JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
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IF 6.2
Mengyuan Qi,Shengjin Zhang,Hua Fang,Yunlong Yu,Junsheng Liu,Luqing Zhang
This study investigates the combined effects of polystyrene nanoplastics (PS-NPs) and deltamethrin (DEL) on mice, focusing on their different impacts among organs. Mice were exposed to PS-NPs and/or DEL for 30 days. Results showed that PS-NPs alleviated DEL-induced oxidative damage in the liver and kidney by reducing its accumulation due to decreased bioaccessibility. Conversely, PS-NPs increased DEL accumulation in the intestine, leading to enhanced susceptibility to enteric infections caused by bacteria, viruses, and parasites, as indicated by transcriptomic analysis. PS-NPs delayed DEL excretion by reducing gastrointestinal motility, as evidenced by altered neurotransmitter levels, thereby contributing to greater intestinal accumulation of DEL. Moreover, 16S rDNA sequencing revealed that PS-NPs tended to decrease beneficial bacteria and increase pathogenic bacteria in the gut microbiota, further heightening susceptibility to enteric infections upon coexposure. The findings of this study shed new light on the complex health risks associated with coexposure to nanoplastics and pesticides.
研究领域:
毒理学
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环境科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
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IF 6.6
Ling Wang,Fangqing Cai,Yixuan Li,Xiaolan Lin,Yuting Wang,Weijie Liang,Caiyu Liu,Cunze Wang,Junshan Ruan
Purpose Renal cell carcinoma (RCC) is the most common and lethal type of urogenital cancer, with one-third of new cases presenting as metastatic RCC (mRCC), which, being the seventh most common cancer in men and the ninth in women, poses a significant challenge. For patients with poor prognosis, temsirolimus (TEM) has been approved for first-line therapy, possessing pharmacodynamic activities that block cancer cell growth and inhibit proliferation-associated proteins. However, TEM suffers from poor water solubility, low bioavailability, and systemic side effects. This study aims to develop a novel drug formulation for the treatment of RCC.Methods In this study, amphiphilic block copolymer (poly(ethylene glycol) monomethyl ether-poly(beta-amino ester)) (mPEG-PBAE) was utilized as a drug delivery vehicle and TEM-loaded micelles were prepared by thin-film hydration method by loading TEM inside the nanoparticles. Then, the molecular weight of mPEG-PBAE was controlled to make it realize hydrophobic–hydrophilic transition in the corresponding pH range thereby constructing pH-responsive TEM-loaded micelles. Characterization of pH-responsive TEM-loaded nanomicelles particle size, potential and micromorphology while its determination of drug-loading properties, in vitro release properties. Finally, pharmacodynamics and hepatorenal toxicity were further evaluated.Results TEM loading in mPEG-PBAE increased the solubility of TEM in water from 2.6 μg/mL to more than 5 mg/mL. The pH-responsive TEM-loaded nanomicelles were in the form of spheres or spheroidal shapes with an average particle size of 43.83 nm and a Zeta potential of 1.79 mV. The entrapment efficiency (EE) of pH-responsive TEM nanomicelles with 12.5% drug loading reached 95.27%. Under the environment of pH 6.7, the TEM was released rapidly within 12 h, and the release rate could reach 73.12% with significant pH-dependent characteristics. In vitro experiments showed that mPEG-PBAE preparation of TEM-loaded micelles had non-hemolytic properties and had significant inhibitory effects on cancer cells. In vivo experiments demonstrated that pH-responsive TEM-loaded micelles had excellent antitumor effects with significantly reduced liver and kidney toxicity.Conclusion In conclusion, we successfully prepared pH-responsive TEM-loaded micelles. The results showed that pH-responsive TEM-loaded micelles can achieve passive tumor targeting of TEM, and take advantage of the acidic conditions in tumor tissues to achieve rapid drug release.
研究领域:
药学
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纳米技术
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Shuqin Lu,Qingsong Yuan,Lulu Wang,Dapeng Su,Min Hu,Lanping Guo,Chuanzhi Kang,Tao Zhou,Jinqiang Zhang
Ethnopharmacological relevance The Radix Dipsaci , a traditional Chinese medicine with a history spanning over 2000 years in China, is widely recognized for its hepatorenal tonic properties, musculoskeletal fortifying effects, fracture healing capabilities, and its frequent application in the treatment of osteoporosis. Like many traditional Chinese herbal medicines, preparations from Radix Dipsaci are at risk of contamination by harmful mycotoxins such as aflatoxin B1. Aims of the study This study aims to evaluate the impact of aflatoxin B1 contamination on Radix Dipsaci in terms of changes in quality, efficacy of anti-osteoporosis and hepatorenal toxicity. Materials and methods The contamination rates and levels of major mycotoxins were determined in 45 batches of Radix Dipsaci samples using UPLC-MS/MS analysis. The total saponin content and the levels of akebia saponin D in Radix Dipsaci and its decoctions were evaluated through high-performance liquid chromatography (HPLC) analysis. Differences in secondary metabolites between samples without any mycotoxin contamination (N-RD) and those contaminated solely by aflatoxin B1 (AFB1-RD) were compared using metabolomics sequencing and analysis. The anti-osteoporotic efficacy of Radix Dipsaci contaminated with aflatoxin B1 was assessed in a murine model of retinoic acid-induced osteoporosis by quantifying bone mineral content and bone mineral density using dual-energy X-ray absorptiometry. Additionally, the hepatorenal toxicity of Radix Dipsaci contaminated with aflatoxin B1 was evaluated using hematoxylin-eosin staining and enzyme-linked immunosorbent assay (ELISA). Results The results indicated that aflatoxin B1 (AFB1) was the most frequently detected mycotoxin, found in 37.7% of the Radix Dipsaci samples. AFB1 contamination significantly altered the secondary metabolites of Radix Dipsaci . Specifically, there was a notable decrease in the levels of total saponins and akebia saponin D in the AFB1-contaminated samples, which exhibited a negative correlation with the levels of AFB1 contamination. However, the administration of a water decoction from AFB1-contaminated Radix Dipsaci did not result in significant improvements in bone mineral density, bone mineral salt content, the trabecular number, trabecular area, proportion of trabecular bone volume/tissue volume and trabecular separation in an osteoporosis mouse model. Additionally, we observed that approximately 16.04% of AFB1 could migrate from the raw herbs into the decoction, leading to hepatocyte and kidney cell damage, as well as increased levels of the oxidative stress molecule malondialdehyde and pro-inflammatory cytokines in the liver and kidney tissues of the osteoporosis model mice. Conclusion In summary, Radix Dipsaci is highly susceptible to mycotoxin contamination, particularly aflatoxin B1. The contamination of Radix Dipsaci with AFB1 not only impacts their saponin content and anti-osteoporosis effect but also induces hepatotoxicity and nephrotoxicity.
研究领域:
药理学
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毒理学
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民族药理学
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植物化学
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药物化学
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动物模型
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DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2021
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IF 2.63
Songsong Wang,Xiao Xiao,Ao Li,Peng Li
An-Gong-Niu-Huang Wan (AGNH) has been a well-known cinnabar- and realgar-containing compound recipe for cerebral diseases. Unfortunately, its clinical practice is often restrained by the specific hepatorenal toxicity of cinnabar and realgar (C + R). In previous research studies, we have found that the antioxidative and anti-inflammatory effects of its herbal constituents could mitigate the risks from the toxicity. The underlying detoxification mechanisms are still unsolved. The present study investigated the protective effects of AGNH’s herbal constituents on hepatorenal injury induced by C + R. For the mice treated with C + R, the increased expression levels of sensitive biomarkers of metal exposure and hepatorenal toxicity, including metallothionein (MT) in both hepatorenal tissues and kidney induced molecule-1 (KIM-1) in the kidney, were simultaneously reduced when C + R coadministered with other herbal medicines. In addition, the contents of trivalent As (AsIII), pentavalent As (Asv), and mercury (Hg) in hepatorenal tissues of mice were also significantly reduced benefiting from the herbal constituents in AGNH. Further mechanism studies showed that the herbal constituents in AGNH could downregulate the expressions of uptake transporters (AQP9 and OAT1) and upregulate the expressions of efflux transporters (P-gp, MRP2, and MRP4) in mice intoxicated by C + R. Our results suggested that AGNH’s herbal constituents protect the body against C + R-induced hepatorenal toxicity and accumulations of Hg and As, which could be associated with the reestablishment of heavy metal homeostasis and the detoxification system.
研究领域:
药理学
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毒理学
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分子生物学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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