Benzene Intoxication Research Articles

Myeloprotective and Hematinic Influence of Harungana madagascariensis in Benzene-initiated Onco-hematologic Process in Wistar Rats

Background: Harungana madagascariensis is a medicinal plant that is traditionally utilized for the treatment of anaemia. Benzene constitutes an occupational toxicant due to its adverse effect on hematology of exposed industrial workers leading to onco-hematology. Therefore, the efficacy of Harungana madagascariensis against benzene-induced pre-leukaemic condition was investigated in rat model.
 Methodology: Hematological disturbance leading to pre-leukemic conditions was induced in Wistar rats by intraperitoneal administration of 400mg/kg of benzene in propan-2-ol:water (1:1 v/v) every other day for 28 days. Following benzene intoxication, 200 mg/ kg HM was administered orally for 14 days. Hematological parameters and blood cell morphology were compared between baseline control and benzene-intoxicated rats with or without HM extract treatment.
 Results: BZ-induced hematologically disturbed rats exhibited anaemic symptoms marked by reduction in hemoglobin level, red blood cells, and packed cell volume with morphologic blast cell appearance, polychromasia, hypersegmented neutrophil, anisocytosis and poikilocytosis. Moreover, there was an altered redox status depicted by a significant reduction in plasma level of total sulfhydryl content with concomitant increase in advanced oxidation protein products (AOPPs) that were accompanied by increased frequency of micronucleated polychromatic erythrocytes and hypercellularity in the bone marrow of benzene intoxicated rats. However, treatment with Harungana madagascariensis restored blood hematology and alleviated the blood cell morphological alteration induced by benzene. It also improved plasma redox status, reduced the frequency of micronucleus and improve the architecture of bone marrow cellularity in treated intoxicated rats.
 Conclusion: Harungana madagascariensis protected against benzene-induced hematological alterations leading to pre-leukemic conditions in Wistar rats.

Hepatoprotective Effect of Eulophia gracilis on Benzene-Induced Liver Toxicity in Wistar Rats

Benzene (BZ) is an organic solvent that can induce pathological disorders such as haematological disburbance and liver damage. Eulophia gracilis (EG) plant is a medicinal orchid explored traditionally to treat myriads of ailments including anemia and liver disease. The present study investigated the protective effect of Eulophia gracilis extract against Benzene-induced hepatotoxicity in haematologically disturbed rats. Male Wistar rats (110-120 g) were randomized into four groups (n = 6 / group): I (control), II BZ-treated: 175 mg/kgbw benzene every alternate days for two weeks; III Co-treated with 175 mg/kgbw benzene and E. gracilis 200 mg/kgbw each day for two weeks and IV administered 200 mg/kg of E. gracilis for two weeks. BZ caused a significant reduction in PCV, Hb, RBC and altered white blood cell count. Similarly, activities of hepatic biomarker enzymes such as alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase were significantly increased in the BZ-treated group relative to control. Furthermore, BZ caused a significant decrease in the activities of hepatic arylesterase, superoxide dismutase, catalase and glutathione-S-transferase and levels of Ascorbic Acid (AA) and Glutathione (GSH). A significant increase in hepatic malondialdehyde content, altered liver ultrastructure and modulation of p53 and BCl-2 protein in the liver also accompanied benzene intoxication. However, coadministration of E. gracilis ameliorated the BZ-induced changes in haematological parameter and liver biomarkers and improved hepatic antioxidant biomarkers and ultrastructure. Overall, the results suggest that Eulophia gracilis protected against BZ-induced hepatic oxidative damage and haematological disturbance in rats.

Інтоксикація бензолом

Бензол є представником групи ароматичних вуглеводнів і належить до групи кров’яних отрут, що викликають пригнічення кістковомозкового кровотворення з розвитком гіпопластичної або апластичної анемії. При впливі бензолу можуть розвиватися гострі та хронічні інтоксикації. У виробничих умовах проникнення бензолу і його гомологів в організм людини можливе через легені і неушкоджену шкіру. Симптоматика змін нервової системи і кістковомозкового кровотворення при гострому і хронічному впливі бензолу розрізняється. Гостра інтоксикація проявляється симптоматикою ураження центральної нервової системи із явищами загальних мозкових порушень, аналогічних до отруєння речовинами, що мають наркотичні властивості. Хронічна інтоксикація розвивається повільно, непомітно для хворого і характеризується ураженням кісткового мозку з порушенням процесів утворення клітин крові. Атиповою формою хронічної бензольної інтоксикації є розвиток бензольного лейкозу. Тому бензол відноситься до групи промислових канцерогенів. Типові форми гострої і хронічної бензольної інтоксикації неважко розпізнати. Для встановлення діагнозу бензольної інтоксикації насамперед необхідно мати дані, що підтверджують контакт хворого з бензолом. Важливе значення мають повторні дослідження периферичної крові, пункція кісткового мозку. Специфічних антидотів при бензольній інтоксикації немає. Проводиться симптоматичне лікування. Тому важливе значення має профілактика розвитку бензольної інтоксикації на виробництві до стадії виникнення глибоких необоротних порушень.

Magnetic molecularly imprinted polymers for extraction of S-phenylmercapturic acid from urine samples followed by high-performance liquid chromatography.

In this study, magnetic molecularly imprinted polymers (MMIPs) were prepared and used as sorbents for extraction of S-phenylmercapturic acid (S-PMA) from urine samples, followed by high-performance liquid chromatography ultraviolet-visible (HPLC-UV/Vis) analysis. The MMIPs were synthesized by the copolymerization reaction of (phenylthio) acetic acid (template molecule), methacrylic acid (functional monomers) and ethylene glycol dimethacrylate (cross-linkers). The morphology, structure property and surface groups of the prepared MMIPs were characterized by scan electron microscopy, transmission electron microscopy, infrared spectroscopy, X-ray diffraction pattern, thermogravimetric analyses, Brunauer-Emmett-Teller and vibrating sample magnetometer. The selectivity of the MMIPs was investigated in the presence of interferents. Various parameters affecting the S-PMA extraction efficiency were investigated, including MMIPs amount, pH, sample volume, desorption solvent, as well as extraction and desorption time. The obtained optimal parameters were as follows: MMIPs amount (20 mg), pH (3.0), sample volume (5mL), desorption solvent (methanol/acetic acid [9/1, v/v]), extraction time (30 minutes) and desorption time (2minutes). The method was validated according to the Food and Drug Administration Guidance for Industry on Bioanalytical Method Validation. The calibration curve for the analyte was linear in the concentration range of 0.030-1.0mg/L (r=0.9995). The LOD and LOQ of the method were 0.0080 and 0.0267 mg/L, respectively. The enrichment factor of the MMIPs was 5. The relative standard deviations of intra- and inter-day tests were in the range of 3.8-5.1% and 3.9-6.3%, respectively. The recoveries at three different concentrations of 0.10, 0.50 and 0.80 mg/L ranged between 95.2% and 98.6%. In addition, the MMIPs could be reused for at least eight times. The proposed method was successfully applied to the determination of S-PMA in urine samples. In addition, this developed method could be used as a tool in the early screening and clinical diagnosis of benzene intoxication.

A monoterpene antioxidant, linalool, mitigates benzene-induced oxidative toxicities on hematology and liver of male rats

ABSTRACT Benzene is a volatile chemical implicated in leukemia and hepatic injury through oxidative stress-mediated mechanism. Linalool is a naturally small molecular monoterpene with proven antioxidant properties. This study was carried out to investigate the potential role of Linalool in ameliorating the oxidative stress-mediated hematologic and hepatic dysfunctions by Benzene in rats. Hepatic injury and hematological imbalance were induced in Wister rats by intravenous administration of 0.2 mL of benzene solution every other days for 3 consecutive weeks. Following benzene intoxication, 40 mg/kg linalool was post-administered each day orally for two weeks. Hematological alteration was assessed by comparing the hematological parameters of control and benzene-exposed animals with or without linalool supplementation. Plasmal activities of liver biomarker enzymes (ALT, AST, and ALP), total thiol and advanced oxidation protein products (AOPPs) along with hepatic activities of SOD, CAT, and hepatic contents of thiol-reduced glutathione (GSH), malondialdehyde, and percentage DNA fragment were measured. Linalool showed improvements in liver functions and restored altered hematology, decreased levels of AOPPs and oxidative stress and mitigated genotoxicity affected by benzene. In conclusion, linalool exerted its organ protective and myeloprotective effect through its influence on antioxidant defense system and reduction of oxidative stress.

Preventive and Curative Effects of Atriplex Halimus L. Aqueous Extract on Benzene Provoked Hepatic Injury in Rats

Objective: The present study was designed to estimate the preventive and curative potency of aqueous extract of Atriplex halimus L. (Ah) aerial parts against benzene (BZ) intoxication in liver rats.
 Methods: 30 male albino rats were divided into five groups of 6 rats each: Control, Ah, BZ, AhP+BZ, and BZ+AhC. BZ (100 mg/kg b.w) was added in drinking water for 15 weeks. Aqueous extract of Atriplex halimus was received intragastrically during the last 30 days of BZ exposure for curative treatment (AhC) and all the duration of BZ exposure for preventive treatment (AhP). At the end the experiment, body weight gain and relative liver weight were estimated and liver enzyme markers (AST, ALT, ALP and LDH) were analysed by spectrophotometry. Histopathological studies on hepatic tissue were also performed by the method of Hematoxylin and Eosin staining.
 Results: Benzene administrated to rats caused an alteration in physiological parameters (body and organs weigh) and hepatic enzymes markers (AST, ALT, ALP and LDH). In addition, Histopathological studies showed a massive degeneration in liver tissue in BZ-exposed rats. However, treatment by Atriplex halimus especially preventive effect ameliorated most of the adverse effects induced by benzene. Ah restored the altered of physiological, biochemical and histopathological changes.
 Conclusion: The present study suggests that Atriplex halimus extract could be a substantially promising hepatoprotective agent against benzene toxic effects and may be against other hepatotoxic chemical or drugs.
 Keywords: Atriplex halimus, Benzene, hepatotoxicity, Rats.

Changes in the nervous system state and peripheral blood parameters under benzene intoxication during an experiment

Changes in the nervous system state and peripheral blood parameters under benzene intoxication during an experiment

Effect of exposure to Benzene on oxidative stress and the functions of liver and kidney of male Albino Rat

Aim: Benzene is a volatile organic compound known to be carcinogenic to humans. The present study was conducted to determine the effects of exposure to average indoor concentrations of benzene on liver and kidney of rats. Methods: Adult male albino Wistar rats were exposed to 10, 30 and 50 ppm of benzene for 14 days. The effect on lipid peroxidation (LPO), nitric oxide (NO) and glutathione (GSH) as oxidative markers, in addition, liver and kidney function levels were determined in adult male rats. Results: Benzene intoxication increased the activities of liver enzymes (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) and the bilirubin level, in addition to the levels of uric acid, urea and creatinine were increased in the serum. Moreover, benzene inhalation at 10, 30 and 50 ppm for 14 days in adult male rats enhanced LPO and NO production in both serum and liver with a concomitant reduction in GSH content. Conclusions: On the basis of the above results, it can hypothesis that benzene inhalation caused hepatic and renal damages even at low concentration.

Influence of acetylsalicylic acid on hematotoxicity of benzene

The aim of the study was to evaluate the influence of acetylsalicylic acid (ASA) on benzene hematotoxicity in rats. The study was carried out on rats exposed for 2, 4 and 8 weeks to benzene vapour at a concentration of 1.5 or 4.5 mmol/m(3) of air (5 days per week, 6 hours per day) alone or together with ASA at the doses of 5, 150 or 300 mg/kg body weight (per os). Benzene at a concentration of 4.5 mmol/m(3) caused a slight lymphopenia, granulocytosis and reticulocytosis in blood. In bone marrow traits of megaloblastic renewal, presence of undifferentiated cells and giant forms of granulocytes as well as an increase in myeloperoxidase and decrease in chloroacetate esterase activity and lipids content were noted. ASA (150 and 300 mg/kg b.w.) influenced some of hematological parameters, altered by benzene intoxication. ASA limited the solvent-induced alteration in blood reticulocyte count and in the case of bone marrow in the erythroblasts count. Traits of megaloblastic renewal in bone marrow were less pronounced. Besides, higher activity of myeloperoxidase and the decrease in the level of lipids in granulocytes were noted. Our results suggest that ASA limited the benzene-induced hematotoxicity.

Immuno-, phagocytosis-modulating and antitoxic properties of dipeptides are defined by the activity of their constituent amino acids

In experiments on mice and the influence in vitro of the dipeptides GluTrp, LysAsp, LysVal, AspGlu, GluAsp on their constituent amino acids and mixtures on the indexes of specific and non-specific resistance was studied. There is no difference between the dipeptides and their constituent amino acids (excepting Lys) neither in immune, phagocytosis modulating or antitoxic properties. Some amino acids (aspartic acid, glutamic acid, methionine and tryptophan) are promising for the effective prevention of diseases that develop as a result of chronic benzene intoxication.

Similarity of immunomodulating, phagocytosis-modulating, and antitoxic properties of dipeptides and their constituent amino acids

Immunomodulating, phagocytosis-modulating, and antitoxic properties of dipeptides depend on activities of their constituent amino acids. Some amino acids have considerable promise for efficient prevention of occupational diseases caused by chronic benzene intoxication.

Hematotoxic effects of benzene analyzed by mathematical modeling

The hematopoietic cell response to benzene intoxication in mice (during and after long-term inhalation) was analyzed by a mathematical model of murine hematopoiesis. Two complementary methods, Time-Curve and Steady-State Analysis, were developed to identify target cells for benzene toxicity and to quantify the extent of damage in different stages of development of these target cells. We found that (i) erythropoietic cells were the most sensitive; (ii) granulopoietic cells were about half as sensitive as erythropoietic and (iii) hematopoietic stem cells exhibited a sensitivity that ranged between that of erythropoietic and granulopoietic cells. A dose-response relationship between benzene levels and damage in target cells (valid from 1 to more than 900 ppm) was derived that was linear for doses up to 300 ppm and plateaued thereafter. This relationship indicated that benzene-induced hematotoxicity is subject to a saturable process. Recovery of hematopoiesis following chronic benzene intoxication was stimulated for different doses and preceding exposure periods. The impaired recovery following exposure periods > 8 weeks could be explained by a severe reduction in the maximum self-maintenance of stem cells. This study indicates that the present mathematical model represents a useful approach to investigate alternate hypotheses for the action of hematotoxic agents.

Modulation of benzene toxicity by polyinosinic-polycytidilic acid, an interferon inducer

Repeated intraperitoneal administration of benzene (1.0 ml/kg body wt.) for 3 days produced leucopenia, lymphocytopenia and significantly decreased body wt. ( P < 0.001) and organ weights of thymus ( P < 0.001) and spleen ( P < 0.001) in female albino rats. Total iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly increased as a result of benzene exposure. Low molecular weight (LMW) bleomycin detectable iron content was accumulated in bone marrow, whereas hepatic LMW iron was not detectable after benzene intoxication to rats. Prior administration of single dose (250 μg/100 g body wt.) of Poly IC, an interferon inducer with immunomodulating potential was found to be ameliorate some of the adverse effects of benzene as well as restoration of hepatic architecture histologically. Superoxide dismutase activity, lipid peroxidation, total iron content and LMW iron content (bone marrow) were normalised. Pretreatment of animals with Poly IC was able to enhance the SRBC antibody titre in benzene-treated animals. This study suggests that the beneficial effects of Poly IC in the amelioration of the acute toxicity of benzene has clinical significance.

A laboratory method of making detector tubes for the determination of benzene concentration in the exhaled breath

Abstract The parent aromatic hydrocarbon, benzene, has been and still is used in industry on a large scale, although the use of it is generally avoided because of its adverse health effects. Hence, it is still possible to come across a number of benzene intoxication cases, due to its technically inappropriate way of use. It has been reported that the amount of absorption of benzene can be estimated by providing certain parameters, such as benzene in the inspired air and exhaled breath. The gaschromatographic methods used in the determination of these parameters seems to be accurate and highly specific, but needed time‐consuming pre‐arrengements and expesive apparatus not generally available in working places. Therefore, a practicable semi‐quantitative method was needed for screening tests to estimate the degree of exposure to benzene vapour. For this purpose, a laboratory method of making a colour indicator tube was developed for determination of benzene concentration in the exhaled breath. This tube is sensitive enough to determine benzene in breath down to 2 ppm. Benzene concentrations can be determined without being affected by up to 30 ppm of toluene. Xylene and cumene have no influence at all on the determination. The tube ca also be modified to determine atmospheric levels of benzene in the working environment.

Effect of blockers of protein and oligopeptide synthesis on self stimulation

Cellular immunity and activity of enzymes of xenobiotic metabolism have been investigated. It has been shown that administration of benzene induces a stable immune deficiency syndrome characterized by a decrease in the quantity if antibody-forming cells, T-killers and T-suppressors. The activity of enzymes (cytochrome P-450 and cytochrome C reductase) was also inhibited. It has been shown that anabol can stimulate the parameters of cellular immunity and enzyme activity. Benzene intoxication was demonstrated to be a model of immune deficiency syndrome similar to the clinical pattern. Anabol was shown to be an effective immunomodulator.

Petit mal and grand mal seizures produced by toluene or benzene intoxication in the cat

Motor incoordination, euphoria and hallucinations are symptoms reported for humans voluntarily intoxicated by industrial solvents. An epileptic-like consciousness impairment has also been noted. The present paper describes a technique used for the experimental study of solvent intoxication in which toluene and benzene can be applied directly into the trachea of freely moving cats with chronically implanted electrodes. This technique permits the control of solvent dose and time of exposure. Results showed a 3 Hz spike-wave activity in the gyrus cinguli recording with both toluene or benzene intoxication. Furthermore, benzene inhalation produced generalized tonic-clonic seizures. These effects were dose related. However, a sensitization period was essential for the development of such alterations, and effects showed a tendency to shortening through chronic exposures. These alterations were correlated with behavioral disturbances such as nodding, twitching and apparent hallucinations. Results are discussed regarding the sensitization period, the optimal peak of effects, and the period of tolerance development relevant to an earlier found amygdalar activation that could be correlated with other methods inducing experimental seizures, such as repetitive stimulation of the brain (kindling).

The behaviour of some enzymes in the mouse liver due to chronic benzene intoxication

1. Long trem benzene action brings about a permanent decrease in oxidoreductive enzymes and active transport as well as an inactivation of the lysosomal apparatus in liver-cells. 2. Particular liver lobule zones show different sensitivity to toxic action of benzene which might result from their different role in the processes of benzene biotransformation.

Histochemical and histoenzymatic changes in mouse liver in subacute benzene intoxication

The investigations were performed on mice. They were divided into a control group and 4 experimental groups. The experimental animals were administered intraperitoneally benzene 6 X every 24 h. The animals were decapitated 30 min. 4, 12 and 24 h after the last benzene administration. During the experiment, dyeing for neutral lipids and glycogen was carried out, and the activity of NADH2-r.t., SDH, G-6-Pase, ATP-ase and ACP was estimated. A decrease of glycogen content in liver cells, deviations in the amount of neutral lipids, reversible decrease of mitochondrial enzymes activity, and intensification of the processes of intracellular catabolism were found.

Effects of benzene vapour on the γ-aminobutyric acid (GABA) system in rat brain

Chronic benzene intoxication (0.35 mg/l) initially caused an increased in GABA concentrations with a simultaneous decrease in the glutamic and aspartic acid levels in cerebellum and pons Varolii of rats. On the 14th day of chronic exposure the level of all three amino acid was increased and associated with a depressive character of EEG patterns throughout the cerebellum, pons Varolii, and the sensori-motorial region of the cerebral hemispheres. On the 30th day, the GABA level had almost returned to its initial level but concentrations of glutamic and aspartic acid were decreased by more than 60% in cerebellum and by 20% in pons Varolii. During acute benzene poisoning (35.0 mg/l, for 15 min) the level of GABA was increased 5–6 times above the normal values. A 45% increase in the GABA level and a decreased amount of glutamic and aspartic acid were still observed 48 hr after the cessation of benzene inhalation. GAD activity in cerebellum and pons Varolii, during acute and chronic benzene intoxication, was higher than that of untreated animals: it was greater on the 14th day of chronic intoxication, 5- and 2-fold, respectively, and 4- and 3-fold at the 15th minute of acute intoxication. The GABA-T activity was also increased in these two structures (4–5-fold) by low and high concentrations of benzene vapour.

The dynamics of histoenzymatic changes in the kidney in acute poisoning with benzene

The experiments were carried out in mice which were divided into 4 experimental groups and a control group. In the course of the experiment SD, NADH2-tetrazolium reductase; ATP-ase, G-6-P-ase and AP were observed. It was found that acute benzene intoxication causes the disturbances in the enzymatic activities of the cells of the main segment of the nephron. The impairment of tissue respiration and oxygen phosphorylation and of active transport is due to benzene intoxication. Benzene leads to injury of the endoplasmatic reticulum in the cells of the kidney.