sorption time on the substance extraction, the sorption capacity of Zeolite and respective sorption isotherms. A relationship between the destruction of the Zeolite structure and its sorption properties is presented, taking into account the acidity of the medium. The data obtained are of practical interest and can be used for the development of recommendations concerning the application of Zeolite from the Khotynetsky deposits as an enterosorbent. Such recommendations can facilitate the development of diet optimization models in terms of the amount and combination of pharmaceutical biologically active substances.

Aberrant promoter methylation in genes related to hematopoietic malignancy in workers exposed to a VOC mixture

Occupational exposure to volatile organic compounds (VOCs) may cause hematopoietic malignancy, either by single exposure to benzene or possibly due to a concomitant exposure to several VOCs. Since oxidative stress, inflammation and DNA repair pathways are closely involved in cancer development, the effect of VOC exposure on expression of proteins involved in these pathways has been studied, but epigenetic changes have not been well described. Here, DNA methylation status following occupational exposure to a VOC mixture was assessed by bisulfite sequencing of the promoter regions of seven genes involved in the mentioned pathways. Peripheral blood samples and individual-level VOC exposure data were obtained from healthy leather shoe factory workers (LS, n=40) and gas station attendants (GS, n=36), as well as a reference group of university employees (C, n=66). Exposure levels for acetone, ethylbenzene, methyl ethyl ketone, n-hexane, toluene and xylene were higher in LS (p<0.001); benzene and methyl acetate levels were higher in GS (p<0.001). TOP2A, SOD1, and TNF-α promoter methylation status was increased in LS (p<0.05). In LS, we also found significant correlations between GSTP1 promoter methylation and both iNOS (r=0.37, p=0.008) and COX-2 (r=−0.38, p=0.007) methylation. In exposed groups, ethylbenzene exposure levels showed a significant correlation with TOP2A methylation (β=0.33). Our results show early, toxic effects at the epigenetic level caused by occupational exposure to high levels of a VOC mixture. These subcellular modifications may represent the initial mechanism of toxicity leading to hematopoietic malignancy, possibly due to a synergistic, hematotoxic effect of VOC mixtures.

The Hepatoprotective Effect of Gallic Acid on Mercuric Chloride-Induced Liver Damage in Rats

Background: Mercury has a variety of industrial applications and is well-known for its hematotoxic, hepatotoxic, neurotoxic, nephrotoxic, and genotoxic effects. Objectives: This study was carried out to assess the protective effects of gallic acid against mercuric chloride-induced oxidative stress in albino rats. Methods: A total of 35 male Wistar rats were divided into 5 groups (7 rats per group). Groups 1 and 2 were used as the negative and positive controls, respectively and received normal saline (2 mL/kg/day, po) and mercuric chloride (0.4 mg/kg/day, po) for 28 days. Group 3 only received gallic acid (200 mg/kg/day, po) for 28 days, whereas groups 4 and 5 received gallic acid (50 and 200 mg/kg/day, respectively) after 1 hour, followed by mercuric chloride (0.4 mg/kg/day, po) for 28 days. Results: The results demonstrated that treatment with gallic acid significantly diminished the mercuric chloride-induced increase in the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lipid peroxidation in liver tissues. In addition, gallic acid treatment increased the level of glutathione peroxidase, superoxide dismutase, and catalase activity and lowered the glutathione level in liver tissues, compared to the mercuric chloride group. The liver of rats, treated with mercuric chloride, showed degenerated cells (with mild cytoplasmic vacuolation and blebbing), binucleated cells, and significant sinusoidal dilation. Conclusions: It can be concluded that gallic acid restores the activities of antioxidant enzymes and tissue markers in mercuric chloride-treated rats, probably by scavenging free radicals and improving the antioxidant defense mechanisms. © 2017.

POLYSACCHARIDES OF TUSSILAGO FARFARA L. AS COMPONENTS OF CHEMOTHERAPY SCHEME

It was found that the addition of polysaccharides of Tussilago farfara L. to chemotherapy scheme “cisplatin + etoposide” lead to more pronounced inhibition of the Lewis lung carcinoma growth in mice due to the reduction of its mass in comparison with these parameters in animals treated according to the same scheme isolated. A use of polysaccharides of Tussilago farfara L. could reduce the hematotoxic effect of polychemotherapy with the “cisplatin + etoposide” scheme, which was expressed in a decrease of leukopenia and anemia.

Evaluation of the role of captopril on clozapine-induced cardiotoxicity and hematotoxicity in adult male albino rats

Clozapine (CLZ) is considered the most effective drug in treatment of resistant schizophrenia. However, its cardiotoxic effect has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with unique antioxidant properties. The aim of this study was to investigate the protective effect of captopril against CLZ-induced myocarditis, and since both drugs have hematotoxic effects, this study aimed to clarify the effect of their combined use on the bone marrow. The study was conducted for 4 weeks on 50 adult male albino rats divided into five groups: group I (negative control), group II (positive control), group III treated with captopril 5 mg/kg/day, group IV treated with CLZ 25 mg/kg/day, and group V treated with captopril (5 mg/kg) 1 hour before CLZ (25 mg/kg/day). CLZ group showed a significant increase in serum troponin I, marked histopathological changes, and immunohistochemical staining of DNA degradation product 8-hydroxy-2-deoxy guanosine (8-OHdG). It significantly increased malondialdehyde level and decreased glutathione peroxidase. Captopril coadministration decreased the histopathological hallmarks and biochemical marker of myocarditis and attenuated CLZ effects on the oxidative stress parameters and 8-OHdG, suggesting its protective action against CLZ-induced myocarditis. Complete blood count and bone marrow evaluation was normal indicating that captopril, in the protective dose given, didn’t increase the risk of CLZ-induced hematotoxicity

Protective role of quercetin against hematotoxic and immunotoxic effects of furan in rats.

Furan (Fu) is a liver carcinogen produced during heating process of food and concerns a public health problem. The current study was undertaken to evaluate the protective role of quercetin (Que) on Fu-induced hematological, immunological, and histopathological alterations in rats. Fifty male Sprague Dawley rats were divided into five equal groups. Group I (Cont) received distilled water, group II (CO) received corn oil, group III (Que) received Que at 50 mg/kg BW, group IV (Fu) received Fu at 16mg/kg BW, and group V received Que + Fu simultaneously; all groups gavaged daily for 30days. Our results revealed that Fu administration significantly elevated RBCs, Hb, PCV, WBCs, lymphocytes, and granulocytes and reduced phagocytic percent (Ph%) and index (PhI). Fu decreased the serum total protein, albumin, globulin, IgM, IgG, and IL4, with a significant increase in the TNFα and 8-OHdG. Moreover, it decreased the GSH content and GST activity and increased the MDA levels in the splenic tissue. Histopathologically, Fu led to a moderate depletion in the lymphoid cells and weak immunostaining of CD20 antigen of few lymphocytes appeared in the spleen. Meanwhile, Que co-administration ameliorated the altered hematological parameters and improved the Ph% and PhI. It modulated the serum biochemical parameters and immunoglobulins. Moreover, it decreased lipid peroxidation and enhanced antioxidant status in the spleen. The results indicated that Que possesses antioxidant protective activity against Fu-induced oxidative damage and stimulates the immune function.

Cadmium, iron and zinc interaction and hematological parameters in rat dams and their offspring

The effects of cadmium (Cd) were evaluated in offspring exposed from birth until weaning (neonatal day 0–21) and 4 weeks after exposure cessation focusing on iron (Fe) and zinc (Zn) levels in organs and hematological parameters. Wistar female rats were administered 50mg Cd/L in drinking water (Cd-exposed) for 4 weeks before mating and during 3 weeks of gestation plus 3 weeks of lactation. Controls were supplied drinking water. At birth, part of Cd-exposed dams’ litters was cross-fostered to control dams (CCd group) and their control litters were cross-fostered to Cd-exposed dams (CdC group). This procedure enabled to discern the effects of gestational, lactational and gestational plus lactational Cd exposure until weaning in F1 offspring. Elements were analyzed by atomic absorption spectrometry; hematological parameters manually; and histopathological changes by light microscopy. Gestational plus lactational exposure in Cd-exposed dams and their offspring increased Cd and decreased Fe levels, increased Zn in dams and decreased Zn and body weights in 11- and 21-day pups. In 21-day weanling pups, decreased red blood cell (RBC) count, hemoglobin and hematocrit values and increased reticulocytes in peripheral blood were also found with concomitant histopathological finding of extramedullary hematopoiesis in the liver. In cross-fostered pups with gestational exposure (CCd pups), Fe in the liver decreased on day 11 and Zn increased in the kidney on day 21 whereas in pups with lactational exposure (CdC pups) Zn in the brain decreased on day 11 and Fe decreased in the liver and brain on day 21. Regardless of exposure cessation at weaning, in offspring with gestational plus lactational exposure (Cd-exposed) body weights, kidney and brain Fe levels and RBC and hemoglobin remained decreased in blood until puberty. Furthermore Zn levels increased in the liver, kidney and brain. It was concluded that gestational plus lactational Cd exposure caused decreases in Fe and Zn levels and hematotoxic effects in F1 offspring more pronouncedly than exposure during either gestational or lactational period alone and the adverse effects of maternally mediated Cd exposure continued after exposure cessation into adulthood.

TOXICOLOGICAL STUDY ON THE HEALTH EFFECTS OF LONG TERM EXPOSURE TO BENZENE IN BENZENE FILLING WORKERS, QASSIM REGION, KSA

Background: Benzene is the smallest and most stable aromatic hydrocarbon, used as an excellent solvent in various industries. Occupational exposure to benzene has been associated with various adverse health effects in humans. Objective: This study was conducted to evaluate the dermatoxic, hematotoxic, hepatoxic and nephrotoxic effects related to long term exposure to benzene in benzene filling workers. Materials and methods: 72 male patients attended at the dermatological clinic, Buraydah central hospital, Qassim region, KSA, seeking medical treatment, over one year (Jumada I 1433 – Jumada I 1434), were included in this study after an informed written consent. They were divided into two groups (GI & GII): 47 patients who are benzene filling workers in fueling station (GI) and 25 patients who already work in stations as overseers (GII). Full dermatological examination was done for all participants. Blood benzene level was determined by GC mass spectrometry method. Complete blood count (CBC), liver function and kidney function tests were examined. Results: Allergic ((34.04%) and fungal (19.15%) diseases were the most common diagnosed problems in GI with high benzene level (227.83 ± 10.32 ng/l) in comparison to GII (163.04 ± 26.48 ng/l). WBCs count, neutrophil count, monocyte count, lymphocyte count, eosinophil count and basophil count were significantly higher in GI in comparison to GII, (p 0.05). The mean value of (ALT) (65.12 ± 14.3) and (AST) (63.25 ± 15.1) in GI was significantly increased (p=0.046 and p=0.035 respectively) than the corresponding values in GII (41.40 ± 13.11 and 40.23 ± 16.5 respectively). No significant differences were obtained in urea and creatinine levels between the two groups. Conclusion: This study suggests that long term benzene exposure causes dermatotoxic effects that enhance incidence of skin diseases. Blood disorder and liver involvement in these workers are possible and full attention should be given in medical surveillance of benzene workers.