Long-term environmental levels of microcystin-LR exposure induces colorectal chronic inflammation, fibrosis and barrier disruption via CSF1R/Rap1b signaling pathway

Yang, Yue; Wang, Hui; Wang, Xiaoyan; Chen, Ling; Liu, Wenya; Cai, Danping; Deng, Shuxiang; Chu, Hanyu; Liu, Ying; Feng, Xiangling; Chen, Jihua; Chen, Mengshi; Wang, Chengkun; Liu, Ran; Pu, Yuepu; Zhang, Ding; Cao, Deliang; Long, Dongyang; Cao, Yi

doi:10.1016/j.jhazmat.2022.129793

Cited by 37 publications

(43 citation statements)

References 58 publications

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“…MC-LR and Cd share some common mechanisms, such as the promotion of intracellular reactive oxygen species (ROS) formation, inhibition of protein phosphatase activities, and disruption of the cytoskeleton and oxidative phosphorylation system, leading to inflammation, apoptosis, and injury. − It is well known that MC-LR is a highly potent and specific inhibitor of protein phosphatase 1/2A (PP1/2A), which can cause the imbalance of phosphorylation/dephosphorylation of key control proteins, including PI3K/AKT, leading to cytoskeleton destruction and apoptosis. , Interestingly, our study also found that long-term MC-LR exposure can cause renal inflammation and injury via the activation of the PI3K/AKT/mTOR signaling pathway. Previous studies have reported that Cd could induce ROS, inhibit PP2A and PP5, and activate the PI3K/AKT pathway, leading to pyroptosis in duck renal tubular epithelial cells. − Therefore, we reasonably speculated the combined mechanisms of nephrotoxicity of MC-LR and Cd.…”

Section: Discussionmentioning

confidence: 99%

Microcystin-LR Combined with Cadmium Exposures and the Risk of Chronic Kidney Disease: A Case–Control Study in Central China

Feng

Deng

Tang

et al. 2022

Environ. Sci. Technol.

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Increasing evidence indicates that exposure to microcystin-LR (MC-LR) can cause kidney damage. However, the association between MC-LR exposure and chronic kidney disease (CKD) risk in humans has not been studied. Therefore, we conducted a population-based case–control study involving 135 CKD cases and 135 matched controls in central China and analyzed the effects of MC-LR alone as well as combined with the known risk factor cadmium (Cd). Compared to the lowest quartile of MC-LR exposure, the highest quartile had a 2.82-fold (95% confidence interval [CI]: 1.37, 5.83) significantly increased risk for CKD, displaying a dose–response relationship (p trend < 0.05). Our animal study also showed that MC-LR exposure induced kidney injury via the PI3K/AKT/mTOR signaling pathway. Comparing the highest Cd quartile to the lowest, the adjusted odds ratio for CKD was 3.43 (95% CI: 1.42, 8.27), exhibiting a dose–response relationship (p trend < 0.05). Furthermore, a positive additive interaction was observed between MC-LR and Cd (relative excess risk due to interaction = 2.34, 95% CI: 0.30, 4.39; attributable proportion of interaction = 0.68, 95% CI: 0.37, 0.99). Our study firstly revealed that MC-LR exposure is an independent risk factor for CKD and has a synergistic relationship with Cd. MC-LR and Cd exposures are associated with CKD risk in a dose–response manner.

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Section: Discussionmentioning

confidence: 99%

Microcystin-LR Combined with Cadmium Exposures and the Risk of Chronic Kidney Disease: A Case–Control Study in Central China

Feng

Deng

Tang

et al. 2022

Environ. Sci. Technol.

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“…Additionally, a subset of the samples should be analyzed by reference untargeted and targeted LC-MS methods to unequivocally identify and quantify the occurrence of the different MC variants. These recommendations are particularly relevant considering the possible role of MC-LR as a carcinogen [ 22 ] as well as other serious possible chronic effects in the reproductive system, kidney, and intestine [ 23 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…The Working Group on the Evaluation of Carcinogenic Risks to Humans (IARC) classified MC-LR as possibly carcinogenic to humans, Group 2B [ 22 ]. Other possible chronic effects include the induction of reproductive toxicity [ 23 ], chronic kidney disease [ 24 ] as well as colorectal chronic inflammation and fibrosis [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Determination of Microcystins in Fish Tissue by ELISA and MALDI-TOF MS Using a Highly Specific Single Domain Antibody

Badagian

Schirmer

Pérez-Parada

et al. 2023

Toxins

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The development of simple, reliable, and cost-effective methods is critically important to study the spatial and temporal variation of microcystins (MCs) in the food chain. Nanobodies (Nbs), antigen binding fragments from camelid antibodies, present valuable features for analytical applications. Their small antigen binding site offers a focused recognition of small analytes, reducing spurious cross-reactivity and matrix effects. A high affinity and broad cross-reactivity anti-MCs-Nb, from a llama antibody library, was validated in enzyme linked immunosorbent assay (ELISA), and bound to magnetic particles with an internal standard for pre-concentration in quantitative-matrix-assisted laser desorption ionization-time of flight mass spectrometry (Nb-QMALDI MS). Both methods are easy and fast; ELISA provides a global result, while Nb-QMALDI MS allows for the quantification of individual congeners and showed excellent performance in the fish muscle extracts. The ELISA assay range was 1.8–29 ng/g and for Nb-QMALDI, it was 0.29–29 ng/g fish ww. Fifty-five fish from a MC-containing dam were analyzed by both methods. The correlation ELISA/sum of the MC congeners by Nb-QMALDI-MS was very high (r Spearman = 0.9645, p < 0.0001). Using ROC curves, ELISA cut-off limits were defined to accurately predict the sum of MCs by Nb-QMALDI-MS (100% sensitivity; ≥89% specificity). Both methods were shown to be simple and efficient for screening MCs in fish muscle to prioritize samples for confirmatory methods.

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“…While microcystin is commonly observed in cyanobacterial blooms, the presence of saxitoxin, anatoxin, and cylindrospermopsin are less common and understudied, and may be increasing in frequency in freshwater systems in North America (Christensen & Khan, 2020;Cruz et al, 2013;Testai et al, 2016). With the continuous production of cyanotoxins at LoW, the likelihood of long-term, low dosage, exposure may have broad health impacts on those who rely on LoW for drinking water (Yang et al, 2022;Zhao et al, 2020). Thus, from a management perspective it is important to understand who is responsible for each toxin produced to develop mitigation strategies.…”

Section: Potential Toxigenic Cyanobacterial Species In Low Bloomsmentioning

confidence: 99%

Nitrogen dynamics and fixation control cyanobacterial abundance, diversity, and toxicity in Lake of the Woods (USA, Canada)

Natwora

Heathcote

Edlund

et al. 2023

Preprint

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Our understanding of drivers of cyanobacterial harmful algal blooms (cHABs) is evolving, but it is apparent that not all lakes are created equal. Nitrogen (N) is an important component of all cHABs and is crucial for cyanotoxin production. It is generally assumed that external nitrogen inputs are the primary N source for cHABs. However, in northern lakes, nitrogen inputs are typically low which suggests that internal nitrogen cycling, through heterotrophic organic matter decomposition or nitrogen fixation, may play a significant role in cHAB development and sustainment. Using Lake of the Woods as a testbed, we quantified nutrients, cyanotoxins, nitrogen fixation, and the microbial community in the southern extent of the lake. During our temporal study, inorganic nitrogen species (NO3-+NO2- and NH4+) were either at very low concentrations or below detection, while phosphorus was in excess. These conditions resulted in nitrogen-deficient growth and thereby favored nitrogen-fixing cyanobacterial species. In response, nitrogen fixation rates increased exponentially throughout the summer and coincided with the Aphanizomenon sp. bloom. Despite nitrogen limitation, microcystin, anatoxin, saxitoxin, and cylindrospermopsin were all detected, with microcystin being the most abundant cyanotoxin detected. Microcystin concentrations were highest when free nitrogen was available and coincided with an increase in Microcystis. Together, our work suggests that internal nitrogen dynamics are responsible for the dominance of nitrogen-fixing cyanobacteria and that additions of nitrogen may increase the likelihood of other cyanobacterial species, currently at low abundance, to increase growth and cyanotoxin production.

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Long-term environmental levels of microcystin-LR exposure induces colorectal chronic inflammation, fibrosis and barrier disruption via CSF1R/Rap1b signaling pathway

Cited by 37 publications

References 58 publications

Microcystin-LR Combined with Cadmium Exposures and the Risk of Chronic Kidney Disease: A Case–Control Study in Central China

Microcystin-LR Combined with Cadmium Exposures and the Risk of Chronic Kidney Disease: A Case–Control Study in Central China

Determination of Microcystins in Fish Tissue by ELISA and MALDI-TOF MS Using a Highly Specific Single Domain Antibody

Nitrogen dynamics and fixation control cyanobacterial abundance, diversity, and toxicity in Lake of the Woods (USA, Canada)

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