Investigation of aMicrocystis aeruginosacyanobacterial freshwater harmful algal bloom associated with acute microcystin toxicosis in a dog

Abstract

Microcystin poisoning was diagnosed in a dog exposed to a Microcystis aeruginosa-dominated, freshwater, harmful algal bloom at Milford Lake, Kansas, which occurred during the summer of 2011. Lake water microcystin concentrations were determined at intervals during the summer, using competitive enzyme-linked immunosorbent assays, and indicated extremely high, localized microcystin concentrations of up to 126,000 ng/ml. Multiple extraction and analysis techniques were used in the determination of free and total microcystins in vomitus and liver samples from the poisoned dog. Vomitus and liver contained microcystins, as determined by enzyme-linked immunosorbent assays, and the presence of microcystin-LR was confirmed in vomitus and liver samples using liquid chromatography coupled with tandem mass spectrometry. Major toxic effects in a dog presented for treatment on the day following exposure included fulminant liver failure and coagulopathy. The patient deteriorated rapidly despite aggressive treatment and was euthanized. Postmortem lesions included diffuse, acute, massive hepatic necrosis and hemorrhage, as well as acute necrosis of the renal tubular epithelium. A diagnosis of microcystin poisoning was based on the demonstration of M. aeruginosa and microcystin-LR in the lake water, as well as in vomitus produced early in the course of the poisoning; the presence of microcystin-LR in liver tissue; and a typical clinical course including gastroenteritis and fulminant liver failure.

Microcystin-LR induced liver injury in mice and in primary human hepatocytes is caused by oncotic necrosis

“…bile acid toxicity, may be inherently more sensitive and have entirely different mechanisms (Woolbright et al, 2015). This is supported by the fact that humans seem to undergo significantly less hemorrhage than other mammalian exposures (Pouria et al, 1998; van der Merwe et al, 2012; Figure 1). As mice expire from hemorrhagic shock shortly after toxic MC-LR exposure, it is imperative to understand MC-LR toxicity in primary human hepatocytes due to their fidelity with the human condition, and the established role of cell death in MC-LR toxicity in humans.…”

“…In rat primary hepatocyte culture, exposure to MC-LR results in rapid mitochondrial dysfunction, and prototypical apoptosis (Ding et al, 2000). As such, apoptosis has become the most commonly cited mechanism for MC-LR induced cell death in most models (Kleppe et al, 2015; Chen and Xie, 2016); however, considerable alanine aminotransferase (ALT) release (van der Merwe et al, 2012), and hemorrhagic necrosis (Theiss et al, 1988; Bautista et al, 2015), have been consistently noted in pathological reports of animal exposure to MC-LR. Moreover, MCF-7 breast cancer cells with a defective caspase-3 enzyme, which are highly resistant to apoptosis, are sensitive to MC-LR (Fladmark et al, 1999).…”

Current approaches to cyanotoxin risk assessment and risk management around the globe

“…The primarily hepatotoxic micro-cystins – a family of more than 80 different congeners, commonly measured and expressed as total MCYST-LR equivalents – are probably the most widespread and best studied group of cyanotoxins (Dittmann et al, 2013; Ferrao-Filho and Kozlowsky-Suzuki, 2011; Ibelings and Havens, 2008; Kozlowsky-Suzuki et al, 2012). Data on the occurrence of other cyanotoxins are increasingly becoming available, particularly for cylindrospermopsin (CYN), neurotoxins like saxitoxin (STX) or anatoxins (ATX) (Metcalf et al, 2008; Seifert et al, 2007; van Apeldoorn et al, 2007; van der Merwe et al, 2012) and information on new classes arising (e.g. jamaicamides, Neilan et al, 2013).…”

“…To some extent toxin levels respond to environmental conditions so that the toxin content per cell may vary several fold (Neilan et al, 2013; van der Merwe et al, 2012; Wiedner et al, 2003); also the proportion of different MCYST congeners may change with changes in the environment (Tonk et al, 2005). Maximal cyanotoxin concentrations in a given waterbody, however, largely depend on the concentrations of cyanobacterial biomass – modified by the ratio of toxic to non-toxic strains, currently or previously present.…”

Canine Cyanotoxin Poisonings in the United States (1920s–2012): Review of Suspected and Confirmed Cases from Three Data Sources

“…Differential diagnoses for acute hepatic failure in dogs include poisoning by cyanotoxins like microcystin, nodularin or cylindrospermopsin, cyanotoxins associated with consumption of cycad palms, toxins from poison mushrooms such as amanitin, fungal toxins (e.g., aflatoxin); pharmaceuticals (e.g., acetaminophen and carprofen, or Rimadyl), anticoagulant pesticides, metals (e.g., iron and copper), phosphorous, phenolic compounds, coal tar, and xylitol. Microcystin appears to be a common cyanotoxin affecting dogs in the U.S. [18,24,95,168] and was one focus of the current study. Because identifying causes of acute hepatic failure can be difficult and costly, few cases had confirmatory tests performed for multiple hepatotoxins.…”