microcystin and Toxemia

Microcystins are among the most commonly detected toxins associated with cyanobacteria blooms worldwide. Two episodes of intravenous microcystin exposures occurred among kidney dialysis patients during 1996 and 2001. Analysis of serum samples collected during these episodes suggests that microcystins are detectable as free and bound forms in human serum. Our goal was to characterize the biochemical evidence for human exposure to microcystins, to identify uncertainties associated with interpretation of these observed results, and to identify research needs. We analyzed serum samples using enzyme-linked immunosorbent assay (ELISA) methods to detect free microcystins, and gas chromatography/mass spectrometry (GC/MS) to detect 2-methyl-3-methoxy-4-phenylbutyric acid (MMPB). MMPB is derived from both free and protein-bound microcystins by chemical oxidation, and it appears to represent total microcystins present in serum. We found evidence of free microcystins in patient serum for more than 50 days after the last documented exposure. Serum concentrations of free microcystins were consistently lower than MMPB quantification of total microcystins: free microcystins as measured by ELISA were only 8-51% of total microcystin concentrations as detected by the GC/MS method. After intravenous exposure episodes, we found evidence of microcystins in human serum in free and protein-bound forms, though the nature of the protein-bound forms is uncertain. Free microcystins appear to be a small but variable subset of total microcystins present in human serum. Research is needed to elucidate the human toxicokinetics of microcystins, in part to determine how observed serum concentrations can be used to estimate previous microcystin exposure.

Topics: Bacterial Toxins; Brazil; Environmental Exposure; Humans; Microcystins; Renal Dialysis; Toxemia

In November 2001, a cyanobacterial bloom dominated by Microcystis and Anabaena occurred in the Funil Reservoir and the Guandu River, both of which supply drinking water to Rio de Janeiro, Brazil. Using ELISA, microcystins were detected at a concentration of 0.4 microg/L in the drinking water, whereas a concentration of 0.32 microg/L was detected in activated carbon column-treated water for use at the renal dialysis center of Clementino Fraga Filho Hospital (HUCFF) at the Federal University of Rio de Janeiro. A total of 44 hemodialysis patients who received care at this center were believed to be exposed. Initial ELISA analyses confirmed the presence of serum microcystin concentrations > or = 0.16 ng/mL in 90% of serum samples collected from these patients. Twelve patients were selected for continued monitoring over the following 2-month period. Serum microcystin concentrations ranged from < 0.16 to 0.96 ng/mL during the 57 days after documented exposure. ELISA-positive samples were found throughout the monitoring period, with the highest values detected 1 month after initial exposure. ESI LC/MS analyses indicated microcystins in the serum; however, MS/MS fragmentation patterns typical of microcystins were not identified. LC/MS analyses of MMPB for control serum spiked with MCYST-LR. and patient sera revealed a peak at retention time of 8.4 min and a mass of 207 m/z. These peaks are equivalent to the peak observed in the MMPB standard analysis. Taken together ELISA, LC/MS, and MMPB results indicate that these renal dialysis patients were exposed to microcystins. This documents another incident of human microcystin exposure during hemodialysis treatment.

Topics: Bacterial Toxins; Brazil; Environmental Exposure; Enzyme-Linked Immunosorbent Assay; Hemodialysis Units, Hospital; Humans; Microcystins; Microcystis; Peptides, Cyclic; Renal Dialysis; Renal Insufficiency; Toxemia; Water Microbiology