The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity

Chernoff, Neil; Hill, Donna; Lang, Johnsie R.; Schmid, Judy; Le, Thao Thanh; Farthing, Amy; Huang, Hwa

doi:10.3390/toxins12060403

Cited by 46 publications

(38 citation statements)

References 72 publications

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“…The key findings, summarized in Table 1 , are consistent with the conclusions about comparative MC congener acute toxicity reached in our previous 7 mg/kg single-dose study [ 48 ]. MCLA was the most toxic congener, with the 3 mg/kg LOAEL dose being hepatotoxic and also inducing significantly elevated BUN/creatinine ratios in females and decreased levels of serum glucose in both sexes.…”

Section: Discussionsupporting

confidence: 89%

“…This paper summarizes data evaluating dose responses of single oral exposures to MCLA, MCLR, MCLY, MCRR, and MCYR in the BALB/c mouse using toxicity endpoints indicative of hepatic toxicity and altered homeostasis. It follows a previous paper [ 48 ] that compared the toxicities of ten MC congeners after exposures to the single-dose level of 7 mg/kg of one of the five congeners summarized here as well as MCLF, MCLW, [Asp3]MCRR, [Asp3,Dhb7]MCRR, and MCWR. The data in the completed comparative MC congener study were used to select a starting dose range for determining acute exposure NOAELs and LOAELs based on live animal and organ observations, body and organ weights, and changes in serum components indicative of liver function and general homeostasis.…”

Section: Introductionmentioning

confidence: 99%

“…The data in the completed comparative MC congener study were used to select a starting dose range for determining acute exposure NOAELs and LOAELs based on live animal and organ observations, body and organ weights, and changes in serum components indicative of liver function and general homeostasis. The 7 mg/kg data for the MCLA, MCLY, MCRR, and MCYR, as well as part of the MCLR dose–response data, were also presented in [ 48 ].…”

Section: Introductionmentioning

confidence: 99%

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Dose–Response Study of Microcystin Congeners MCLA, MCLR, MCLY, MCRR, and MCYR Administered Orally to Mice

Chernoff

Hill

Lang

et al. 2021

Toxins

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Microcystins are common freshwater cyanobacterial toxins that affect liver function. The toxicities of five microcystin congeners (microcystin-LA (MCLA), MCLR, MCLY, MCRR, and MCYR) commonly observed in harmful algal blooms (HABs) were evaluated in BALB/c mice after a single oral administration of doses ranging from those that were no observed adverse effect levels (NOAELs) to lowest observed adverse effect levels (LOAELs). Animals were monitored for changes in behavior and appearance, and euthanized 24 h after dosing. Test endpoints included clinical changes, necropsy observations, and serum indicators of hepatic toxicity and general homeostasis. Doses were 0.5–7 mg/kg MCLA, 0.5–11 mg/kg MCLR, 1–7 mg/kg MCLY, 7–22 mg/kg MCRR, and 3–11 mg/kg MCYR. MCLA at 3 mg/kg elevated liver/body weight ratio and liver score, ALT, AST, and GLDH, indicating hepatic toxicity, reduced serum glucose and highly elevated total serum bilirubin. MCLR and MCLY induced similar effects with LOAELs of 5 mg/kg, although a greater extent and severity of effects were observed in MCLR animals. MCRR exposure at 22 mg/kg was associated with reduced serum glucose. MCYR induced scattered liver effects at 7 mg/kg and reduced serum glucose levels at 5 mg/kg. The results indicate significant differences in congener-induced toxicity after microcystin exposure.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dose–Response Study of Microcystin Congeners MCLA, MCLR, MCLY, MCRR, and MCYR Administered Orally to Mice

Chernoff

Hill

Lang

et al. 2021

Toxins

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“…To address differences in toxicity among MCs analogues some studies suggest to use the toxicity equivalency factor (TEF) approach which estimates the toxicity/potency of a MC analogue relative to the toxicity/potency of MC-LR ( Altaner et al., 2020 ; Garibo et al., 2014 ; Ikehara et al., 2009 ). However, the relative toxicities determined by in vitro ( Fischer et al., 2010 ; Garibo et al., 2014 ; Ikehara et al., 2009 ; Niedermeyer et al., 2014 ), in vivo ( Chen et al., 2006 ; Chernoff et al., 2020 ) or in silico predictions studies ( Altaner et al., 2020 ) are not consistent. Given the poor knowledge of mechanism of action and non-standardised toxicity studies based on single doses, intraperitoneal injections instead of oral administration and single toxins instead of multiple toxins, it is therefore difficult to define a TEF for the different MC variants.…”

Section: Resultsmentioning

confidence: 98%

Rapid uptake and slow depuration: Health risks following cyanotoxin accumulation in mussels?

Camacho‐Muñoz

Waack

Turner

et al. 2021

Environmental Pollution

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Freshwater cyanobacteria produce highly toxic secondary metabolites, which can be transported downstream by rivers and waterways into the sea. Estuarine and coastal aquaculture sites exposed to toxic cyanobacteria raise concerns that shellfish may accumulate and transfer cyanotoxins in the food web. This study aims to describe the competitive pattern of uptake and depuration of a wide range of microcystins (MC-LR, MC-LF, MC-LW, MC-LY, [Asp3]-MC-LR/[Dha7]-MC-LR, MC-HilR) and nodularins (NOD cyclic and linear) within the common blue mussel Mytilus edulis exposed to a combined culture of Microcystis aeruginosa and Nodularia spumigena into the coastal environment. Different distribution profiles of MCs/NODs in the experimental system were observed. The majority of MCs/NODs were present intracellularly which is representative of healthy cyanobacterial cultures, with MC-LR and NOD the most abundant analogues. Higher removal rate was observed for NOD (≈96%) compared to MCs (≈50%) from the water phase. Accumulation of toxins in M. edulis was fast, reaching up to 3.4 μg/g shellfish tissue four days after the end of the 3-days exposure period, with NOD (1.72 μg/g) and MC-LR (0.74 μg/g) as the dominant toxins, followed by MC-LF (0.35 μg/g) and MC-LW (0.31 μg/g). Following the end of the exposure period depuration was incomplete after 27 days (0.49 μg/g of MCs/NODs). MCs/NODs were also present in faecal material and extrapallial fluid after 24 h of exposure with MCs the main contributors to the total cyanotoxin load in faecal material and NOD in the extrapallial fluid. Maximum concentration of MCs/NODs accumulated in a typical portion of mussels (20 mussels, ≈4 g each) was beyond greater the acute, seasonal and lifetime tolerable daily intake. Even after 27 days of depuration, consuming mussels harvested during even short term harmful algae blooms in close proximity to shellfish beds might carry a high health risk, highlighting the need for testing.

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“…Similar differences between oral and i.p. administration were recently reported using other toxins such as mycrocystin [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

DSP Toxin Distribution across Organs in Mice after Acute Oral Administration

et al. 2021

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Okadaic acid (OA) and its main structural analogs dinophysistoxin-1 (DTX1) and dinophysistoxin-2 (DTX2) are marine lipophilic phycotoxins distributed worldwide that can be accumulated by edible shellfish and can cause diarrheic shellfish poisoning (DSP). In order to study their toxicokinetics, mice were treated with different doses of OA, DTX1, or DTX2 and signs of toxicity were recorded up to 24 h. Toxin distribution in the main organs from the gastrointestinal tract was assessed by liquid chromatography-mass spectrometry (LC/MS/MS) analysis. Our results indicate a dose-dependency in gastrointestinal absorption of these toxins. Twenty-four hours post-administration, the highest concentration of toxin was detected in the stomach and, in descending order, in the large intestine, small intestine, and liver. There was also a different toxicokinetic pathway between OA, DTX1, and DTX2. When the same toxin doses are compared, more OA than DTX1 is detected in the small intestine. OA and DTX1 showed similar concentrations in the stomach, liver, and large intestine tissues, but the amount of DTX2 is much lower in all these organs, providing information on DSP toxicokinetics for human safety assessment.

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The Comparative Toxicity of 10 Microcystin Congeners Administered Orally to Mice: Clinical Effects and Organ Toxicity

Cited by 46 publications

References 72 publications

Dose–Response Study of Microcystin Congeners MCLA, MCLR, MCLY, MCRR, and MCYR Administered Orally to Mice

Dose–Response Study of Microcystin Congeners MCLA, MCLR, MCLY, MCRR, and MCYR Administered Orally to Mice

Rapid uptake and slow depuration: Health risks following cyanotoxin accumulation in mussels?

DSP Toxin Distribution across Organs in Mice after Acute Oral Administration

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