FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Huanyan Wu,Linlin Qu,Xue Bai,Chenhui Zhu,Yuan Liu,Zhiguang Duan,Hongyan Liu,Rongzhan Fu,Daidi Fan
Hepatocellular carcinoma (HCC) is the third most lethal cancer in the world. Recent studies have shown that suppression of autophagy plays an important role in the development of HCC. Ginsenoside Rk1 is a protopanaxadiol saponin isolated from ginseng and has a significant anti-tumor effect, but its role and mechanism in HCC are still unclear. In this study, a mouse liver cancer model induced by diethylnitrosamine and carbon tetrachloride (DEN + CCl 4 ) was employed to investigate the inhibitory effect of Rk1 on HCC. The results demonstrate that ginsenoside Rk1 effectively inhibits liver injury, liver fibrosis, and cirrhosis during HCC progression. Transcriptome data analysis of mouse liver tissue reveals that ginsenoside Rk1 significantly regulates the AMPK/mTOR signaling pathway, autophagy pathway, and apoptosis pathway. Subsequent studies show that ginsenoside Rk1 induces AMPK protein activation, upregulates the expression of autophagy marker LC3-II protein to promote autophagy, and then downregulates the expression of Bcl2 protein to trigger a caspase cascade reaction, activating AMPK/mTOR-induced toxic autophagy to promote cells death. Importantly, co-treatment of ginsenoside Rk1 with autophagy inhibitors can inhibit apoptosis of HCC cells, once again demonstrating the ability of ginsenoside Rk1 to promote autophagy-dependent apoptosis. In conclusion, our study demonstrates that ginsenoside Rk1 inhibits the development of primary HCC by activating toxic autophagy to promote apoptosis through the AMPK/mTOR pathway. These findings confirm that ginsenoside Rk1 is a promising new strategy for the treatment of HCC.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Ming-hui Jin,Jun-nan Hu,Ming Zhang,Zhaojie Meng,Guo-ping Shi,Zi Wang,Wei Li
The production and application of nanoplastics has been increased during decades, and the enterotoxicity caused by their bioaccumulation has attracted vast attention. Maltol was proved to exert a protective effect on gut damage induced by carbon tetrachloride and cisplatin, indicating its confrontation with nanoplastics-induced intestinal toxicity. To explore the ameliorative effects of maltol on polystyrene nanoplastics (PS)-mediated enterotoxicity and the underlying mechanism, the mice were exposed to PS (100 mg/kg), combining with or without the treatment of maltol treatment at 50 and 100 mg/kg. We found PS exposure caused intestinal barrier damage and enterocyte apoptosis, while lysosomal dysfunction and autophagic substrate degradation arrest in enterocytes of mice were also observed. In addition, PS exacerbated the disturbance of the intestinal microbial community , affected the abundance of lysosome and apoptosis-related bacterial genes, and decreased the number of known short-chain fatty acid (SCFA) producing bacteria. However, those alterations were improved by the maltol treatment. Maltol also protected the human intestinal Caco-2 cells from PS-induce damages. Mechanistic studies showed maltol promoted TFEB nuclear translocation through the AMPK/mTOR signaling pathway to restore lysosomal function and reduce autophagy dependent apoptosis. The findings in the present work might help to elucidate the potential molecular mechanisms of PS-induced enterotoxicity. For the first time to our knowledge, the protective effect of maltol on PS-induced intestinal injury was studied from multiple perspectives, which provided a potential therapeutic approach for diseases caused by environmental pollution .
研究领域:
毒理学
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胃肠病学
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环境科学
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细胞生物学
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微生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
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IF 5.4
Yudi Yao,Yang Chen,Huijian Chen,Xin Pan,Xiaojun Li,Wenqi Liu,Yerlan Bahetjan,Binan Lu,Kejian Pang,Xinzhou Yang,Zongran Pang
Ethnopharmacological relevance Black mulberry ( Morus nigra L.) is an ancient dual-use plant resource for medicine and food. It is widely used in Uyghur folklore for hypoglycemic treatment and is a folkloric plant medicine with regional characteristics. However, the mechanism of Morus nigra L. treatment in diabetes mellitus has not been fully understood, especially from the perspective of hepatic lipid accumulation is less reported. Objective of this study This study was to explore the potential of Morus nigra L. fruit ethyl acetate extract (MNF-EA) to reduce blood sugar levels by preventing the production of hepatic lipogenesis and to provide more evidence for the use of MNF-EA as an adjuvant therapy for type 2 diabetes mellitus (T2DM). Materials and methods In this study, the chemical composition of MNF-EA was first analyzed and characterized using UPLC-Q-TOF-MS technique. A series of in vitro studies were performed with HepG2-IR cells and oleic acid (OA)-induced HepG2 cells, including MTT assay, glucose uptake assay, oil red O staining and Western blot analysis . The STZ-HFD co-induced T2DM mice were employed for in vivo research, including physical indices, biochemical analysis, histopathological examination, and Western blot analysis. Results The 19 compounds in MNF-EA were identified by UPLC-Q-TOF-MS technique. Insulin resistance (IR) and lipid droplet accumulation in HepG2 cells were greatly improved by MNF-EA treatment, which had no appreciable side effects at the dosage used. In T2DM mice, MNF-EA decreased fasting blood glucose (FBG), saved body weight, and significantly improved oral glucose tolerance (OGTT) and IR status. In addition, MNF-EA treatment also improved lipid metabolism disorders and liver function in T2DM mice. Histopathological sections showed that MNF-EA treatment reduced hepatic steatosis . Mechanistic studies suggest that MNF-EA acted through the AMPK/mTOR pathway. Conclusions These results suggest that MNF-EA has great potential to reverse the metabolic abnormalities associated with T2DM by regulating the AMPK/mTOR signaling pathway. Therefore, we believe that MNF is a promising medicinal and food-homologous agent to improve T2DM.
研究领域:
药理学
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民族药理学
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糖尿病研究
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代谢紊乱
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植物化学
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细胞生物学
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动物模型
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产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2020
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IF 3.343
Gang Wang,Yang Yu,Yu-Zhu Wang,Pei-Hao Yin,Ke Xu,Heng Zhang
In this study, isoliquiritigenin (ISL) incorporated nanoliposomes were prepared and their effects on colorectal cancer (CRC) cell lines were investigated. Herein, we sought to explore the anti-cancer mechanisms of ISL loaded nanoliposomes (ISL-NLs) on AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathways mediated glycolysis. Also, the key targets such as caveolin 1 (CAV1), glucose transporters and Akt/mTOR that promote glycolysis, and are activated via the induction of α-enolase (ENO1), fructose bisphosphate aldolase A (ALDOA) and monocarboxylate transporter 4 (MCT4) expressions were also investigated. It was shown that ISL-NLs significantly suppressed the proliferation and glucose uptake of CRC cell by potentially regulating the glycolysis and lactate targets as well as pathways that formed the basis of the anti-CRC effects of ISL-NLs. The mechanism underlying this effect was further validated via the regulation of some key targets such as ENO1, ALDOA, lactate dehydrogenase A (LDHA) and MCT4 in glycolysis coupled with cellular myelocytomatosis oncogene (c-myc), hypoxia-inducible factor 1-alpha (HIF-1α) in protein kinase B/mTOR (Akt/mTOR) pathways. Moreover, the AMPK proteins were identified to be up-regulated while the lactic acid production was suppressed by ISL-NLs in the CRC cells, indicating that ISL-NLs had an inhibitory effect on AMPK mediated glycolysis and lactate production. Altogether, these results have provided insights into the mechanism underlying the key role that liposomal ISL played in the multiple inhibition of AMPK and Akt/mTOR mediated glycolysis and lactate generation, which may be regulated as the alternative metabolic pathways of CRC as well as serve as adjuvant therapy for the disease.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENT INTERNATIONAL
·
2020
·
IF 7.577
Miaoling Lin,Rui Hua,Jing Ma,Yao Zhou,Pei Li,Xiya Xu,Zhiqiang Yu,Song Quan
Background Bisphenol A (BPA) is a widespread endocrine-disrupting chemical with estrogen like effects, which could interfere with the human reproductive system by disrupting the normal function of granulosa cells (GCs) leading to abnormal ovarian function. However, the mechanism of its toxicity on human GCs has not been clearly described thus far. Methods 106 normogonadotropic infertile women undergoing their first in-vitro fertilization-embryo transfer (IVF-ET) cycle were recruited. Urinary BPA level and the early outcomes of IVF-ET were analysed. Patients were divided to low and high BPA exposure groups using the median urinary BPA concentration as the cut-off value. In-vivo and in-vitro studies were conducted using mice and human granulosa cell line (KGN cells). Female Kunming mice approximately 6–8 weeks of age were poisoned with BPA at different dosages (1, 10 or 100 μg/kg) by oral gavage once daily for 2 weeks, while KGN cells were exposed to BPA at the concentration of 1, 10 or 100 nM for 24 h, 48 h or 72 h. BPA-induced ovarian morphologic changes were analysed by histopathology investigation. Cell viability and apoptosis were evaluated using CCK-8, TUNEL and flowcytometric, respectively. Hormone levels were determined using ELISA and the molecular mechanism studies were conducted using immunofluorescence, RT-PCR and western blots. Results The oocyte retrieval rate, maturation rate and embryo implantation rate significantly decreased with the higher level of urinary BPA concentration. Peak E2 level was lower in high BPA group, but no statistical significance could be observed. In BPA treated mice, cystic dilation of the follicles with a decreased number of GCs could be observed histopathologically. Decreased E2, P4 and AMH level and GCs autophagy could be detected both in-vivo and in-vitro with the activation of AMPK/mTOR/ULK1 signalling pathway. As being confirmed in KGN cells, phosphorylated AMPK and ULK1 increased while phosphorylated mTOR decreased, and by inhibition autophagy using knockdown of AMPK or 3-MA, adverse effects of BPA exposure in-vitro could be reversed. Conclusion BPA exposure might abnormally influence human ovarian functions leading to abnormal folliculogenesis by activation of autophagy in GCs through AMPK/mTOR/ULK1 pathway.
研究领域:
内分泌学
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生殖生物学
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毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
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IF 4.8
Luyao Liu,Ruikun Wang,Weijuan Gao,Xianming Hou,Xiaofei Jin,Yanmeng Zhao,Xiaohong Zhou,Yi Zhang
Ethnopharmacological relevance Cerebral ischemia-reperfusion (I/R) injury is a common complication of ischemic stroke, with autophagy and pyroptosis playing key roles. Huangqi and Danggui (HQDG) are a commonly used drug pair of Chinese traditional medicine for clinical treatment of ischemic stroke. Aim of the study The study aims to investigate the interaction between autophagy and pyroptosis regulated by HQDG through the AMPK/mTOR signaling pathway during cerebral I/R injury. Materials and methods Model of middle-cerebral artery occlusion/reperfusion (MCAO/R) in SD rats was established using the Longa suture method. The components of traditional Chinese medicine were detected by liquid chromatography coupled to quadrupole orbitrap high resolution mass spectrometry (LC/MS). Neurological deficits were evaluated by neurological function score. Changes of cerebral blood flow were detected by a laser speckle blood flow imaging instrument. The volume of cerebral infarction was observed by 2,3,5-Chlorotriphenyltetrazolium (TTC) staining. The permeability of the blood-brain barrier was measured by Evans blue test. Neurovascular unit and autophagosomes in brain tissue were assessed by transmission electron microscopy. Neuronal pyroptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL)/Caspase-1 staining. The expression of autophagy related proteins, pyroptosis related proteins, and AMPK/mTOR pathway related proteins were detected by Western blot. Results After cerebral I/R injury, autophagy and pyroptosis, were characterized by increased number of autophagosomes and pyroptosis cells, upregulated expression of Beclin 1, LC3-II/LC3-I, NLRP3, cleaved Caspase-1, IL-1beta, IL-18 proteins, and downregulated expression of P62 proteins. HQDG significantly improved neurological function, reduced the volume of cerebral infarction, increased cerebral blood flow, improved blood-brain barrier permeability and the function of neurovascular units. Autophagy was further activated and pyroptosis was significantly inhibited by HQDG, which promoted increased number of autophagosomes, enhanced expression of Beclin 1, LC3-II/LC3-I proteins, reduced expression of P62, NLRP3, cleaved Caspase-1, IL-1beta, and IL-18 proteins, and downregulated the number of pyroptosis cells. On the other hand, after administering 3-Methyladenine (3-MA) to inhibit autophagy, the above effects of HQDG were significantly inhibited. Besides, HQDG promoted AMPK phosphorylation, and weakened mTOR phosphorylation. However, after the administration of AMPK inhibitor Compound C, HQDG caused increase in Beclin 1 and LC3-II/LC3-I, reduced P62 and NLRP3, and cleaved Caspase-1 protein expression, whereas cerebral blood flow decreased. Conclusion HQDG alleviated pyroptosis by promoting autophagy via AMPK/mTOR signaling pathway after middle-cerebral artery occlusion/reperfusion in rats, showing its potential for treatment of cerebral I/R injury in humans.
研究领域:
药理学
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神经科学
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中医药
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR CARCINOGENESIS
·
2024
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IF 3
Zhanbo Sun,Lixian Liu,Hongyuan Liang,Lingyun Zhang
Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Herein, we investigated the role of nicotinamide mononucleotide (NMN) in HCC progression. HCC cells were treated with NMN (125, 250, and 500 μM), and then nicotinamide adenine dinucleotide (NAD + ) and NADH levels in HCC cells were measured to calculate NAD + /NADH ratio. Cell proliferation, apoptosis, autophagy and ferroptosis were determined. AMPK was knocked down to confirm the involvement of AMPK/mTOR signaling. Furthermore, tumor-inhibitory effect of NMN was investigated in xenograft models. Exposure to NMN dose-dependently increased NAD + level and NAD + /NADH ratio in HCC cells. After NMN treatment, cell proliferation was inhibited, whereas apoptosis was enhanced in both cell lines. Additionally, NMN dose-dependently enhanced autophagy/ferroptosis and activated AMPK/mTOR pathway in HCC cells. AMPK knockdown partially rescued the effects of NMN in vitro. Furthermore, NMN treatment restrained tumor growth in nude mice, activated autophagy/ferroptosis, and promoted apoptosis and necrosis in tumor tissues. The results indicate that NMN inhibits HCC progression by inducing autophagy and ferroptosis via AMPK/mTOR signaling. NMN may serve as a promising agent for HCC treatment.
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PubMed
高影响因子
PHYTOMEDICINE
·
2023
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IF 7.9
Gai Gao,Jie Zhao,Jing Ding,Shuyan Liu,Yanyan Shen,Changxin Liu,Huifen Ma,Yu Fu,Jiangyan Xu,Yiran Sun,Xiaowei Zhang,Zhenqiang Zhang,Zhishen Xie
Background The occurrence of hyperlipidemia is significantly influenced by lipid synthesis, which is regulated by sterol regulatory element binding proteins (SREBPs), thus the development of drugs that inhibit lipid synthesis has become a popular treatment strategy for hyperlipidemia. Alisol B (ALB), a triterpenoid compound extracted from Alisma , has been reported to ameliorate NASH and slow obesity. However, the effect of ALB on hyperlipidemia and mechanism are unclear. Purpose To examine the therapeutic impact of ALB on hyperlipidemia whether it inhibits SREBPs to reduce lipid synthesis. Study Design HepG2, HL7702 cells, and C57BL/6J were used to explore the effect of ALB on hyperlipidemia and the molecular mechanism in vivo and in vitro . Methods Hyperlipidemia models were established using western diet (WD)-fed mice in vivo and oleic acid (OA)-induced hepatocytes in vitro . Western blot, real-time PCR and other biological methods verified that ALB regulated AMPK/mTOR/SREBPs to inhibit lipid synthesis. Cellular thermal shift assay (CETSA), molecular dynamics (MD), and ultrafiltration-LC/MS analysis were used to evaluate the binding of ALB to VDAC1. Results ALB decreased TC, TG, LDL-c, and increased HDL-c in blood, thereby ameliorating liver damage. Gene set enrichment analysis (GSEA) indicated that ALB inhibited the biosynthesis of cholesterol and fatty acids. Consistently, ALB inhibited the protein expression of n-SREBPs and downstream genes. Mechanistically, the impact of ALB on SREBPs was dependent on the regulation of AMPK/mTOR, thereby impeding the transportation of SREBPs from endoplasmic reticulum to Golgi apparatus. Further investigations indicated that the activation of AMPK by ALB was independent on traditional CAMKK2 and LKB1. Instead, ALB resulted in a decrease in ATP levels and an increase in the ratios of ADP/ATP and AMP/ATP. CETSA, MD, and ultrafiltration-LC/MS analysis indicated that ALB interacted with VDAC1. Molecular docking revealed that ALB directly bound to VDAC1 by forming hydrogen bonds at the amino acid sites S196 and H184 in the ATP-binding region. Importantly, the thermal stabilization of ALB on VDAC1 was compromised when VDAC1 was mutated at S196 and H184, suggesting that these amino acids played a crucial role in the interaction. Conclusion Our findings reveal that VDAC1 serves as the target of ALB, leading to the inhibition of lipid synthesis, presents potential target and candidate drugs for hyperlipidemia.
研究领域:
药理学
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分子生物学
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生物化学
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细胞生物学
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代谢
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2025
·Vol. 15
·期 1
·1-15
·
IF 3.9
Xia Hong,Tai Xue-jiao,Cheng Wang,Wu Yi,He Dan,Wang Li-feng,Liu Hao,Zhang Shen-yi,Sun Yu-ting,Liu Hang-zhi,Liu Dan-dan,Zhao Hu-zi,Ji Fu-yun,Li Xi-hua
Small cell lung cancer (SCLC) is a therapeutically challenging disease. Metformin, an effective agent for the treatment of type 2 diabetes, has been shown to have antitumour effects on many cancers, including non-small cell lung cancer (NSCLC) and breast cancer. Currently, the antitumour effects of metformin on SCLC and the underlying molecular mechanisms remain unclear. CCK-8, EdU, colony formation, flow cytometry, immunofluorescence, molecular docking, western blotting, nude mouse transplanted tumour model, and immunohistochemistry experiments were conducted to analyse gene functions and the underlying mechanism involved. In vitro experiments demonstrated that metformin inhibited the growth of SCLC cells (H446, H526, H446/DDP and H526/DDP), which was confirmed in xenograft mouse models in vivo. Additionally, metformin induced cell cycle arrest, apoptosis, and autophagy in these SCLC cells. The molecular docking results indicated that metformin has a certain binding affinity for EGFR. The western blotting results revealed that metformin decreased the expression of EGFR, p-EGFR, AKT, and p-AKT, which could be reversed by EGF and SC79. Moreover, metformin activated AMPK and inactivated mTOR, and compound C and SC79 increased the levels of p-mTOR. Metformin can not only enhance the antitumour effect of cisplatin but also alleviate the toxic effects of cisplatin on the organs of xenograft model animals. In summary, the current study revealed that metformin inhibits the growth of SCLC by inducing autophagy and apoptosis via suppression of the EGFR/AKT/AMPK/mTOR pathway. Metformin might be a promising candidate drug for combination therapy of SCLC.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
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2022
·Vol. 78
·期 1
·213-227
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IF 5.08
Zhang Haihua,Lang Wuying,Liu Xin,Bai Jiangsong,Jia Qinghui,Shi Qiumei
Ulcerative colitis (UC) is a recurrent chronic inflammatory disease. The symptom of UC is mainly diarrhea including bloody stools. Increasing evidence has suggested that procyanidin A1 (PCA1) exerts an anti-inflammatory effect in several diseases. However, the role of PCA1 in UC is still a mystery. In our study, we explored the effect of PCA1 in dextran sulfate sodium (DSS)–induced UC mice and lipopolysaccharide (LPS)-stimulated HT-29 and IEC-6 cells. Then, cell proliferation, apoptosis, the production of proinflammatory cytokines, and autophagy-related markers were determined. Furthermore, the AMPK/mTOR/p70S6K signaling pathway was assayed by Western blot assay. In in vivo study, we found that PCA1 administration alleviated DSS-induced UC, as evidenced by reducing weight loss, clinical scores, colon weight/length ratio, histological damage, proinflammatory cytokines, and apoptosis. Moreover, we showed that the expression of Beclin-1 and LC3II/I ratio was increased, whereas the level of p62 was decreased after PCA1 treatment in vivo . Meanwhile, the reduced AMP/ATP ratio, enhanced expression of p-AMPK, and decreased p-p70S6K and p-mTOR levels indicate the activation of AMPK/mTOR/p70S6K signaling pathway. In in vitro study, PCA1 promoted cell proliferation and inhibited cell apoptosis in LPS-stimulated HT-29 and IEC-6 cells. Pro-inflammatory cytokines and autophagy-related factors exhibited the same trend as in in vivo results. Mechanically, PCA1 activated the AMPK/mTOR/p70S6K signaling pathway. The treatment with an AMPK inhibitor compound C significantly reversed the anti-inflammatory effect of PCA1 in LPS-stimulated cells. Taken together, these data indicated that PCA1 alleviated UC through induction of AMPK/mTOR/p70S6K-mediated autophagy.
研究领域:
胃肠病学
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药理学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 5.4
Xing-lan Ye,Ling-shuai Zeng,Qiang Liu,Wen-cheng Xu,Hong Liu,Hong Cheng,Wen-xiao Zheng,Xiao-qin Wang,Xue Xue
Ethnopharmacological relevance Huaiqihuang granule (HQH) is a traditional Chinese herbal formula comprising Trametes robiniophila Murr. , Lycii Fructus ., and Polygonatum sibiricum Red. This granule can nourish Qi and Yin, improve blood circulation and remove blood stasis. HQH has been extensively used to improve immune-mediated kidney diseases, such as IgA vasculitis nephritis (IgAVN). However, its renal protective mechanism remains elusive. Aim of the study This study investigated whether HQH ameliorates IgAVN by modulating the AMPK/mTOR-mediated autophagy pathway. Materials and methods The IgAVN mouse model was established using gliadin sensitization and India ink-mediated reticuloendothelial blockade (n = 10/group). The model mice were then treated for 4 weeks with low/high-dose HQH (4/8 g/kg/day) or dexamethasone (2.5 mg/kg/day). For in vitro analyses, human mesangial cells (HMCs) were first stimulated with aggregated IgA1 (aIgA1, 25 μg/mL) and then treated with the optimal concentration of HQH-containing serum (40 %). Furthermore, biochemical indices assays, renal histopathology, and immunofluorescence analysis of IgA deposition were performed. Moreover, autophagy levels were evaluated by assessing the expression of autophagy-related proteins, MDC staining, and mCherry-EGFP-LC3 transfection. Western blot and immunofluorescence were carried out to assess the levels of the AMPK/mTOR pathway proteins and proliferation markers. Results The results showed that HQH treatment significantly reduced 24-h urinary protein and serum IgA levels, but improved renal histopathology in IgAVN mice. Furthermore, HQH activated autophagy by upregulating p-AMPKα, LC3-Ⅱ/LC3-Ⅰ, and Beclin1, while inhibiting p-mTOR/mTOR and p62. Moreover, in HMCs, 40 % HQH-containing serum optimally inhibited aIgA1-induced mesangial proliferation and increased autophagic levels, as evidenced by the quantitative increase in autophagy activity and mean fluorescence intensity of MDC. However, these effects were blocked by AMPK inhibition. Conclusion This study showed that HQH alleviates IgAVN by upregulating AMPK/mTOR-mediated autophagy, inhibiting mesangial cell proliferation, and mitigating renal injury. These findings suggest that HQH has therapeutic potential for IgAVN and link autophagy modulation to IgAVN treatment.
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高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2021
·
IF 6.291
Min Kang,Jie Luo,Ling Zhao,Fei Shi,Gang Ye,Xiaoli He,Suqi Hao,Dan Yang,Helin Chen,Hongrui Guo,Yinglun Li,Huaqiao Tang
Nano-copper (nano-Cu) is widely used in the pharmaceutical field as well as a feed additive for animals owing to its unique physicochemical characteristics and bioactivities. In our previous study, nano-Cu was found to hamper fetal development; however, the toxicity of nano-Cu and its effects in placental function have not been elucidated. Therefore, we investigated the toxic effects of nano-Cu using rat placenta. Pregnant Sprague-Dawley rats were orally exposed to different copper sources from the third day of gestation (GD 3) to GD 18. We found that nano-Cu (180 mg/kg) and CuCl 2 .2 H 2 O increased the accumulation of copper. Besides, nano-Cu and CuCl 2 .2 H 2 O disrupted the placental morphology and induced oxidative stress. Micro-copper (micro-Cu) caused similar toxicity in the placenta, but its effects were weaker than that of nano-Cu and CuCl 2 .2 H 2 O. In addition, exposure to nano-Cu (180 mg/kg) and CuCl 2 .2 H 2 O induced inflammation in the rat placenta. Furthermore, nano-Cu, micro-Cu, and CuCl 2 .2 H 2 O upregulated the expression of the autophagy-related proteins, Beclin-1 and LC3 II/ LC3 I, and downregulated that of p62. Moreover, nano-Cu, micro-Cu, and CuCl 2 .2 H 2 O downregulated the protein expression of PI3K, p-AKT/AKT, and p-mTOR/mTOR in rat placentas, whereas the protein expression of p-AMPK/AMPK was upregulated. Taken together, our data indicated that prenatal exposure to nano-Cu induced autophagy via the PI3K/AKT/mTOR and AMPK/mTOR pathways, which associated with oxidative stress and inflammation in rat placenta.
研究领域:
毒理学
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药理学
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生殖生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）