TOXICOLOGY
·
2023
·
IF 4.5
Xinyu Wu,Yeyun Ma,Xueqing Li,Nana He,Tianmeng Zhang,Feixue Liu,Huimiao Feng,Jingquan Dong
Indiscriminate use of pesticides not only leads to environmental pollution problems, but also causes poisoning of non-target organisms. Abamectin (ABM), a widely used insecticide worldwide, is of wide concern due to its persistence in the environment and its high toxicity to fish. The kidney, as a key organ for detoxification, is more susceptible to the effects of ABM. Unfortunately, few studies investigated the mechanisms behind this connection. In this study, carp was used as an indicator organism for toxicological studies to investigate renal damage caused by ABM residues in carp. In this work, carp were exposed to ABM (0, 3.005, and 12.02 μg/L) for 4 d and the nephrotoxicity was assessed. Histopathological findings revealed that ABM exposure induced kidney damage in carp, as well as an increase Creatinine and BUN levels. Meanwhile, ABM as a reactive oxygen species (ROS) stimulator, boosted ROS bursts and lowered antioxidant enzyme activity while activating the body's antioxidant system, the Nrf2-Keap1 signaling pathway. The accumulation of ROS can also lead to the imbalance of the body's oxidation system, leading to oxidative stress. At the same time, NF-κB signaling pathway associated with inflammation was activated, which regulated expression levels of inflammatory cytokines ( TNF-α , IL-6 , IL-1β , and iNOS increased, while IL-10 and TGF-β1 decreased). In addition, ABM exposure caused structural damage to kidney mitochondria of carp, resulting in decreased mitochondrial membrane potential and ATP production capacity, and mediated apoptosis through endogenous pathways Bax/Bcl-2/Caspase-9/Caspase-3. In conclusion, ABM caused kidney damage in carp by inducing oxidative stress, inflammation, and apoptosis through mitochondrial pathway. These findings will be useful for future research into molecular mechanisms of ABM-induced nephrotoxicity in aquatic organisms.
研究领域:
毒理学
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环境科学
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水生生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Wei-yu Guo,Ding-yan Lu,Zhi-zhong Guan,Lin Zheng,Shuai-shuai Chen,Ting Liu
To investigate the impact of the ethanoic fractions of Periploca forrestii Schltr. (P. forrestii) in ameliorating the liver injury caused by fluoride ingestion and to explore the potential mechanisms. Initially, an in vitro fluorosis cell model was constructed using the human normal liver cell line (L-02) induced by fluoride. Cell viability was assessed using the CCK-8 assay kit. The lactate dehydrogenase (LDH) assay kit was utilized to measure LDH content in the cell supernatant, while the malonic dialdehyde (MDA) assay kit was employed to determine MDA levels within the cells. Subsequently, a fluorosis rat model was established, and LDH content in the cell supernatant was measured using the LDH assay kit. Various parameters, including MDA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and reactive oxygen species (ROS) content within the cells, were detected using appropriate assay kits. Additionally, cell apoptosis rate was determined using the Annexin V-FITC/PI cell apoptosis assay kit. The protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Cleaved Caspase-3, Caspase-9, and Cleaved Caspase-9 were analyzed through Western blotting. Compared to the model group, the ethanolic fraction D of P.forrestii (Fr.D) increased cell viability ( P < 0.01) and decreased LDH and MDA levels ( P < 0.01). In the high-dose Fr.D treatment group of fluoride-poisoned rats, serum ALT, AST, LDH and MDA levels significantly decreased ( P < 0.01). Results from rat primary cells exhibited that the Fr.D administration group exhibited significantly higher cell survival rates than the fluoride group ( P < 0.01). Similarly, primary rat cells treated with Fr.D showed enhanced cell viability ( P < 0.05) and reduced apoptosis rate, LDH, MDA, SOD, GSH-Px, CAT, and ROS levels ( P < 0.05) compared to the model group. Western blot analysis indicated that the Fr.D treatment group elevated the Bcl-2/Bax protein expression ratio and reduced Caspase-3 and Caspase-9 activation levels ( P < 0.01) compared to the model group. The results suggest that components within the Fr.D from Periploca forrestii may alleviate fluoride-induced liver injury by potentially counteracting oxidative stress and cell apoptosis.
研究领域:
药理学
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毒理学
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细胞生物学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2018
·
IF 7.877
Chenfeng Xu,Yu Sun,Yan Qi,Yulin Yu,Yangzhou He,Mei Hu,Qian Hu,Tingting Wu,Dan Zhang,Lihuan Shang,Huan Deng,Zhiping Zhang
Tumor heterogeneity is considered as one of main obstacles to limit the clinical application of stimuli-responsive nanocarriers . Multidrug resistance (MDR) is also a major challenge in cancer chemotherapy . Here, we developed a tumor redox heterogeneity-responsive prodrug with self-induced reactive oxygen species (ROS) amplification property for facilitating rapid drug release and overcoming MDR and lung metastasis . The prodrug can self-assemble into polymer micelles (PMs) with high drug loading content (~30%), good physiological stability, prolonged systemic circulation and enhanced tumor distribution. Moreover, the prodrug PMs can stimulate tumor-specific ROS signal amplification, which provided a replenishment of consumed ROS necessary for rapid and complete drug release. The elevated ROS could not only evoke the mitochondria-dependent apoptosis by caspase-9/3 activation, but also inhibit inherent and acquired drug resistance by altering expression of Bcl-2 protein family and by reducing mitochondria membrane potential (ΔΨm) and ATP level in cancer cells. As a result, the prodrug PMs showed enhanced efficacy for inhibiting tumor growth in S180 sarcoma tumor model and in drug-resistant tumor model MCF-7/ADR and preventing lung metastasis in 4T1 in situ breast cancer model. This novel approach reported here may provide a promising strategy in the design of stimuli-responsive nanocarriers for efficient therapy of multidrug resistant and metastatic tumor.
研究领域:
癌症治疗
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药学
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纳米技术
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Zhiyuan Li,Liu Zhang,Quanshun Li
Herein, N -acetyl- l -leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine 2000 . Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential as biocompatible carriers for realizing effective tumor gene therapy.
研究领域:
癌症生物学
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分子生物学
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基因治疗
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 46
·期 3
·1295-1307
·
IF 3.591
Zhi-Gang Yin,Xiong-Wei Liu,Hui-Juan Wang,Min Zhang,Xiong-Li Liu,Ying Zhou
A highly efficient synthesis of structurally diverse ortho-acylphenol–diindolylmethane hybrids 3 using carboxylic acid-activated chromones as versatile synthetic building blocks is reported here for the first time, through 1,4-nucleophilic addition and followed by a decarboxylation and pyrone ring opening reaction process. The newly synthesized compounds were evaluated for their in vitro anticancer activity, and most of the compounds displayed good anticancer activities against four tested tumor cells (A549, PC-3, NCI-H1299, Caco-2). Among these compounds, compound 3t displayed the most potent and broad-spectrum anti-proliferative inhibition against the tested cell lines, especially A549 cells, and was more potent than arundine and cisplatin drugs, and had selectivity in cancer cells compared to MRC-5 and HK-2 normal cells. Preliminary mechanism studies showed that compound 3t exerted an anti-tumor effect in A549 cells by inhibiting the proliferation, colony formation and migration of A549 cells, and inducing cycle arrest at the G0/G1 phase and apoptosis. Furthermore, treatment of A549 cells with compound 3t caused increased ROS content and induced MMP collapse; western blot analysis showed that the expression level of p53 was significantly increased; Bax/Bcl-2 ratio and Cyt c were increased, and caspase-9, -3, and PARP were cleaved. These studies showed that compound 3t could induce apoptosis of A549 cells through the mitochondrial pathway, which was related to the activation of p53 and the generation of ROS. Thus, our results indicate that compound 3t may be used as a promising skeleton for the development of new anti-tumour drugs.
研究领域:
药物化学
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肿瘤学
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药学
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细胞生物学
✓ 已验证
DOI
高影响因子
Environmental Science-Nano
·
2023
·Vol. 10
·期 12
·3389-3400
·
IF 7.3
Shuoli Ma,Wen-Xiong Wang
Marine hydrosphere is in grave danger if extreme weather conditions, such as high temperatures and heat waves, become the norm. The functional characteristics of nano Zn oxides (nZnO) might provide a “booster substance” that helps marine species to endure environmental stress. In the present study, physiological indicators and simulated severe environments were used to evaluate the antioxidative ability of nZnO in marine rabbitfish Siganus fuscescens, with an aim to help them resist extreme environmental stress. Rabbitfish were exposed to different diets with ZnSO4 and nZnO at the optimum requirement level (Zn content of 62.5 μg g−1), and then challenged with a low dissolved oxygen concentration and higher temperature. We demonstrated that dietary nZnO promoted the anti-oxidation defense system of the rabbitfish by improving the activities of the antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio without tissue damage. Compound stressors reduced the median survival duration of the rabbitfish from 4.25 h to 2.5 h (dietary exposure) and 9 h to 5.75 h (dietary nZnO exposure) compared to single environmental stress. nZnO downregulated the HIF gene expression and increased the prolyl hydroxylase (PHD) activity in the liver of the rabbitfish. After 10 h of extreme environmental exposure, the gene expression results indicated that nZnO inhibited the NF-κB/IL-1β/IL-6 pathway and TNF-α/Bcl-2/Bax/caspase 9 pathway and activated the akt/mTOR/elovl5 and elovl8 pathway of the rabbitfish to maintain the resilience of the fish under the extreme environment. These results strongly suggested that nZnO may improve the anti-oxidation ability of fish to resist extreme environments.
研究领域:
海洋生物学
·
环境科学
·
水产养殖
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）