TOXICOLOGY
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2025
·
IF 4.6
Jin Zhou,Pinpin Sui,Jianxin Zhao,Xiurong Cheng,Tao Yu,Shiwei Cui,Xiangrong Song,Caihong Xing
Patients with benzene-induced leukemia undergo a continuous transformation from myelosuppression to malignant proliferation. However, the underlying mechanisms in this process remain unknown. Our previous studies have shown that the pathways involved in self-renewal capacity of bone marrow (BM) cells in Mll-Af9 mice exposed to benzene for life are significantly activated after severe blood toxicity. In order to investigate the hematotoxicity effects of benzene on the self-renewal capacity of HSCs, Mll-Af9 chimeric mice were exposed to benzene and hematological parameters were dynamically monitored after benzene exposure. Transcriptomic analysis were used to analyze different time points during benzene exposure and after competitive bone marrow transplantation (BMT). Results showed that despite severe hematotoxicity in mice, but the chimerism rate of Mll-Af9 cells in peripheral blood (PB) cells was significantly increased after 10 weeks benzene exposure ( P < 0.001). After competitive BMT, the chimerism rate of Mll-Af9 cells from 10 weeks benzene-exposed mice was gradually increased and significantly surpassed that of the control at 26 weeks of bone marrow reconstruction (benzene group 86 % VS control group 78 %, P = 0.03). Transcriptome analysis revealed that the expression levels of self-renewal related genes, such as Hox genes ( Hoxb4 , Hoxa7 , Hoxa10 ), Mecom and Ms4a in BM cells of 10 weeks benzene-exposed mice were relatively higher compared to those in the control group, but no significant difference were observed. Interestingly, Hoxa7 , Hoxa10 and Mecom were significantly up-regulated at 26 weeks after bone marrow transplantation. In conclusion, our study suggests that abnormal expression of self-renewal-related genes may be potential early biomarkers for benzene-induced hematotoxicity. This hematotoxicity may contribute to the acquisition of evolutionary advantages by leukemic precursor cells and accelerate malignant transformation.
研究领域:
血液学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Rongfang Yang,Jiaxin Zhang,Xiumei Xing,Shiyuan Zhong,Wenxue Li,Lixian Wen,Yuwei Zhang,Hongwei Zhou,Shen Chen,Wen Chen,Yongmei Xiao,Liping Chen
Benzene exposure has been linked to various adverse health effects. However, the effective strategy for prevention or treatment of benzene-induced hematotoxicity remains unsolved. We previously administrated hepatocyte-specific deletion of Ppp2r1a gene (encoding PP2A Aα subunit) mice with benzene via inhalation for 28 days, and found homozygote (HO) mice exhibited alleviative hematotoxicity compared with wild type (WT) mice. Here, we integrate untargeted metabolomics and transcriptomics data to identify the key metabolic pathways and metabolites attenuating benzene-induced hematotoxicity. Metabolomics analysis revealed the perturbation of nicotinate and nicotinamide metabolism, as well as taurine and hypotaurine metabolism pathways, were implicated in regulating benzene-induced hematotoxicity. Meanwhile, transcriptome analysis showed that immune-, inflammation-, and metabolism-related pathways were obviously disturbed in WT mice groups upon benzene exposure, while sirtuin signaling pathway, associated with nicotinate and nicotinamide metabolism, was activated in HO mice groups. Notably, combined metabolomics and transcriptomics analysis further confirmed the involvement of nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism pathways in relieving benzene-induced hematotoxicity. Specific metabolites, including 1-methylnicotinamide (MNA), nicotinamide (NA), β-nicotinamide mononucleotides (NMN), and taurine were identified as the potential metabolites alleviating benzene-induced adverse effects. In vitro experiments demonstrated the protective effect of MNA and NA against 1,4-benzoquinone (1,4-BQ)-caused cytotoxicity in HL-60 cells. In vivo , MNA supplementation in drinking water could effectively restore the decline in white blood cell (WBC), lymphocyte (LYMPH), and reticulocyte (RET) counts, also mitigate oxidative damage and genotoxicity in response to benzene exposure. These observations highlight the potential of MNA supplementation as a strategy for preventing benzene-caused hematotoxicity.
研究领域:
毒理学
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代谢组学
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分子生物学
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DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2021
·
IF 2.73
Yang Liu,Hua Fu,Li Zuo
Background Angiogenesis and inflammation exhibit a mutually reinforcing relationship in many human diseases. Vascular endothelial growth factor (VEGF) is one of the most important proangiogenic mediators. Conbercept is a novel VEGF inhibitor.Method Type II collagen-induced rat rheumatoid arthritis (CIA) model was established to evaluate the anti-chronic inflammation activities of Conbercept. ELISA was used to measure the concentrations of immune factors in the blood of arthritis rats. The xylene-induced ear edema was conducted to evaluate the effect of Conbercept on acute inflammation.Result and discussion Our results showed that Conbercept significantly reduced the paw edema volume and the arthritis index in CIA rats. Furthermore, we found that Conbercept decreased the serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in CIA rats. Xylene-induced ear edema is a widely used method to study acute inflammation. Conbercept significantly inhibited xylene-induced ear edema.Conclusion All results indicate that Conbercept exhibits significant inhibition of acute and chronic inflammation.
研究领域:
药理学
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免疫学
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风湿病学
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DOI
PubMed
高影响因子
Letters in Drug Design & Discovery
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2019
·Vol. 16
·期 9
·1020-1030
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IF 0.953
Liang Zhaochang,Huang Yuping,Wang Shiben,Deng Xianqing
Background: Several series of pyrazole derivatives containing (thio) semicarbazide (4a-4h, 5a-5l, 6a-6f, 7a-7c) were designed and synthesized to screen dual inflammatory and antimicrobial activities. Methods: The products were characterized by1H NMR, 13C NMR and HRMS. In vitro
LPS-induced TNF-α model and in vivo xylene-induced ear-edema model were used to evaluate their antiinflammatory activity. Their in vitro antimicrobial activities were evaluated using a serial dilution method against several gram-positive strains, gram-negative strains and a fungi strain.
Results: Bioassays indicated that most of the compounds markedly inhibited the expression of TNF- α at the concentration of 20 μg/mL Compounds 5i, 6b, and 7b had comparable in vivo antiinflammatory activity to the reference drug dexamethasone at the dose of 50 mg/kg. In addition,
several compounds showed antimicrobial activity against different strains, and compounds 5g and 5h exhibited potent inhibitory activities with the MIC value of 8 μg/mL against the Streptococcus pneumoniae CMCC 31968 and Staphylococcus aureus CMCC 25923, respectively. Compound 7b, which
exhibited both anti-inflammatory and antimicrobial activities, should be studied as it is or after derivatization. Conclusion: It can be concluded that pyrazoles, with (thio)-semicarbazone moieties, have the potential to be developed into new anti-inflammatory agents.
研究领域:
药理学
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药物化学
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传染病学
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炎症研究
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DOI
高影响因子
Asian Pacific Journal of Tropical Biomedicine
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2015
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IF 0
Raphael Nammahime Alolga,Sarah Wambui Amadi,Vitus Onoja,Assogba Gabin Assanhou,Moses Muyaba,Said Abasse Kassim
Objective To evaluate the scientific basis for the use of Kang 601 heji (K-601) as an anti-inflammatory and antipyretic agent using appropriate animal models. Methods Carrageenan-induced rat paw and xylene-induced ear oedemas were models used to investigate anti-inflammatory actions of K-601. Lipopolysaccharide-induced pyrexia model was used to evaluate antipyretic activity in Wistar rats. The anti-inflammatory and antipyretic mechanisms were evaluated by detecting prostaglandins E 2 , nitric oxide, interleukin-1β and tumour necrosis factor-α levels using appropriate reagents and ELISA kits. Results The results revealed that K-601 reduced the level of inflammations in both anti-inflammatory models in a dose-dependent manner. The same was true for the antipyretic model. The possible mechanisms of actions were through the inhibition of prostaglandins E 2 , interleukin-1β, tumour necrosis factor-α and nitric oxide. Conclusions K-601 has proven anti-inflammatory and antipyretic actions. The findings provide a scientific basis for the use of K-601 as anti-inflammatory and antipyretic agent in traditional Chinese medicinal practice.
研究领域:
药理学
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中医药学
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炎症研究
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免疫学
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DOI
PubMed
JOURNAL OF ETHNOPHARMACOLOGY
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2023
·
IF 5.4
Jiameng Zhang,Yanfang Wu,Chenyu Wang,Weidong Xu,Zichen Zhang,Suya Zhang,Xinyi Guan,Xinsheng Wang
Ethnopharmacological relevance Syringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa . Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis. Aim of the study: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro . The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. Methods HPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and β-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro . The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo . The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo . In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1β) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. Results HPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1β were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. Conclusion The study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.
研究领域:
药理学
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民族药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2019
·Vol. 29
·期 1
·46-53
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IF 1.754
Peng Wei,Han Ping,Yu Luyao,Chen Ying,Ye Bingzhu,Qin Luping,Xin Hailiang,Han Ting
The fruits of Xanthium strumarium L., Asteraceae, have been used for various diseases in Chinese folk medicine, including allergic rhinitis, tympanitis, arthritis, ozena etc. The current study was aimed to investigate the therapeutic effects of caffeoylquinic acids from fruits of X. strumarium on allergic rhinitis in animals. The toxicity test indicated that the caffeoylquinic acids have no obvious toxicity. By using HPLC assays combined with reference standards, ten caffeoylquinic acids were identified as the predominant constituents. Anti-allergic activities of the caffeoylquinic acids were evaluated using passive cutaneous anaphylaxis test and Schultz-Dale test; dimethylbenzene induced ear edema test was performed to evaluate its anti-inflammatory effect. Then, the allergic rhinitis model in rats was established to evaluate the therapeutic effects of the caffeoylquinic acids against allergic rhinitis with the following indexes: allergic rhinitis symptom scores, serum levels of pro-inflammatory cytokines, histopathological examination, and histamine release. Our study revealed that the caffeoylquinic acids showed obvious anti-allergic and anti-inflammatory properties, and its treatments were beneficial for ameliorating the nasal symptoms, decreasing pro-inflammatory cytokines, and inhibiting the releases of histamine. Collectively, the caffeoylquinic acids might be utilized as effective and safe disease therapeutic agents for allergic rhinitis.
研究领域:
药理学
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免疫学
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过敏
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植物化学
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产品关联
DOI
高影响因子
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