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Microcystin-LR (MC-LR) is a potent hepatotoxin, but a few studies suggested that it might also induce nephrotoxicity. However, nephrotoxicity induced by prolonged oral exposure to MC-LR is unknown. The aim of this study was to evaluate the potential influence of MC-LR on the kidney in mice following chronic exposure to MC-LR. In this study, we evaluated the nephrotoxicity of MC-LR in mice drinking water at different concentrations (1, 30, 60, 90, and 120 μg/L) for 6 months for the first time. The results showed that the kidney weights and the kidney indexes of mice were not altered in the MC-LR treated mice, compared with the control group. In addition, the renal function indicators revealed that the serum creatinine (SCr) levels were not significant changes after exposure to MC-LR. The blood urea nitrogen (BUN) levels were markedly decreased after exposure to 90 and 120 μg/L MC-LR for 3 months. The BUN levels were lower than that of the control group after exposure to 120 μg/L MC-LR for 6 months. The histopathological investigation revealed enlarged renal corpuscles, widened of kidney tubules, and lymphocyte infiltration in the interstitial tissue and the renal pelvis after exposure to 60, 90, and 120 μg/L MC-LR. Consequently, our results suggested that long-term exposure to MC-LR might be one important risk of kidney injury, which will provide important clues for the prevention of renal impairment.
Xiping Yi; Shuaishuai Xu; Feiyu Huang; Cong Wen; Shuilin Zheng; Hai Feng; Jian Guo; Jihua Chen; Xiangling Feng; And Fei Yang. Effects of Chronic Exposure to Microcystin-LR on Kidney in Mice. International Journal of Environmental Research and Public Health 2019, 16, 5030 .
AMA StyleXiping Yi, Shuaishuai Xu, Feiyu Huang, Cong Wen, Shuilin Zheng, Hai Feng, Jian Guo, Jihua Chen, Xiangling Feng, And Fei Yang. Effects of Chronic Exposure to Microcystin-LR on Kidney in Mice. International Journal of Environmental Research and Public Health. 2019; 16 (24):5030.
Chicago/Turabian StyleXiping Yi; Shuaishuai Xu; Feiyu Huang; Cong Wen; Shuilin Zheng; Hai Feng; Jian Guo; Jihua Chen; Xiangling Feng; And Fei Yang. 2019. "Effects of Chronic Exposure to Microcystin-LR on Kidney in Mice." International Journal of Environmental Research and Public Health 16, no. 24: 5030.
The increasing cyanobacterial blooms have recently been considered a severe environmental problem. Microcystin-leucine arginine (MC-LR) is one of the secondary products of cyanobacteria metabolism and most harmful cyanotoxins found in water bodies. Studies show MC-LR negatively affects various human organs when exposed to it. The phenotype of the jejunal chronic toxicity induced by MC-LR has not been well described. The aim of this paper was to investigate the effects of MC-LR on the jejunal microstructure and expression level of inflammatory-related factors in jejunum. Mice were treated with different doses (1, 30, 60, 90 and 120 μg/L) of MC-LR for six months. The microstructure and mRNA expression levels of inflammation-related factors in jejunum were analyzed. Results showed that the microstructure of the jejunum was destroyed and expression levels of inflammation-related factors interleukin (IL)-1β, interleukin (IL)-8, tumor necrosis factor alpha, transforming growth factor-β1 and interleukin (IL)-10 were altered at different MC-LR concentrations. To the best of our knowledge, this is the first study that mice were exposed to a high dose of MC-LR for six months. Our data demonstrated MC-LR had the potential to cause intestinal toxicity by destroying the microstructure of the jejunum and inducing an inflammatory response in mice, which provided new insight into understanding the prevention and diagnosis of the intestinal diseases caused by MC-LR.
Linghui Cao; Feiyu Huang; Isaac Yaw Massey; Cong Wen; Shuilin Zheng; Shuaishuai Xu; Fei Yang. Effects of Microcystin-LR on the Microstructure and Inflammation-Related Factors of Jejunum in Mice. Toxins 2019, 11, 482 .
AMA StyleLinghui Cao, Feiyu Huang, Isaac Yaw Massey, Cong Wen, Shuilin Zheng, Shuaishuai Xu, Fei Yang. Effects of Microcystin-LR on the Microstructure and Inflammation-Related Factors of Jejunum in Mice. Toxins. 2019; 11 (9):482.
Chicago/Turabian StyleLinghui Cao; Feiyu Huang; Isaac Yaw Massey; Cong Wen; Shuilin Zheng; Shuaishuai Xu; Fei Yang. 2019. "Effects of Microcystin-LR on the Microstructure and Inflammation-Related Factors of Jejunum in Mice." Toxins 11, no. 9: 482.
Microcystin-LR is a cyclic heptapeptide hepatotoxin produced by harmful cyanobacteria. A panel of microRNAs containing miR-451a were found to be significantly changed in normal human liver cells HL7702 after exposure to microcystin-LR (MC-LR) in our previous study. However, the functions of miR-451a in hepatotoxicity induced by MC-LR remained unclear. The study aimed to investigate the impacts of miR-451a in HL7702 cells following treatment with 5 or 10 μM MC-LR. The comet assay indicated that MC-LR can influence Olive tail moment (OTM) in HL7702 cells. Furthermore, increase of miR-451a significantly repressed DNA damage and the protein expression level of γ-H2AX induced by MC-LR. Moreover, over-expression of miR-451a inhibited the expression level of p-AKT1 protein in cells following treatment by MC-LR. These results showed that miR-451a may protect from MC-LR-induced DNA damage by down-regulating the expression of p-AKT1, which provides new clues for the diagnosis and therapy policies for liver damage induced by MC-LR.
Lv Chen; Shu Yang; Cong Wen; Shuilin Zheng; Yue Yang; Xiangling Feng; Jihua Chen; Dan Luo; Ran Liu; Fei Yang. Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells. Toxins 2019, 11, 164 .
AMA StyleLv Chen, Shu Yang, Cong Wen, Shuilin Zheng, Yue Yang, Xiangling Feng, Jihua Chen, Dan Luo, Ran Liu, Fei Yang. Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells. Toxins. 2019; 11 (3):164.
Chicago/Turabian StyleLv Chen; Shu Yang; Cong Wen; Shuilin Zheng; Yue Yang; Xiangling Feng; Jihua Chen; Dan Luo; Ran Liu; Fei Yang. 2019. "Regulation of Microcystin-LR-Induced DNA Damage by miR-451a in HL7702 Cells." Toxins 11, no. 3: 164.
The occurrence of microcystin-LR(MC-LR) variant a known hepatotoxin constitutes a global public health concern. However, the molecular mechanisms underlying MC-LR-induced hepatotoxicity remain to be determined. The aim of this study was to investigate whether long noncoding RNAs (lncRNA) were involved in MC-LR-mediated hepatotoxicity using human normal liver cell line HL7702 to profile lncRNAs after 24 hr treatment with MC-LR. With the use of high-throughput sequencing techniques, data showed that the expression levels of 37, 33, 34, 35 lncRNA were significantly altered following exposure to 1, 2.5, 5, or 10 μM MC-LR, respectively. In particular, the expression levels of LINC00847, MIR22HG and LNC_00027 were markedly increased in all treatment groups. It is of interest that LNC_00027 was identified as a novel lncRNA. Quantitative real-time PCR (qPCR) was employed to determine the differentially expressed lncRNA levels. Analysis using Gene Ontology (GO) enrichment identified the functions of target genes involved in systems development, metabolism, and protein binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that MC-LR exposure upregulated some important signaling pathways including pathway in cancer, PI3K-AKT signaling and MAPK pathway. In summary, data indicate that the MC-LR-induced alterations in lncRNA may be associated with hepatotoxicity and that upregulation of LINC00847, MIR22HG and LNC_00027 may play important roles in the observed MC-mediated liver damage.
Cong Wen; Shu Yang; Shuilin Zheng; Xiangling Feng; Jihua Chen; Fei Yang. Analysis of long non-coding RNA profiled following MC-LR-induced hepatotoxicity using high-throughput sequencing. Journal of Toxicology and Environmental Health, Part A 2018, 81, 1165 -1172.
AMA StyleCong Wen, Shu Yang, Shuilin Zheng, Xiangling Feng, Jihua Chen, Fei Yang. Analysis of long non-coding RNA profiled following MC-LR-induced hepatotoxicity using high-throughput sequencing. Journal of Toxicology and Environmental Health, Part A. 2018; 81 (22):1165-1172.
Chicago/Turabian StyleCong Wen; Shu Yang; Shuilin Zheng; Xiangling Feng; Jihua Chen; Fei Yang. 2018. "Analysis of long non-coding RNA profiled following MC-LR-induced hepatotoxicity using high-throughput sequencing." Journal of Toxicology and Environmental Health, Part A 81, no. 22: 1165-1172.
Several studies previously demonstrated that microcystin (MC)-LR produced cytoskeletal damage, especially to actin filaments. However, the underlying mechanisms of MC-induced cytoskeletal reorganization remain to be determined. The aim of this study was to examine the effects of 5 or 10 µM MC-LR on microfilament depolarization and expression of microRNA-451a (miR-451a) which plays a crucial role in cellular processes including cell proliferation, apoptosis and tumorigenesis in HL7702 liver cells after 24 hr treatment. Data demonstrated that MC-LR increased microfilament depolarization, elevated phosphorylation levels of mitogen-activated protein kinase (MAPK/ERK1/2) and vasodilator-stimulated phosphoprotein (VASP) but lowered miR-451a RNA expression levels. These molecular processes were associated with no marked changes in total protein ERK1/2. Data demonstrate that transfection with miR-451a may not be effective in the presence of MC-LR as evidenced by the inability of excess microRNA to prevent toxin-induced inhibition of threonine protein phosphatases1 (PP1) and 2A (PP2A) and microfilament reorganization in HL7702 cells.
Fei Yang; Cong Wen; Shuilin Zheng; Shu Yang; Jihua Chen; Xiangling Feng. Involvement of MAPK/ERK1/2 pathway in microcystin-induced microfilament reorganization in HL7702 hepatocytes. Journal of Toxicology and Environmental Health, Part A 2018, 81, 1135 -1141.
AMA StyleFei Yang, Cong Wen, Shuilin Zheng, Shu Yang, Jihua Chen, Xiangling Feng. Involvement of MAPK/ERK1/2 pathway in microcystin-induced microfilament reorganization in HL7702 hepatocytes. Journal of Toxicology and Environmental Health, Part A. 2018; 81 (21):1135-1141.
Chicago/Turabian StyleFei Yang; Cong Wen; Shuilin Zheng; Shu Yang; Jihua Chen; Xiangling Feng. 2018. "Involvement of MAPK/ERK1/2 pathway in microcystin-induced microfilament reorganization in HL7702 hepatocytes." Journal of Toxicology and Environmental Health, Part A 81, no. 21: 1135-1141.
Microcystin-LR (MC-LR) is the most toxic and frequently detected monocyclic heptapeptide hepatotoxin produced by cyanobacteria, which poses a great threat to the natural ecosystem and public health. It is very important to seek environment-friendly and cost-efficient methods to remove MC-LR in water. In this study, the MC-degrading capacities of a novel indigenous bacterial community designated as YFMCD4 and the influence of environmental factors including various temperatures, MC concentrations and pH on the MC-degrading activities were investigated utilizing high-performance liquid chromatography (HPLC). In addition, the MC-degrading mechanism of YFMCD4 was also studied using HPLC coupled with a mass spectrometry equipped with electrospray ionization interface (HPLC-ESI-MS). The data showed MC-LR was completely removed at the maximum rate of 0.5 µg/(mL·h) under the optimal condition by YFMCD4. Two pure bacterial strains Alcaligenes faecalis and Stenotrophomonas acidaminiohila were isolated from YFMCD4 degraded MC-LR at a slower rate. The MC-degrading rates of YFMCD4 were significantly affected by different temperatures, pH and MC-LR concentrations. Two intermediates of a tetrapeptide and Adda appeared in the degradation process. These results illustrate that the novel YFMCD4 is one of the highest effective MC-degrading bacterial community, which can completely remove MC-LR and possesses a significant potential to treat water bodies contaminated by MC-LR.
Fei Yang; Jian Guo; Feiyu Huang; Isaac Yaw Massey; Ruixue Huang; Yunhui Li; Cong Wen; Ping Ding; Weiming Zeng; Geyu Liang. Removal of Microcystin-LR by a Novel Native Effective Bacterial Community Designated as YFMCD4 Isolated from Lake Taihu. Toxins 2018, 10, 363 .
AMA StyleFei Yang, Jian Guo, Feiyu Huang, Isaac Yaw Massey, Ruixue Huang, Yunhui Li, Cong Wen, Ping Ding, Weiming Zeng, Geyu Liang. Removal of Microcystin-LR by a Novel Native Effective Bacterial Community Designated as YFMCD4 Isolated from Lake Taihu. Toxins. 2018; 10 (9):363.
Chicago/Turabian StyleFei Yang; Jian Guo; Feiyu Huang; Isaac Yaw Massey; Ruixue Huang; Yunhui Li; Cong Wen; Ping Ding; Weiming Zeng; Geyu Liang. 2018. "Removal of Microcystin-LR by a Novel Native Effective Bacterial Community Designated as YFMCD4 Isolated from Lake Taihu." Toxins 10, no. 9: 363.
Microcystin-LR (MC-LR), the most common microcystin (MC) present in water is known to pose a significant threat to human health especially hepatotoxicity. However, the specific molecular mechanisms underlying MC-LR-induced hepatic cellular damage still remain to be determined. MicroRNAs (miRNAs) are known to play key roles in cellular processes including development, cell proliferation and responsiveness to stress. Thus, this study aimed to examine, whether miRNAs were involved in the observed MC-LR-mediated liver damage using miRNA profiling of a human normal liver cell line HL7702 using high-throughput sequencing techniques. Protein phosphatase 2A (PP2A) activity, an established biomarker of microcystin toxicity, was determined 24 hr following treatment with the algal toxin to confirm responsiveness. Data demonstrated that MC-LR significantly inhibited PP2A activity in a concentration-dependent manner with inhibitory concentration (IC50) value of 4.6 μM. Compared with control cells, treatment with MC-LR at concentrations of 1, 2.5, 5 or 10 μM significantly modified expression of levels of 3, 10, 9, and 99 miRNAs, respectively. Expression levels of miR-15b-3p were significantly increased in all 4 treatment groups, while miR-4521 expression levels were markedly reduced. In the case of miR-451a, 1, 5 or 10 μM also significantly lowered expression levels. However, a significant rise in miR-451a was noted in cells exposed to 2.5 μM toxin. The results obtained from miRNA differential expression levels were confirmed by real-time fluorescent quantitative PCR (qPCR). Gene Ontology (GO) enrichment analysis of hepatic cells demonstrated that miRNAs significantly altered were involved in systems development, metabolism, and protein binding. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis data showed that target genes of differentially expressed miRNAs in liver cells predominantly participated in mechanistic target of rapamycin kinase (mTOR), Ras, Ras-related protein 1 (Rap1), hypoxia inducible factor 1 (HIF-1), and cancer development. In summary, evidence indicates that MC-LR-induced hepatotoxicity may be associated with alterations in miRNAs. Evidence indicates that alterations in miR-451a, miR-4521 and miR-15b-3p may be involved in the observed MC-LR- induced hepatotoxicity
Shu Yang; Lv Chen; Cong Wen; Xian Zhang; Xiangling Feng; Fei Yang. MicroRNA expression profiling involved in MC-LR-induced hepatotoxicity using high-throughput sequencing analysis. Journal of Toxicology and Environmental Health, Part A 2017, 81, 89 -97.
AMA StyleShu Yang, Lv Chen, Cong Wen, Xian Zhang, Xiangling Feng, Fei Yang. MicroRNA expression profiling involved in MC-LR-induced hepatotoxicity using high-throughput sequencing analysis. Journal of Toxicology and Environmental Health, Part A. 2017; 81 (5):89-97.
Chicago/Turabian StyleShu Yang; Lv Chen; Cong Wen; Xian Zhang; Xiangling Feng; Fei Yang. 2017. "MicroRNA expression profiling involved in MC-LR-induced hepatotoxicity using high-throughput sequencing analysis." Journal of Toxicology and Environmental Health, Part A 81, no. 5: 89-97.