The toxic effects of microcystin-LR on mouse lungs and alveolar type II epithelial cells

Wang, Cong; Gu, Song; Yin, Xiaoqin; Yuan, Mingming; Zou, Xiang; Li, Zutong; Cao, Honghui; Meng, Xiannan; Hu, Kebin; Han, Xiaodong

doi:10.1016/j.toxicon.2016.03.007

Cited by 32 publications

(19 citation statements)

References 37 publications

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“…The chronic low-dose of MC-LR exposure resulted to alveolar collapse, lung cell apoptosis and breach of cell junction integrity. ATII cells were also capable to uptake MC-LR and induced apoptosis and disrupted cell junction integrity [52]. Chronic oral administration of MC-LR also resulted in mitochondrial DNA (mtDNA) neuron damage and histopathological abnormalities as well as mtDNA damage were evident in the hippocampus and cerebral cortex with distinct effects on these two brain regions [53].…”

Section: Toxicity and Carcinogenicitymentioning

confidence: 99%

A Mini Review on Microcystins and Bacterial Degradation

Massey

Yang

2020

Toxins

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Microcystins (MCs) classified as hepatotoxic and carcinogenic are the most commonly reported cyanobacterial toxins found in the environment. Microcystis sp. possessing a series of MC synthesis genes (mcyA-mcyJ) are well documented for their excessive abundance, numerous bloom occurrences and MC producing capacity. About 246 variants of MC which exert severe animal and human health hazards through the inhibition of protein phosphatases (PP1 and PP2A) have been characterized. To minimize and prevent MC health consequences, the World Health Organization proposed 1 µg/L MC guidelines for safe drinking water quality. Further the utilization of bacteria that represent a promising biological treatment approach to degrade and remove MC from water bodies without harming the environment has gained global attention. Thus the present review described toxic effects and bacterial degradation of MCs.

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Section: Toxicity and Carcinogenicitymentioning

confidence: 99%

A Mini Review on Microcystins and Bacterial Degradation

Massey

Yang

2020

Toxins

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“…MC-LR-induced hepatotoxicity occurs by inhibiting protein phosphatase 1 and 2A (PP1 and PP2A) and inducing the production of ROS, followed by the destroying the cell cytoskeleton, eventually leads to liver cells necrosis and apoptosis [10,12]. In addition to the damage to the liver, some studies revealed that MCs also can cause harm to the intestines, brain, gonad, lung, and heart [13][14][15][16][17]. Recently, MCs have been reported to have penetrated renal cells in an OATPs dependent manner, subsequently promoting the accumulation of MC-LR [11,18].…”

Section: Introductionmentioning

confidence: 99%

Effects of Chronic Exposure to Microcystin-LR on Kidney in Mice

Huang

et al. 2019

IJERPH

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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.

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“…The results of our study are mostly consistent with findings of Wang et al [25], who found no significant effect of 10 µM MC-LR on viability in A549 human non-small lung cancer cells following 24-h exposure. On the contrary, Li et al [29] found that 10 µM MC-LR significantly reduced (EC50) cell survival in HBE cells after 24 h, and concentrations ≥50 nM were cytotoxic to immortalized murine alveolar type II cell line [45]. To compare with other epithelial cell lines, a decreased viability of rat Sertoli cells was found after 24-h exposure to 8-32 µM MC-LR [61].…”

Section: Discussionmentioning

confidence: 99%

“…However, the toxicological tipping point of the adaptive stress response may be surpassed with further cyanotoxin concentration increase and adverse effects on bronchial epithelial layers might be expected, as shown for CYN [67]. In addition, MC-LR-induced reduction of viability in murine epithelial alveolar type II (ATII) cells was accompanied by a dose-dependent decrease of TEER values and reduced expression of tight junction proteins (e.g., ZO-1, occludin) [45]. MC-LR also decreased the expression of tight junction proteins in murine Sertoli cells [69].…”

Section: Discussionmentioning

confidence: 99%

“…X. Li et al, 2016 [43] Inhalation (7 days) Degeneration and necrosis of nasal respiratory epithelium, neutrophilic inflammation Benson et al, 2005 [44] Additionally, Wang et al [45] observed decreased levels of cytoskeletal components leading to alterations in cell-cell communication in a dose-dependent manner, increased activation of MAPK-ERK1/2 and Akt, but no significant changes in inflammatory markers (IL-1, IL-6, nor TNF-α) in the mice alveolar type II epithelial cells. The relevance and importance to study the effects of MC-LR in the lungs is underlined by the fact that MC-LR influences tight junction proteins that play an important role in the alveolar epithelial barrier function [46,47].…”

Section: Mc-lr Administration Respiratory-related Symptoms Referencementioning

confidence: 99%

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Microcystin-LR Does Not Alter Cell Survival and Intracellular Signaling in Human Bronchial Epithelial Cells

Brózman

Kubíčková

Babica

et al. 2020

Toxins

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Changes in ecological and environmental factors lead to an increased occurrence of cyanobacterial water blooms, while secondary metabolites-producing cyanobacteria pose a threat to both environmental and human health. Apart from oral and dermal exposure, humans may be exposed via inhalation and/or swallowing of contaminated water and aerosols. Although many studies deal with liver toxicity, less information about the effects in the respiratory system is available. We investigated the effects of a prevalent cyanotoxin, microcystin-LR (MC-LR), using respiratory system-relevant human bronchial epithelial (HBE) cells. The expression of specific organic-anion-transporting polypeptides was evaluated, and the western blot analysis revealed the formation and accumulation of MC-LR protein adducts in exposed cells. However, MC-LR up to 20 µM neither caused significant cytotoxic effects according to multiple viability endpoints after 48-h exposure, nor reduced impedance (cell layer integrity) over 96 h. Time-dependent increase of putative MC-LR adducts with protein phosphatases was not associated with activation of mitogen-activated protein kinases ERK1/2 and p38 during 48-h exposure in HBE cells. Future studies addressing human health risks associated with inhalation of toxic cyanobacteria and cyanotoxins should focus on complex environmental samples of cyanobacterial blooms and alterations of additional non-cytotoxic endpoints while adopting more advanced in vitro models.Keywords: microcystin-LR; human bronchial epithelial cells; in vitro; HBE1; 16HBE14o-, mitogen-activated protein kinase; cytotoxicity; OATP Key Contribution:The study demonstrated the uptake of microcystin-LR into human bronchial epithelial cells HBE1 and 16HBE14o-. No significant changes in the cell viability, impedance (cell layer integrity) or activation of MAPKs ERK1/2 and p38 were detected in multiple exposure and concentration scenarios.

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The toxic effects of microcystin-LR on mouse lungs and alveolar type II epithelial cells

Cited by 32 publications

References 37 publications

A Mini Review on Microcystins and Bacterial Degradation

A Mini Review on Microcystins and Bacterial Degradation

Effects of Chronic Exposure to Microcystin-LR on Kidney in Mice

Microcystin-LR Does Not Alter Cell Survival and Intracellular Signaling in Human Bronchial Epithelial Cells

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