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A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Marine and Freshwater Toxins".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 21335

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Special Issue Editor

Prof. Dr. Fei Yang

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Guest Editor

1. School of Public Health, University of South China, Hengyang 421001, China
2. Xiangya School of Public Health, Central South University, Changsha 410078, China
Interests: microcystins; heavy metal; toxicity; biodegradation; bioadsorption

Special Issue Information

Dear Colleagues,

In recent decades, harmful cyanobacterial blooms and their secondary metabolites cyanotoxins have occurred all over the world because of global warming and water eutrophication. Microcystins widely distributed in freshwater are the common and most toxic cyanotoxins, which have caused great damage to aquatic ecosystems and threatened public health. To protect humans and animals from the toxicity of MC-LR, The World Health Organization (WHO) stipulated that the concentration of MC-LR in drinking water cannot exceed 1 μg/L. MC-LR can enter the intestine, transport through the blood stream, and distribute into various organs, so it is very important to investigate the toxic effect and mechanisms of microcystins against the liver, brain, kidney, lung, heart, and reproductive system. Moreover, how to control and remove MCs is a matter of great urgency worldwide. The utilization of bacteria is a promising approach to degrade and remove MC from waterbodies owing to its high efficiency, low cost, and environmental friendliness. Nonetheless, obtaining MC-degrading bacteria and understanding their MC-degrading mechanisms are great challenges.

The aim of this Special Issue entitled “Recent Advances in Microcystins” is to gather new findings about the toxic effects and mechanisms as well as the bacterial degradation of MCs. The resulting knowledge will provide deeper insights into the impact of MCs on human health and microbial degradation of MCs. Your contribution to this Special Issue will be greatly appreciated.

Dr. Fei Yang
Guest Editor

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Keywords

microcystins
toxicity
carcinogenicity
biodegradation
degradation mechanism

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Published Papers (9 papers)

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Research

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13 pages, 4061 KiB

Open AccessArticle

Cardiac Toxicity Induced by Long-Term Environmental Levels of MC-LR Exposure in Mice

by Canqun Yan, Ying Liu, Yue Yang, Isaac Yaw Massey, Linghui Cao, Muwaffak Al Osman and Fei Yang

Toxins 2023, 15(7), 427; https://doi.org/10.3390/toxins15070427 - 30 Jun 2023

Cited by 3 | Viewed by 1359

Abstract

Cyanobacterial blooms are considered a serious global environmental problem. Recent studies provided evidence for a positive association between exposure to microcystin-LR (MC-LR) and cardiotoxicity, posing a threat to human cardiovascular health. However, there are few studies on the cardiotoxic effects and mechanisms of long-term low-dose MC-LR exposure. Therefore, this study explored the long-term toxic effects and toxic mechanisms of MC-LR on the heart and provided evidence for the induction of cardiovascular disease by MC-LR. C57BL/6 mice were exposed to 0, 1, 30, 60, 90, and 120 μg/L MC-LR via drinking water for 9 months and subsequently necropsied to examine the hearts for microstructural changes using H&E and Masson staining. The results demonstrated fibrotic changes, and qPCR and Western blots showed a significant up-regulation of the markers of myocardial fibrosis, including TGF-β1, α-SMA, COL1, and MMP9. Through the screening of signaling pathways, it was found the expression of PI3K/AKT/mTOR signaling pathway proteins was up-regulated. These data first suggested MC-LR may induce myocardial fibrosis by activating the PI3K/AKT/mTOR signaling pathway. This study explored the toxicity of microcystins to the heart and preliminarily explored the toxic mechanisms of long-term toxicity for the first time, providing a theoretical reference for preventing cardiovascular diseases caused by MC-LR. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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13 pages, 6348 KiB

Open AccessArticle

Microcystin-LR-Exposure-Induced Kidney Damage by Inhibiting MKK6-Mediated Mitophagy in Mice

by Xueqiong Yao, Ying Liu, Yue Yang, Yafang Li, Na Hu, Fengmei Song and Fei Yang

Toxins 2023, 15(6), 404; https://doi.org/10.3390/toxins15060404 - 19 Jun 2023

Cited by 6 | Viewed by 1940

Abstract

Previous studies have reported that microcystin-LR (MC-LR) levels are highly correlated with abnormal renal function indicators, suggesting that MC-LR is an independent risk factor for kidney damage. However, the evidence for the exact regulation mechanism of MC-LR on kidney damage is still limited, and further in-depth exploration is needed. In addition, the mitochondria-related mechanism of MC-LR leading to kidney damage has not been elucidated. To this end, the present study aimed to further explore the mechanism of mitophagy related to kidney damage induced by MC-LR through in vitro and in vivo experiments. Male C57BL/6 mice were fed with a standard rodent pellet and exposed daily to MC-LR (20 μg/kg·bw) via intraperitoneal injections for 7 days. Moreover, HEK 293 cells were treated with MC-LR (20 μM) for 24 h. The histopathological results exhibited kidney damage after MC-LR exposure, characterized by structurally damaged nephrotomies, with inflammatory cell infiltration. Similarly, a significant increase in renal interstitial fibrosis was observed in the kidneys of MC-LR-treated mice compared with those of the control group (CT) mice. MC-LR exposure caused impaired kidney function, with markedly increased blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) levels in mice. Ultrastructural analysis exhibited obviously swollen, broken, and disappearing mitochondrial crests, and partial mitochondrial vacuoles in the MC-LR-treated HEK 293 cells. The Western blotting results demonstrated that exposure to MC-LR significantly increased the protein expressions of MKK6, p-p38, and p62, while the expression of mitophagy-related proteins was significantly inhibited in the kidneys of mice and HEK293 cells, including parkin, TOM20, and LC3-II, indicating the inhibition of mitophagy. Therefore, our data suggest that the inhibition of MKK6-mediated mitophagy might be the toxicological mechanism of kidney toxicity in mice with acute exposure to MC-LR. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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16 pages, 2212 KiB

Open AccessArticle

Microcystins Exposure Associated with Blood Lipid Profiles and Dyslipidemia: A Cross-Sectional Study in Hunan Province, China

by Shuidong Feng, Mengyue Cao, Peng Tang, Shuxiang Deng, Limou Chen, Yan Tang, Lemei Zhu, Xiang Chen, Zhijun Huang, Minxue Shen and Fei Yang

Toxins 2023, 15(4), 293; https://doi.org/10.3390/toxins15040293 - 18 Apr 2023

Cited by 1 | Viewed by 1868

Abstract

Increasing evidence from experimental research suggests that exposure to microcystins (MCs) may induce lipid metabolism disorder. However, population-based epidemiological studies of the association between MCs exposure and the risk of dyslipidemia are lacking. Therefore, we conducted a population-based cross-sectional study involving 720 participants in Hunan Province, China, and evaluated the effects of MCs on blood lipids. After adjusting the lipid related metals, we used binary logistic regression and multiple linear regression models to examine the associations among serum MCs concentration, the risk of dyslipidemia and blood lipids (triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)). Moreover, the additive model was used to explore the interaction effects on dyslipidemia between MCs and metals. Compared to the lowest quartile of MCs exposure, the risk of dyslipidemia [odds ratios (OR) = 2.27, 95% confidence interval (CI): 1.46, 3.53] and hyperTG (OR = 3.01, 95% CI: 1.79, 5.05) in the highest quartile was significantly increased, and showed dose–response relationships. MCs were positively associated with TG level (percent change, 9.43%; 95% CI: 3.53%, 15.67%) and negatively associated with HDL-C level (percent change, −3.53%; 95% CI: −5.70%, −2.10%). In addition, an additive antagonistic effect of MCs and Zn on dyslipidemia was also reported [relative excess risk due to interaction (RERI) = −1.81 (95% CI: −3.56, −0.05)], and the attributable proportion of the reduced risk of dyslipidemia due to the antagonism of these two exposures was 83% (95% CI: −1.66, −0.005). Our study first indicated that MCs exposure is an independent risk factor for dyslipidemia in a dose–response manner. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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11 pages, 1959 KiB

Open AccessArticle

Subchronic Microcystin-LR Aggravates Colorectal Inflammatory Response and Barrier Disruption via Raf/ERK Signaling Pathway in Obese Mice

by Yue Yang, Shuilin Zheng, Hanyu Chu, Can Du, Mengshi Chen, Mohammed Y. Emran, Jihua Chen, Fei Yang and Li Tian

Toxins 2023, 15(4), 262; https://doi.org/10.3390/toxins15040262 - 1 Apr 2023

Cited by 3 | Viewed by 1741

Abstract

Microcystin-LR (MC-LR) is an extremely poisonous cyanotoxin that poses a threat to ecosystems and human health. MC-LR has been reported as an enterotoxin. The objective of this study was to determine the effect and the mechanism of subchronic MC-LR toxicity on preexisting diet-induced colorectal damage. C57BL/6J mice were given either a regular diet or a high-fat diet (HFD) for 8 weeks. After 8 weeks of feeding, animals were supplied with vehicle or 120 μg/L MC-LR via drinking water for another 8 weeks, and their colorectal were stained with H&E to detect microstructural alterations. Compared with the CT group, the HFD and MC-LR + HFD-treatment group induced a significant weight gain in the mice. Histopathological findings showed that the HFD- and MC-LR + HFD-treatment groups caused epithelial barrier disruption and infiltration of inflammatory cells. The HFD- and MC-LR + HFD-treatment groups raised the levels of inflammation mediator factors and decreased the expression of tight junction-related factors compared to the CT group. The expression levels of p-Raf/Raf and p-ERK/ERK in the HFD- and MC-LR + HFD-treatment groups were significantly increased compared with the CT group. Additionally, treated with MC-LR + HFD, the colorectal injury was further aggravated compared with the HFD-treatment group. These findings suggest that by stimulating the Raf/ERK signaling pathway, MC-LR may cause colorectal inflammation and barrier disruption. This study suggests that MC-LR treatment may exacerbate the colorectal toxicity caused by an HFD. These findings offer unique insights into the consequences and harmful mechanisms of MC-LR and provide strategies for preventing and treating intestinal disorders. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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11 pages, 725 KiB

Open AccessArticle

Combination Effect of Microcystins and Arsenic Exposures on CKD: A Case-Control Study in China

by Hong Gao, Na Zhu, Shuxiang Deng, Can Du, Yan Tang, Peng Tang, Shuaishuai Xu, Wenya Liu, Minxue Shen, Xinhua Xiao and Fei Yang

Toxins 2023, 15(2), 144; https://doi.org/10.3390/toxins15020144 - 10 Feb 2023

Viewed by 1788

Abstract

Evidence has shown that exposure to environmental pollutants such as microcystins (MCs), arsenic (As), and cadmium (Cd) can lead to the occurrence and development of chronic kidney disease (CKD). There is a synergistic effect between MCs and Cd. However, the combined effect of MCs and As exposures on CKD remains unclear. In Hunan province, China, 135 controls and 135 CKD cases were enrolled in a case-control study. Serum MCs, plasma As and Cd concentrations were measured for all participants. We investigated the association between MCs/As and CKD risk using conditional logistic regression. The additive model explored the interaction effect, and the Bayesian kernel machine regression (BKMR) models investigated the combined effects of MCs, As, and Cd on CKD. The results showed that MCs and As were significantly associated with CKD risk. Participants in the highest MCs concentration had a 4,81-fold increased risk of CKD compared to those in the lowest quartile (95% confidence interval [CI]: 1,96 to 11,81). The highest quartile of As concentrations corresponded to an adjusted odds ratio of 3.40 (95% CI: 1.51, 7.65) relative to the lowest quartile. MCs/As and CKD risk exhibited significant dose–response correlations (all p for trend < 0.01). In addition, a positive interaction effect of MCs and As on CKD was also reported. The CKD risk due to interaction was 2.34 times (95% CI: 0.14, 4.54) relative to the CKD risk without interaction, and the attributable proportion of CKD due to interaction among individuals with both exposures was 56% (95% CI: 0.22, 0.91). In the BKMR, the combined effect of MCs, As, and Cd was positively associated with CKD. In conclusion, both MCs and As are independent risk factors for CKD, exerting a synergistic effect between them. Combined exposure to MCs, As, and Cd can increase the risk of CKD. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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15 pages, 3769 KiB

Open AccessArticle

MC-LR Aggravates Liver Lipid Metabolism Disorders in Obese Mice Fed a High-Fat Diet via PI3K/AKT/mTOR/SREBP1 Signaling Pathway

by Hanyu Chu, Can Du, Yue Yang, Xiangling Feng, Lemei Zhu, Jihua Chen and Fei Yang

Toxins 2022, 14(12), 833; https://doi.org/10.3390/toxins14120833 - 30 Nov 2022

Cited by 14 | Viewed by 2808

Abstract

Obesity, a metabolic disease caused by excessive fat accumulation in the body, has attracted worldwide attention. Microcystin-LR (MC-LR) is a hepatotoxic cyanotoxin which has been reportedly to cause lipid metabolism disorder. In this study, C57BL/6J mice were fed a high-fat diet (HFD) for eight weeks to build obese an animal model, and subsequently, the obese mice were fed MC-LR for another eight weeks, and we aimed to determine how MC-LR exposure affects the liver lipid metabolism in high-fat-diet-induced obese mice. The results show that MC-LR increased the obese mice serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), indicating damaged liver function. The lipid parameters include serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and liver TG, which were all increased, whilst the high-density lipoprotein cholesterol (HDL-c) was decreased. Furthermore, after MC-LR treatment, histopathological observation revealed that the number of red lipid droplets increased, and that steatosis was more severe in the obese mice. In addition, the lipid synthesis-related genes were increased and the fatty acid β-oxidation-related genes were decreased in the obese mice after MC-LR exposure. Meanwhile, the protein expression levels of phosphorylation phosphatidylinositol 3-kinase (p-PI3K), phosphorylation protein kinase B (p-AKT), phosphorylation mammalian target of rapamycin (p-mTOR), and sterol regulatory element binding protein 1c (SREBP1-c) were increased; similarly, the p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, and SREBP1/β-actin were significantly up-regulated in obese mice after being exposed to MC-LR, and the activated PI3K/AKT/mTOR/SREBP1 signaling pathway. In addition, MC-LR exposure reduced the activity of superoxide dismutase (SOD) and increased the level of malondialdehyde (MDA) in the obese mice’s serum. In summary, the MC-LR could aggravate the HFD-induced obese mice liver lipid metabolism disorder by activating the PI3K/AKT/mTOR/SREBP1 signaling pathway to hepatocytes, increasing the SREBP1-c-regulated key enzymes for lipid synthesis, and blocking fatty acid β-oxidation. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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10 pages, 1153 KiB

Open AccessArticle

Examination of Microcystin Adsorption by the Type of Plastic Materials Used during the Procedure of Microcystin Analysis

by Chan Seo, Joo Won Lee, Won-Kyo Jung, Yoon-Mi Lee, Seungjun Lee and Sang Gil Lee

Toxins 2022, 14(9), 625; https://doi.org/10.3390/toxins14090625 - 7 Sep 2022

Cited by 6 | Viewed by 2320

Abstract

The incidence of eutrophication is increasing due to fertilizer abuse and global warming. Eutrophication can induce the proliferation of cyanobacteria such as Microcystis, which produces microcystins. Microcystins are toxic to specific organs such as the liver and the heart. Thus, monitoring of microcystins is strongly required to control drinking water and agricultural product qualities. However, microcystins could be adsorbed by plastic materials during sample storage and preparation, hindering accurate analysis. Therefore, the current study examined the recovery rate of microcystins from six plastics used for containers and eight plastics used for membrane filters. Among the six plastics used for containers, polyethylene terephthalate showed the best recovery rate (≥81.3%) for 48 h. However, polypropylene, polystyrene, and high- and low-density polyethylenes showed significant adsorption after exposure for 1 hr. For membrane materials, regenerated cellulose (≥99.3%) showed the highest recovery rate of microcystins, followed by polyvinylidene fluoride (≥94.1%) and polytetrafluoroethylene (≥95.7%). The adsorption of microcystins appeared to be strongly influenced by various molecular interactions, including hydrophobic interaction, hydrogen bonding, and electrostatic interaction. In addition, microcystins’ functional residues seemed to be critical factors affecting their adsorption by plastic materials. The present study demonstrates that polyethylene terephthalate and regenerated cellulose membrane are suitable plastic materials for the analysis of microcystins. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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Review

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11 pages, 1186 KiB

Open AccessReview

Microcystin-LR in Primary Liver Cancers: An Overview

by Shen Gu, Mingxuemei Jiang and Bo Zhang

Toxins 2022, 14(10), 715; https://doi.org/10.3390/toxins14100715 - 20 Oct 2022

Cited by 14 | Viewed by 3065

Abstract

The cyanobacterial blooms produced by eutrophic water bodies have become a serious environmental issue around the world. After cellular lysing or algaecide treatment, microcystins (MCs), which are regarded as the most frequently encountered cyanobacterial toxins in fresh water, are released into water. Among all the variants of MCs, MC-LR has been widely studied due to its severe hepatotoxicity. Since 1992, various studies have identified the important roles of MC-LR in the origin and progression of primary liver cancers (PLCs), although few reviews have focused on it. Therefore, this review aims to summarize the major achievements and shortcomings observed in the past few years. Based on the available literature, the mechanisms of how MC-LR induces or promotes PLCs are elucidated in this review. This review aims to enhance our understanding of the role that MC-LR plays in PLCs and provides a rational approach for future applications. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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14 pages, 720 KiB

Open AccessReview

Immobilization of Microbes for Biodegradation of Microcystins: A Mini Review

by Jiajia Zhang, Jia Wei, Isaac Yaw Massey, Tangjian Peng and Fei Yang

Toxins 2022, 14(8), 573; https://doi.org/10.3390/toxins14080573 - 22 Aug 2022

Cited by 23 | Viewed by 3495

Abstract

Harmful cyanobacterial blooms (HCBs) frequently occur in eutrophic freshwater ecosystems worldwide. Microcystins (MCs) are considered to be the most prominent and toxic metabolites during HCBs. MCs may be harmful to human and animal health through drinking water and recreational water. Biodegradation is eco-friendly, cost-effective and one of the most effective methods to remove MCs. Many novel MC-degrading bacteria and their potential for MCs degradation have been documented. However, it is a challenge to apply the free MC-degrading bacterial cells in natural environments due to the long-term operational instability and difficult recycling. Immobilization is the process of restricting the mobility of bacteria using carriers, which has several advantages as biocatalysts compared to free bacterial cells. Biological water treatment systems with microbial immobilization technology can potentially be utilized to treat MC-polluted wastewater. In this review article, various types of supporting materials and methods for microbial immobilization and the application of bacterial immobilization technology for the treatment of MCs-contaminated water are discussed. This article may further broaden the application of microbial immobilization technology to the bioremediation of MC-polluted environments. Full article

(This article belongs to the Special Issue Recent Advances in Microcystins)

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