Microcystin-LR Induced Immunotoxicity in Mammals

Lone, Yaqoob; Bhide, Mangla; Koiri, Raj Kumar

doi:10.1155/2016/8048125

Cited by 41 publications

(15 citation statements)

References 32 publications

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“…Besides reports of effects on gastrointestinal and hepatic cells, MC-LR is suspected to alter the immune response, especially in fish, in which most of the studies addressing immunotoxic effects have been done [107][108][109][110][111]. For example, exposure to MC-LR affected the immune response of medaka fish and induced sustained pathological changes in the GIT, liver, and other organs [108].…”

Section: Microcystin Effectsmentioning

confidence: 99%

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

et al. 2019

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Background: Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro-, and neurotoxicity, than for effects on the gastrointestinal tract and the associated lymphoid tissue. Main body: The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human health-relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects, or both. Furthermore, cyanobacterial bloom lipopolysaccharides, other less studied metabolites and their mixtures have been also implicated to have a role in gastrointestinal inflammation. Conclusion: The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. In addition, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites such as aeruginosins, have to be toxicologically evaluated at distinct levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, which can be expected in drinking water supplies.

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Section: Microcystin Effectsmentioning

confidence: 99%

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

et al. 2019

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“…MC-LR then exhibits its deleterious effects by inhibiting the activity of protein phosphatases 1 (PP1) and 2A (PP2A) and by increasing the production of reactive oxygen species (ROS) [10,11]. As a result, there is a hyperphosphorylation and pro-oxidative state induced by MC-LR, which leads to alterations in the cytoskeleton, OATP expression, mitogen-activated protein kinase (MAPK) activity, glycogen storage, and mitochondrial structure and function in addition to DNA damage, cellular disruption, endoplasmic reticulum dysfunction, inflammation and tumor growth [12,13,14,15,16,17,18,19,20].…”

Section: Introductionmentioning

confidence: 99%

Chronic Low Dose Oral Exposure to Microcystin-LR Exacerbates Hepatic Injury in a Murine Model of Non-Alcoholic Fatty Liver Disease

Lad

Breidenbach

et al. 2019

Toxins

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Microcystins are potent hepatotoxins that have become a global health concern in recent years. Their actions in at-risk populations with pre-existing liver disease is unknown. We tested the hypothesis that the No Observed Adverse Effect Level (NOAEL) of Microcystin-LR (MC-LR) established in healthy mice would cause exacerbation of hepatic injury in a murine model (Leprdb/J) of Non-alcoholic Fatty Liver Disease (NAFLD). Ten-week-old male Leprdb/J mice were gavaged with 50 μg/kg, 100 μg/kg MC-LR or vehicle every 48 h for 4 weeks (n = 15–17 mice/group). Early mortality was observed in both the 50 μg/kg (1/17, 6%), and 100 μg/kg (3/17, 18%) MC-LR exposed mice. MC-LR exposure resulted in significant increases in circulating alkaline phosphatase levels, and histopathological markers of hepatic injury as well as significant upregulation of genes associated with hepatotoxicity, necrosis, nongenotoxic hepatocarcinogenicity and oxidative stress response. In addition, we observed exposure dependent changes in protein phosphorylation sites in pathways involved in inflammation, immune function, and response to oxidative stress. These results demonstrate that exposure to MC-LR at levels that are below the NOAEL established in healthy animals results in significant exacerbation of hepatic injury that is accompanied by genetic and phosphoproteomic dysregulation in key signaling pathways in the livers of NAFLD mice.

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“…Human exposures to these toxins can lead to a variety of symptoms ranging from gastroenteritis, nausea, allergic reactions, and skin rashes in mild cases to hepatic injury and hemorrhage in more severe cases [4]. MCs have also been linked to tumor progression and are harmful to renal, immune, and reproductive systems [5][6][7][8]. Due to the potential harm to humans, the World Health Organization (WHO) has set the upper provisional guideline limit of 1 ng/mL for MC-LR in their Guidelines for Drinking Water Quality [9].…”

Section: Methods Optimizationmentioning

confidence: 99%

Measurement of Microcystin and Nodularin Activity in Human Urine by Immunocapture-Protein Phosphatase 2A Assay

Wharton

Cunningham

Schaefer

et al. 2019

Toxins

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Microcystins (MC) and nodularin (NOD) are toxins released by cyanobacteria during harmful algal blooms. They are potent inhibitors of protein phosphatases 1 and 2A (PP1 and PP2A) and cause a variety of adverse symptoms in humans and animals if ingested. More than 250 chemically diverse congeners of MCs have been identified, but certified reference materials are only available for a few. A diagnostic test that does not require each reference material for detection is necessary to identify human exposures. To address this need, our lab has developed a method that uses an antibody to specifically isolate MCs and NOD from urine prior to detection via a commercially available PP2A kit. This assay quantitates the summed inhibitory activity of nearly all MCs and NOD on PP2A relative to a common MC congener, microcystin-LR (MC-LR). The quantitation range for MC-LR using this method is from 0.050-0.500 ng/mL. No background responses were detected in a convenience set of 50 individual urines. Interday and intraday % accuracies ranged from 94%-118% and relative standard deviations were 15% or less, meeting FDA guidelines for receptor binding assays. The assay detected low levels of MCs in urines from three individuals living in close proximity to harmful algal blooms (HABs) in Florida.Keywords: microcystins; nodularin; protein phosphatase 2A; immunocapture; harmful algal bloom Key Contribution: This paper describes the development and subsequent validation of an immunocapture-protein phosphatase inhibition assay to detect and measure combined inhibitory activity of MCs and NOD in human urine. Low levels of MCs were detected in urine specimens from individuals living or working in close proximity to harmful algal blooms.

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Microcystin-LR Induced Immunotoxicity in Mammals

Cited by 41 publications

References 32 publications

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

Chronic Low Dose Oral Exposure to Microcystin-LR Exacerbates Hepatic Injury in a Murine Model of Non-Alcoholic Fatty Liver Disease

Measurement of Microcystin and Nodularin Activity in Human Urine by Immunocapture-Protein Phosphatase 2A Assay

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