Antihematotoxic Role of Bunium persicum Seed Differential Extracts in Animal Model: Reactive Oxygen Species Might Be a Contributor

Tahir Ali,Kamran Saeed,Muhammad Abdullah,Iram Murtaza 질병관리본부 2014 Osong Public Health and Research Persptectives Vol.5 No.6

Objectives: Humans have been using plants as natural medicines since prehistoric times. Bunium persicum is a rich source of oils with different biological activities such as antioxidative and antimicrobial activities. The aim of this study is to evaluate the antihematotoxic and antioxidative effects of the differential extracts of B. persicum against leukemic blood induced hematotoxicity in an animal model. Methods: This study was performed on animals, which were divided into several groups: normal control, disease control, and groups that were administered with differential extracts of plants. We measured the concentration of free radical [reactive oxygen species (ROS)] and hematological parameters as blast cells from the tibia and femur in different groups. Results: The ROS level and blast cells count were higher in disease control groups than in groups treated with varying amounts of B. persicum extract and the normal group. Moreover, there was an imbalance in hematological parameters in untreated and treated groups with a correlation between free radicals and plant extract administration. Conclusion: These findings may indicate a possible link between free radicals and hematotoxicity and blast cells, while depicting a potential therapeutic role for B. persicum against ROS-induced hematotoxicity.

Differential Gene Expression Profiling in Human Promyelocytic Leukemia Cells Treated with Benzene and Ethylbenzene

Sarma, Sailendra Nath,Kim, Youn-Jung,Ryu, Jae-Chun The Korean Society of Toxicogenomics and Toxicopro 2008 Molecular & cellular toxicology Vol.4 No.4

Benzene and ethylbenzene (BE), the volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Chronic exposure of benzene is responsible for myeloid leukemia and also ethylbenzene is also recognized as a possible carcinogen. To evaluate the BE effect on human, whole human genome 35 K oligonucleotide microarray were screened for the identification of the differential expression profiling. We identified 280 up-regulated and 201 down-regulated genes changed by more than 1.5 fold by BE exposure. Functional analysis was carried out by using DAVID bioinformatics software. Clustering of these differentially expressed genes were associated with immune response, cytokine-cytokine receptor interaction, toll-like signaling pathway, small cell lung cancer, immune response, apoptosis, p53 signaling pathway and MAPKKK cascade possibly constituting alternative or subordinate pathways of hematotoxicity and immune toxicity. Gene ontology analysis methods including biological process, cellular components, molecular function and KEGG pathway thus provide a fundamental basis of the molecular pathways through BEs exposure in human lymphoma cells. This may provides a valuable information to do further analysis to explore the mechanism of BE induced hematotoxicity.

Lack of connexin 32 does not enhance the benzene-induced hematotoxicity and hemopoietic tumor incidence in mice

Yoon, Byung-IL The Korean Society of Veterinary Science 2005 大韓獸醫學會誌 Vol.45 No.4

This study was performed to evaluate using wild-type (WT) and $C{\times}32$ knockout (KO) mice if lack of cell to cell communication by connexin 32 gap junction enhances the benzene-induced hematotoxicity and hemopoietic tumor development. The WT and $C{\times}32$ KO mice were exposed to 300 ppm of benzene for 6 hours/day, 5 days/week for a total of 26 weeks by inhalation, and then sacrificed to evaluate the toxicities of hemopoietic organs or allowed to live out their life span to evaluate the hemopoietic tumor incidence. The significant increase and decrease of organ weight were respectively noted in spleen and thymus of both WT and $C{\times}32$ KO mice without significant difference between the genotypes. Histopathologically, benzene exposure for 26 weeks induced the morphological changes in hemopoietic organs, characterized by fat cell accumulation in the bone marrow and extramedullary hemopoiesis in the spleen. The fat cell accumulation was, compared with that of WT mice, considerably exacerbated in the $C{\times}32$ KO mice. However, no significant difference was observed in the changes of hematological values and bone marrow cellularity as well as in the onset and incidence of hemopoietic tumors between WT and $C{\times}32$ KO mice. In conclusion, this study indicated little significant role of the cellular communication by $C{\times}32$ gap junction in the action mechanism of benzene hematotoxicity and leukemogenicity.

Fluted Pumpkin (Telfairia occidentalis) protects against phenyl hydrazine-induced anaemia and associated toxicities in rats

Oladele Johnson O.,Oyeleke Oyedotun M.,Awosanya Olaide O.,Olowookere Boyede D.,Oladele Oluwaseun T. 경희대학교 융합한의과학연구소 2021 Oriental Pharmacy and Experimental Medicine Vol.21 No.4

Xenobiotics have been documented to play crucial role in pathogenesis of human diseases. Phenyl hydrazine administration has been associated with hematotoxicity by altering iron metabolism and activating immune response. Telfaria occidentalis is a medicinal plant rich in phytochemicals and minerals that are immune boosters. This study investigated the effect of ethanol leaf extract of T. occidentalis against phenyl hydrazine induced anaemia and associated toxicities in rats. Phenyl hydrazine was exposed to rats through oral administration and ethanol leaf extract of T. occidentalis or vitamin E was administered to ameliorate the toxic effect of the toxicant. This was followed by evaluation of haematological parameters, body weight, and serum protein biomarkers like bilirubin, albumin, total bilirubin. Phenyl hydrazine induced anaemia with significant reduction of blood components like haemoglobin, erythrocytes, leukocytes with concomitant reduction in the body weight of the rat compared to the control. Phenyl hydrazine also compromised serum protein homeostasis as evidenced by elevated serum total protein, albumin, bilirubin and globulin levels. Nevertheless, treatment with ethanol leaf extract of T. occidentalis modulates all the anomalies suggesting its ameliorating effects against phenyl hydrazine-induced anaemia, and may be useful in the treatment/management of chemically induced anaemia or other related diseases.

Benzene-Induced Hematotoxicity and Myelotoxicity by Short-Term Repeated Oral Administration in Mice

Jung-Yeon Yi,Byung-Il Yoon 한국실험동물학회 2008 Laboratory Animal Research Vol.24 No.1

Exposure dose of benzene has been postulated to be critical to induce hemopoietic malignancies. By long-term inhalation of benzene, 300 ppm has been shown to be the dose that induces high frequency of leukemia with the least animal mortality in the mouse. With regard to the benzene studies, determination of the oral dose that will be corresponding to the critical inhalation dose could be important to design the experimental protocol based on oral administration. Based on the background data such as the respiratory volume, absorption factor, and so on, we, therefore, calculated a potential oral dose that is expected to be corresponding to 300 ppm of inhalation dose. The determined oral dose was 150 ㎎/㎏ B.W. We then evaluated, using C57BL/6 mice, the toxic effects of benzene on the peripheral blood and the bone marrow (BM) by oral administration of the selected dose once a day for 1 and 2 weeks. Leukocyte, red blood cell number and BM cellularity were respectively decreased to 47.8%, 72.3% and 66.7% of the respective control level by 1-week oral administration of benzene, and to 30.8%, 60.2% and 80.2% by 2-week oral administration. Changes in the leukocyte numbers were mainly due to the marked decrease of lymphocytes. According to the results, the changes of the parameters examined were generally corresponding to the change levels by the 2-week inhalation. In conclusion, the selected dose, 150 ㎎/㎏ B.W., was a reliable dose corresponding to the 300 ppm benzene inhalation, which was verified by in vivo mouse study.

SD랫드에서 다이아지논의 경구노출에 의한 급성 혈액독성

박상정,김수현,김선겸,이상인,박연기,유아선,정상희 한국농약과학회 2019 농약과학회지 Vol.23 No.3

Diazinon (DZN), a representative organophosphorus pesticide, is produced more than 500 tons per year in Korea and induces neurotoxicity by inhibition of acetylcholine esterase. However, information of hematotoxicity is limited. To investigate the effect of single exposure of DZN on blood cells and composition, a single oral dose with DZN 15 and 150 mg/kg bw was treated to 8 weeks old SD male rats, and then whole blood and urine were collected at 1, 4, 8 and 24 hours after administration. For collected blood samples at each time, red blood cell counts, white blood cell counts, hematocrit and hemoglobin were tested and microscopic examination of stained blood cells was performed. And for collected urine at each time, the occult blood, white blood cells and etc. were screened. As a result, red blood cell counts and hemoglobin increased slightly at 4 hours by both doses of DZN, and hematocrit was significantly increased at 4 hours by DZN 150 mg/kg bw. Total leukocyte counts were not significantly changed However, neutrophils were decreased at 1 hour by DZN 15 mg/kg bw, also at 1 and 8 hours decreased after administration of DZN 150 mg/kg bw. Lymphocytes were significantly increased at 8 hours by DZN 150 mg/kg bw. MCV were significantly increased at 1 hour by DZN both doses and then recovered. MCH were slightly but significantly increased by DZN 150 mg/kg bw at 1 hour. Microscopic examination showed that DZN induced abnormal white blood cells and leukocyte positive reaction was observed in urine from 1 hour to 24 hours. In conclusion, DZN induces hematological toxicity such as neutropenia, abnormal leukocyte appearance and detection of leukocytes in urine by single oral exposure in rats, which indicates immunity weakness and consequantly vulnerability to infection. 다이아지논(Diazinon, DZN)은 대표적인 유기인계 살충제로, 국내에서 연간 500톤 이상 생산되며 신경독성등을 유발하는 것으로 알려져 있으나 혈액독성에 대한 정보는 부족한 실정이다. 본 연구에서는 DZN 단회노출이 혈액세포 및 조성에 미치는 영향을 알아보고자 8주령 SD랫드에 15, 150 mg/kg bw의 용량으로 단회 강제 경구투여 후1시간, 4시간, 8시간 및 24시간 후에 혈액 및 뇨를 채취하여 혈액 중 적혈구수, 백혈구수, 헤마토크리트수치, 헤모글로빈 및 백혈구분획 검사와 혈액세포에 대한 현미경 검사를 실시하고, 뇨에 대하여 잠혈, 백혈구수 등에 대한 스크리닝을 실시하였다. 그 결과 무처치군의 혈액에 비하여 DZN 15, 150 mg/kg bw에 의해 적혈구수와 헤모글로빈이 4시간째에 약하게 증가하는 경향이었으며, 헤마토크리트수치는 DZN 150 mg/kg bw에 의해 4시간째에 유의하게 증가하였다. 총백혈구수는 DZN 15 및 150 mg/kg bw 투여시 유의한 변화는 없었으나, 호중구수가 DZN 15 mg/kg bw 투여후 4시간째에 유의하게 감소하였으며, DZN 150 mg/kg bw 투여 후 1시간 및 8시간째에 유의하게 감소하였다. 림프구는 DZN 150 mg/kg bw 투여시 8시간째에 유의하게 증가하였다. MCV는 15, 150 mg/kg bw에 의해 투여 후 1시간째 유의하게 증가하였으나 이후 회복하는 경향이었다. MCH는 150 mg/kg bw 투여 후 1시간째 미약하나 유의하게증가하였다. 혈액세포에 대한 현미경적 검사 결과 혈구에서 DZN 15, 150 mg/kg bw 투여 후 1시간부터 24시간째까지 지속적으로 이상백혈구 출현율이 증가하였으며, 뇨에서는 백혈구 양성반응이 확인되었다. 결론적으로 DZN은 랫드에 단회 경구투여시 호중구의 감소와 이상백혈구 출현 및 뇨중 백혈구가 검출되는 등의 혈액독성이 유발되며, 이로써DZN 급성노출시 면역기능이 약화될 수 있고, 감염에 취약하게 되어 2차 질병에 노출될 수 있을 것으로 판단되었다.