Chronic exposure to low concentration of MC-LR caused hepatic lipid metabolism disorder

Du, Chenglong; Zheng, Shuilin; Yang, Yue; Feng, Xiangling; Chen, Jihua; Tang, Yan; Wang, Hui

doi:10.1016/j.ecoenv.2022.113649

Cited by 25 publications

(10 citation statements)

References 44 publications

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“…It was found that MC-LR increased the levels of TNF-α and IL-6 in lung tissues, especially when mice were exposed for 12 months, accompanied by inflammatory cell infiltration. These data were similar to the results of MC-LR on mice brain, ovary, liver, lungs, etc. Thus, MC-LR-induced pneumonia may partially contribute to the disruption of the lung barrier.…”

Section: Discussionsupporting

confidence: 89%

Chronic Exposure to Environmentally Relevant Concentrations of Microcystin-Leucine Arginine Causes Lung Barrier Damage through PP2A Activity Inhibition and Claudin1 Ubiquitination

Liu

Zeng

Wang

et al. 2022

J. Agric. Food Chem.

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Microcystin-leucine arginine (MC-LR), ubiquitous in water and food, is a threat to public health. In the present study, after C57BL/6J mice were fed with environmental concentrations of MC-LR (0, 1, 30, 60, 90, and 120 μg/L) for 6, 9, and 12 months, it was found that MC-LR could enter into mouse lung tissues and cause microstructural damage, as shown by western blotting and HE staining. Electron microscopy examination showed that MC-LR could damage the lung barrier by disruption of the tight junctions, which was confirmed by the decreased expression of tight junction markers, including Occludin, Claudin1, and ZO-1. In addition, MC-LR also increased the ubiquitination of Claudin1, indicating that MC-LR could disrupt tight junctions by promoting the degradation of Claudin1. Furthermore, MC-LR increased the levels of TNF-α and IL-6 in mouse lung tissues, leading to pneumonia. Importantly, pretreatment with PP2A activator D-erythro-sphingosine (DES) was found to significantly alleviate MC-LR-induced decrease of Occludin and Claudin1 by inhibiting the P-AKT/Snail pathway in vitro. Together, this study revealed that chronic exposure to MC-LR causes lung barrier damage, which involves PP2A activity inhibition and enhancement of Claudin1 ubiquitination. This study broadens the awareness of the toxic effects of MC-LR on the respiratory system, which has deep implications for public health.

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Section: Discussionsupporting

confidence: 89%

Chronic Exposure to Environmentally Relevant Concentrations of Microcystin-Leucine Arginine Causes Lung Barrier Damage through PP2A Activity Inhibition and Claudin1 Ubiquitination

Liu

Zeng

Wang

et al. 2022

J. Agric. Food Chem.

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“…qRT-PCR was performed on a qTOWER3 Real-Time PCR System (Analytikjena, Germany) using ChamQ Universal SYBR qRT-PCR Master Mix (Vazyme, NanJing, China) with gene-specific primers. The melting curve was analyzed after the amplification stage was completed, and the relative mRNA levels were calculated using the 2 –ΔΔ Ct method …”

Section: Methodsmentioning

confidence: 99%

“…After incubation, the membranes were incubated with secondary antibodies (goat anti-mouse IgG [H + L] HRP conjugate or goat anti-rabbit IgG [H + L] HRP conjugate) for 1 h. An HRP substrate (Luminata Forte Western HRP Substrate; Millipore) was added to the membranes, and chemiluminescence was detected using the Bio-Rad imaging system. Using Image J software, the intensities of protein bands were quantified …”

Section: Methodsmentioning

confidence: 99%

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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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Effects of microcystin-LR on behavior, histopathology, oxidative stress, non-specific immunity and gene expression of red claw crayfish (Cherax quadricarinatus)

Lu,

Zhang,

Zheng

et al. 2023

Aquaculture Reports

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Chronic exposure to low concentration of MC-LR caused hepatic lipid metabolism disorder

Cited by 25 publications

References 44 publications

Chronic Exposure to Environmentally Relevant Concentrations of Microcystin-Leucine Arginine Causes Lung Barrier Damage through PP2A Activity Inhibition and Claudin1 Ubiquitination

Chronic Exposure to Environmentally Relevant Concentrations of Microcystin-Leucine Arginine Causes Lung Barrier Damage through PP2A Activity Inhibition and Claudin1 Ubiquitination

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

Effects of microcystin-LR on behavior, histopathology, oxidative stress, non-specific immunity and gene expression of red claw crayfish (Cherax quadricarinatus)

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