Journal of Oceanology and Limnology
·
2024
·Vol. 42
·期 1
·163-173
·
IF 1.3
Ma Dandan,Zhou Qingli,Sui Liying,Guo Qingbin,Liu Huanhuan,Liang Honghe,Li Zhenjing,Sang Zhongna
Deltamethrin (DEL), a commonly used pyrethroid pesticide, results in higher reactive oxygen species (ROS) levels in aquatic animals, which consequently unbalance the redox state. Phlorizin (PHL) is a flavonoid and a natural product promising to prevent or reduce pesticide-induced oxidative stress. Artemia is a micro-crustacean widely used in marine hatcheries and an experimental aquatic organism for environmental toxicology research. This research aimed to evaluate the toxicity of DEL on Artemia and the antioxidative effect of PHL against the toxicity. Results show that 0.08-mg/mL PHL exerted its antioxidative effects on hatching percentage of the cysts in 24-h incubation and on body length and survival rate of Artemia in 12-d culture. After 12-d culture, 12-, 24-, and 36-h DEL exposure showed significant drops in SOD, CAT, and GSH-Px enzyme activities, and significant increases in ROS and malondialdehyde (MDA) levels in Artemia ( P <0.05). On the contrary, 0.08-mg/mL PHL application improved the enzyme activities and decreased the ROS and MDA levels ( P <0.05). Moreover, 0.08-mg/mL PHL significantly increased mRNA expression levels of Cu/Zn SOD, CAT, GST, HO-1, NQO1 , and Nrf2 , and decreased mRNA expression level of Keap1 in the DEL-exposed Artemia ( P <0.05). Therefore, DEL is toxic to Artemia , while PHL alleviates DEL-induced oxidative damage by possibly regulating the Nrf2 signaling pathway. This study provided a theoretical basis for PHL to reduce pesticide-induced toxicity in aquatic animals.
研究领域:
环境毒理学
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水产动物健康
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抗氧化研究
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DOI
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
·
2025
·
IF 3.3
Xiaoyu Wu,Chuanbo Ding,Xinglong Liu,Qiteng Ding,Shuai Zhang,Yue Wang,Ting Zhao,Wencong Liu
Carotid atherosclerosis (CAS) is a complex cardiovascular disease linked to inflammatory response and oxidative stress. This study aimed to develop and assess the therapeutic efficacy of Phlorizin liposomes (Phlorizin-Lips) in repairing CAS in rats. Phlorizin-Lips were prepared using the film dispersion method and evaluated for controlled release, antioxidant properties, and biocompatibility. The methodology included preparing Phlorizin-Lips, conducting in vitro and in vivo experiments, observing histopathological changes in carotid arteries in a rat model, and detecting inflammatory markers and antioxidant gene expression in arterial endothelial cells using immunoblotting and ELISA. Results showed that Phlorizin-Lips significantly lowered inflammatory markers TNF-α and IL-1β in endothelial cells while upregulating Nrf2 and its downstream antioxidant genes, enhancing the cells' antioxidant capacity and reducing oxidative damage by activating the Nrf2 signaling pathway. Additionally, Phlorizin-Lips reduced carotid plaque formation, improved vascular endothelial function, and promoted CAS repair. This study underscores Phlorizin's potential as a therapeutic agent for CAS and highlights the Nrf2 pathway's role in regulating inflammation and oxidative stress. Future research will explore the clinical potential of Phlorizin-Lips.
研究领域:
药理学
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心血管病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Toxicology Research
·
2022
·Vol. 11
·期 5
·863-871
·
IF 2.68
Xia Ling-Zi,Jiang Ming-Zhe,Liu Li-Lan,Wu Yi,Zhang Yi-Lin,Yang Li-Xia,Shen Xin-Yue,Zhang Qiu-Yu,Lin Min,Gao Hai-Tao
Humans are increasingly exposed to ubiquitous phthalates (PEs), e.g. butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), and di(2-ethylhexyl) phthalate (DEHP), which are widely used plasticizers in polymer products. This study was aimed to investigate the effect of phytochemical quercetin (Que) on hepatotoxicity caused by the mixture of the 3 commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty male Sprague–Dawley rats were randomly divided into control group, MPEs group, and MPEs combined Que at Low-, Median-, and High-dose groups; rats in MPEs group were orally administered with 900 mg/kg/d MPEs, whereas rats in MPEs combined Que groups were simultaneously treated with 900 mg/kg/d MPEs and respectively 10, 30, and 90 mg/kg/d Que. The intervention last 30 days. Compared with control group, serum ALT, AST, LDH and AKP, and hepatic MDA, SOD, CAT and GPx were significantly increased, whereas, serum albumin and total protein were significantly decreased in MPEs group (P < 0.05); hepatic histopathological observation showed numerous inflammatory cells infiltration, hepatocyte ballooning degeneration, and numerous residual erythrocytes in the central vein in MPEs group. Western-blot analysis showed that hepatic Keap1 was downregulated, whereas Nrf2 and HO-1 were upregulated in MPEs group (P < 0.05). However, the alterations of these parameters were alleviated in MPEs combined Que at Median- and High-dose groups. The results indicated that MPEs-induced hepatic oxidative stress, and caused hepatic injuries; whereas, Que inhibited MPEs’ hepatotoxicity, which might relate to Que’s ability of quenching free radicals directly, and restored the regulation of Nrf2 signaling pathway.
研究领域:
毒理学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Fang Wang,Ke Wang,BaoRu Fang,SiQi Geng,Ying Li,HuiFeng Qian,YiNuo Lin,ZhangSen Yu
Doxorubicin-induced cardiomyopathy (DIC) is a toxic side effect that cannot be ignored during chemotherapy for malignant tumors. In this work, we synthesized a novel nano-chemotherapeutic drug based on Prussian blue nanozyme to alleviate DIC. Hollow mesoporous Prussian blue (HmPB) nanoparticles were used as a carrier to load doxorubicin (DOX) through electrostatic adsorption and obtain a novel chemotherapy drug, HmPB(DOX). I n vivo and in vitro chemotherapy efficacy and acute toxicity evaluation experiments were conducted. The results suggest that HmPB(DOX) exhibits pH-responsive characteristics and minimizes the release of DOX from within HmPB(DOX) in cardiomyocytes. However, in the acidic tumor microenvironment, the release of DOX from HmPB(DOX) is notably enhanced. More importantly, HmPB(DOX) possesses excellent antioxidant enzyme activity, effectively clearing DOX-induced reactive oxygen species (ROS) and alleviating oxidative stress in cardiomyocytes. Doxorubicin is pivotal in the chemotherapy of malignant tumors. This study presents novel insights for mitigating the toxic and side effects of DOX, offering new strategies to enhance tolerance to chemotherapy.
研究领域:
药理学
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纳米医学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2024
·
IF 3.8
Jiamei Zhu,Xueyan Dai,Yan Wang,Ting Cui,Bingyan Huang,Dianyun Wang,Wenjing Pu,Caiying Zhang
Cadmium ( Cd ) and high molybdenum ( Mo ) are injurious to the body. Previous research has substantiated that Cd and Mo exposure caused testicular injury of ducks, but concrete mechanism is not fully clarified. To further survey the toxicity of co-exposure to Cd and Mo in testis, 40 healthy 8-day-old Shaoxing ducks ( Anas platyrhyncha ) were stochasticly distributed to four groups and raised with basic diet embracing Cd (4 mg/kg Cd) or Mo (100 mg/kg Mo) or both. At the 16th week, testis tissues were gathered. The characteristic ultrastructural changes related to apoptosis and ferroptosis were observed in Mo or Cd or both groups. Besides, Mo or Cd or both repressed nuclear factor erythroid 2-related factor 2( Nrf2 ) pathway via decreasing Nrf2, Heme oxygenase-1 ( HO-1 ), NAD(P)H quinone oxidoreductase 1 ( NQO1 ), Glutamate-cysteine ligase catalytic subunit ( GCLC ) and Glutamate-cysteine ligase modifier subunit ( GCLM ) mRNA expression of and Nrf2 protein expression, then stimulated apoptosis by elevating Bcl-2 antagonist/killer-1 ( Bak-1 ), Bcl-2-associated X-protein ( Bax ), Cytochrome complex ( Cyt-C ), caspase-3 mRNA expression, cleaved-caspase-3 protein expression and apoptosis rate, as well as reducing B-cell lymphoma-2 ( Bcl-2 ) mRNA expression and ratio of Bcl-2 to Bax, and triggered ferroptosis by upregulating Acyl-CoA Synthetase Long Chain Family Member 4 ( ACSL4 ), transferrin receptor ( TFR1 ) and Prostaglandin-Endoperoxide Synthase 2 ( PTGS2 ) expression levels, and downregulating ferritin heavy chain 1 ( FTH1 ), ferritin light chain 1 ( FTL1 ), ferroportin 1 ( FPN1 ), solute carrier family 7 member 11 ( SCL7A11 ) and glutathione peroxidase 4 ( GPX4 ) expression levels. The most obvious changes of these indexes were observed in co-treated group. Altogether, the results announced that Mo or Cd or both evoked apoptosis and ferroptosis by inhibiting Nrf2 pathway in the testis of ducks, and co-exposure to Mo and Cd exacerbated these variations.
研究领域:
毒理学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Animal Diseases
·
2024
·Vol. 4
·期 1
·1-16
·
IF 0
Liu Jinglei,Zhang Yuhan,Song Mengzhen,Guo Xuming,Fan Jinping,Tao Shiyu
Oxidative stress is an important contributor to gastrointestinal diseases in multiple ways. Taurodeoxycholic acid (TDCA) is a metabolite of bile acids and has anti-inflammatory and protective effects on the intestinal tract. However, whether TDCA can alleviate oxidative stress in the intestine is still unclear. Here, we investigated the effects of TDCA on diquat-induced oxidative stress in the jejunum and its mechanism. The results revealed that TDCA increased the concentrations of antioxidant enzymes in the serum, jejunal tissue and intestinal epithelial cells of the mice, as did the expression of tight junction-associated proteins and the Nrf2 protein in the jejunal epithelial tissue and intestinal epithelial cells. We then explored the mechanism of Nrf2 with ML385 (a specific Nrf2 inhibitor). The results showed that after ML385 treatment, the levels of antioxidant enzymes were significantly decreased in the serum, jejunum, and intestinal epithelial tissues of the mice. The expression of tight junction proteins in jejunum epithelial tissues and intestinal epithelial cells was also decreased. In conclusion, our study suggests that TDCA alleviates oxidative stress to improve intestinal barrier function through the Nrf2-mediated signaling pathway. These findings help elucidate the role of TDCA in protecting the intestinal barrier and its mechanism of action, providing insights for the prevention and treatment of intestinal diseases caused by oxidative stress.
研究领域:
生物化学
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分子生物学
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药理学
✓ 已验证
DOI
Advanced Science
·
2025
·
IF 14.1
Runyu Dong,Yao Fei,Yiren He,Peng Gao,Bo Zhang,Menglin Zhu,Zhixiong Wang,Longfei Wu,Shuai Wu,Xiaoming Wang,Juan Cai,Zhiqiang Chen,Xueliang Zuo
Drug resistance remains a major hurdle for the therapeutic efficacy of lenvatinib in hepatocellular carcinoma (HCC). However, the underlying mechanisms remain largely undetermined. Unbiased proteomic screening is performed to identify the potential regulators of lenvatinib resistance in HCC. Patient-derived organoids, patient-derived xenograft mouse models, and DEN/CCl 4 induced HCC models are constructed to evaluate the effects of HECTD2 both in vitro and in vivo. HECTD2 is found to be highly expressed in lenvatinib-resistant HCC cell lines, patient tissues, and patient-derived organoids and xenografts. In vitro and in vivo experiments demonstrated that overexpression of HECTD2 limits the response of HCC to lenvatinib treatment. Mechanistically, HECTD2 functions as an E3 ubiquitin ligase of KEAP1, which contributes to the degradation of KEAP1 protein. Subsequently, the KEAP1/NRF2 signaling pathway initiates the antioxidative response of HCC cells. Lactylation of histone 3 on lysine residue 18 facilitates the transcription of HECTD2. Notably, a PLGA-PEG nanoparticle-based drug delivery system is synthesized, effectively targeting HECTD2 in vivo. The NPs achieved tumor-targeting, controlled-release, and biocompatibility, making them a promising therapeutic strategy for mitigating lenvatinib resistance. This study identifies HECTD2 as a nanotherapeutic target for overcoming lenvatinib resistance, providing a theoretical basis and translational application for HCC treatment.
研究领域:
肿瘤学
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分子生物学
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药物研发
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Pharmacology Research & Perspectives
·
2025
·Vol. 13
·期 3
·e70094
·
IF 2.3
Lei Zhu,Mengru Ding,Lina Liu,Pingchuan Yuan,Taili Shao,Chunyan Liu,Chuanhu Xi,Jun Han,Yuyan Zhou,Donglin Zhang,Guodong Wang
Diabetic nephropathy (DN) is a common complication of diabetes mellitus, with oxidative stress playing a critical role in its development. Burdock fructooligosaccharide (BFO), a major compound in Burdock, exhibits antioxidative effects. However, its mechanisms of action and effects on diabetic nephropathy are not clear enough. This study aims to explore the mechanisms of BFO and its impact on streptozotocin-induced diabetic nephropathy in mice. Male C57BL/6J mice were randomly divided into normal control, DN, and BFO groups. Relevant serum biochemical parameters were detected using kits. Renal injury was evaluated through fluorescence microscopy, histopathology, and transmission electron microscopy. Nrf2/HO-1 signaling was analyzed via quantitative real-time PCR, western blotting, and immunohistochemistry. In DN mice, BFO significantly reduced fasting blood glucose, kidney index, urine protein, serum creatinine, blood urea nitrogen, total cholesterol, triglyceride, and low-density lipoprotein cholesterol, while significantly increasing high-density lipoprotein, SOD, and CAT levels. Additionally, BFO protected against streptozotocin-induced renal injury, restored podocyte function, increased both mRNA and protein expression of Nrf2, HO-1, and Bcl-2, and decreased those of Bax. In conclusion, BFO can be used to treat streptozotocin-induced renal injury in mice and is a promising candidate for diabetic nephropathy treatment.
研究领域:
药理学
·
分子生物学
·
糖尿病研究
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2021
·
IF 4.432
Xin Guo,Pingping Cao,Xiongfeng Lian,Meng Hu,Jingyi Zhao,Wenjing Shen,Haili Wang,Hailong Yu,Yingzhu Chen
Phillyrin, a natural plant extract, has significant antioxidant and anti-apoptotic effects. However, its effect on intracerebral hemorrhage (ICH) remains unclear. In this study, we investigated a potential role for phillyrin in the regulation of the oxidative stress and apoptosis induced by ICH. A model of ICH was induced by collagenase IV (0.2 U in 1 μl sterile normal saline) in male C57BL/6J (B6) mice and different doses of phillyrin (5, 15, or 30 mg/kg) were intraperitoneally (i.p.) injected at 30 min, 6 h, and 22 h after modeling. We found that phillyrin significantly reduced neural function and lesion volume, improved injury of white and grey matter around the lesion, decreased apoptosis and oxidative stress, increased the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase 1(HO-1), NADPH quinone oxidoreductase 1 (NQO1) and Superoxide Dismutase-1(SOD-1) in vitro and in vivo , and protected neurons from the stimulation of hemin by promoting Nrf2 nuclear translocation. Treatment with ML385 (Nrf2 inhibitor) completely reversed the protective effects of phillyrin in vivo after ICH injury. Based on our findings, we conclude that phillyrin treatment alleviates ICH injury-induced apoptosis and oxidative stress via activation of the Nrf2 signaling pathway, highlighting a potential role for phillyrin as an ICH therapeutic.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2019
·
IF 5.515
Peng Chen,Fuchao Chen,Ben-hong Zhou
Aging is a complex physiological phenomenon associated with oxidative stress damage. The objective of this study was to investigate the potential effects of leonurine on D-galactose-induced aging in mice and its possible mechanisms. In this study, we first tested the antioxidant activity of leonurine in vitro . A subcutaneous injection of D-galactose in mice for 8 weeks was used to establish the aging model to evaluate the protective effects of leonurine. The results showed that treatment with 150 mg·kg -1 leonurine could improve the mental condition, organic index, and behavioural impairment; significantly increase the activities of antioxidative enzymes including SOD, CAT, and T-AOC; and ameliorate the advanced glycation end product (AGE) level and histopathological injury. Furthermore, the Western blotting data revealed that leonurine supplementation noticeably modulated the suppression of the Nrf2 pathway and upregulated the downstream expression of HO-1 and NOQ1 in aging mice. Additionally, leonurine treatment activated Nrf2 nuclear translocation in both aging mice and normal young mice, and the expression levels of Nrf2 in normal young mice was higher than those in naturally aging mice. In conclusion, our findings suggest that leonurine is a promising agent for attenuating the aging process, and the underlying molecular mechanisms depend on activating the Nrf2 pathway.
研究领域:
老年学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2019
·
IF 4.527
Hongyan Yu,Jian Zhang,Qiang Ji,Kaiyuan Yu,Peiyan Wang,Miao Song,Zheng Cao,Xueyan Zhang,Yanfei Li
The present study aimed to investigate whether melatonin (MT) treatment can attenuate immunotoxicity induced by aluminum chloride (AlCl 3 ) in rat spleen. Forty-eight healthy male Wistar rats were randomly allocated and treated with AlCl 3 and/or MT. Rats were orally administered with AlCl 3 for 90 days, from 61st days, rats were injected intraperitoneally with MT for 30 days. Firstly, we found that MT relieved the AlCl 3 -induced immunosuppression by improving spleen structural damage, CD3 + and CD4 + T lymphocyte subsets, IL-2 and TNF-α mRNA expressions and decreasing CD8 + T lymphocyte subsets. Secondly, MT attenuated the AlCl 3 -induced oxidative stress in rat spleen by decreasing the levels of ROS and MDA , while increasing the activities of SOD and CAT. Thirdly, MT relieved the AlCl 3 -induced apoptosis in rat spleen by increasing the MMP and Bcl-2 mRNA and protein expressions, while decreasing apoptosis rates, activity of Caspase-3 and pro-apoptotic gene expression. Finally, MT increased Nrf2 nuclear translocation, and Nrf2 target genes (HO-1, NQO1, SOD1 and CAT) mRNA expressions in the spleen of AlCl 3 -exposed rat. These results suggest that MT may alleviate AlCl 3 -induced immunotoxicity by inhibiting oxidative stress and apoptosis associated with the activation of Nrf2 signaling pathway, which could lay the foundation for the treatment of AlCl 3 immunotoxicity.
研究领域:
药理学
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免疫学
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2021
·
IF 1.571
Fang Chen,Shi-Yun Huang,Shu-Qing Xiang,Xiao-Xu Qiao,Guo-Chao Liao,Zhong-Qiu Liu,Hua Zhou,Peng Wu
Two new phenolic glycosides (1-2), along with six existing compounds (3-8), were isolated from the ethanolic extract of Ilex pubescens roots, a traditional folk medicine. These structures were determined using HR-ESI-MS, IR, UV, and NMR (including 1 D, 2 D-NMR). The anti-inflammatory activities of three phenolic glycosides (1-3) were evaluated in the human HepG2 cell lines. The results showed that compound 3 could induce P-gp and BCRP expression through the Nrf2-mediated pathway.
研究领域:
天然产物化学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）