Cylindrospermopsin

Cylindrospermopsin (CYN), a cyanotoxin produced by harmful algal blooms, has been reported worldwide; however, there remains limited understanding of its potential risks to surface water quality. In the present study, we critically reviewed available literature regarding the global occurrence, bioaccumulation, and toxicity of CYN in aquatic systems with a particular focus on freshwater. We subsequently developed environmental exposure distributions (EEDs) for CYN in surface waters and performed probabilistic environmental hazard assessments (PEHAs) using guideline values (GVs). PEHAs were performed by geographic region, type of aquatic system, and matrix. CYN occurrence was prevalent in North America, Europe, and Asia/Pacific, with lakes being the most common system. Many global whole water EEDs exceeded guideline values (GV) previously developed for drinking water (e.g., 0.5 μg L-1) and recreational water (e.g., 1 μg L-1). GV exceedances were higher in the Asia/Pacific region, and in rivers and reservoirs. Rivers in the Asia/Pacific region exceeded the lowest drinking water GV 73.2% of the time. However, lack of standardized protocols used for analyses was alarming, which warrants improvement in future studies. In addition, bioaccumulation of CYN has been reported in mollusks, crustaceans, and fish, but such exposure information remains limited. Though several publications have reported aquatic toxicity of CYN, there is limited chronic aquatic toxicity data, especially for higher trophic level organisms. Most aquatic toxicity studies have not employed standardized experimental designs, failed to analytically verify treatment levels, and did not report purity of CYN used for experiments; therefore, existing data are insufficient to derive water quality guidelines. Considering such elevated exceedances of CYN in global surface waters and limited aquatic bioaccumulation and toxicity data, further aquatic monitoring, environmental fate and mechanistic toxicology studies are warranted to robustly assess and manage water quality risks to public health and the environment.

The cyanotoxin cylindrospermopsin (CYN), a toxic metabolite from cyanobacteria, is of particular concern due to its cosmopolitan occurrence, aquatic bioaccumulation, and multi-organ toxicity. CYN is the second most often recorded cyanotoxin worldwide, and cases of human morbidity and animal mortality are associated with ingestion of CYN contaminated water. The toxin poses a great challenge for drinking water treatment plants and public health authorities. CYN, with the major toxicity manifested in the liver, is cytotoxic, genotoxic, immunotoxic, neurotoxic and may be carcinogenic. Adverse effects are also reported for endocrine and developmental processes. We present a comprehensive review of CYN over the past four decades since its first reported poisoning event, highlighting its global occurrence, biosynthesis, toxicology, removal, and monitoring. In addition, current data gaps are identified, and future directions for CYN research are outlined. This review is beneficial for understanding the ins and outs of this environmental pollutant, and for robustly assessing health hazards posed by CYN exposure to humans and other organisms.

Cylindrospermopsin (CYN) has been involved in cases of poisoning in humans following ingestion. Studies have demonstrated that the kidney is the most affected organ. CYN exposure leads to low-molecular-weight proteinuria and increased excretions of the tubular enzymes in mice, suggesting the damage caused by CYN is mainly tubular. However, the mechanism involved in CYN nephrotoxicity remains unknown. Thus, in order to evaluate the effects of CYN exposure (0.1, 0.5 and 1.0 μg/mL) on tubular renal cells LLC-PK1 distinct mechanisms were analyzed by assessing cell death using flow cytometry, albumin uptake by fluorescence analysis, Na+/K+-ATPase activity by a colorimetric method, RT-qPCR of genes related to tubular transport and function as well as internalization of CYN by ELISA. In this study, CYN was found to induce necrosis in all concentrations. CYN also decreased albumin uptake as well as downregulated megalin and dab2 expression, both proteins involved in albumin endocytosis process. Moreover, CYN appears to be internalized by renal tubular cells through a receptor-mediated endocytosis. Finally, the present study demonstrates that CYN is responsible for disrupting tubular cell transport and function in LLC-PK1 cells.

Cylindrospermopsin (CYN) is a cytotoxin, and its documented effects in mammals include damage to several organs. CYN also has hormone-disrupting properties, including estrogenic activity, progesterone production inhibition, and apoptosis induction. While CYN has been reported to exert reproductive toxicity in mice, little is known about its effect on fish reproductive function. Using ex vivo organ culture, we investigated the direct action of CYN on the male reproductive system. Isolated zebrafish testis was exposed to 250, 500, and 1000 µg/L CYN for 24 h and 7 d, followed by histo-morphological analysis. The results demonstrate that exposure to CYN led to a decrease in cell types from all three phases of spermatogenesis in zebrafish testis. There were also significant changes in fshr, lhr, and igf3 transcript levels, as well as testosterone secretion following exposure to CYN. In summary, this study provides novel information on the adverse effects of CYN on testicular spermatogenesis and male reproduction in zebrafish. These results provide a framework for a better understanding of CYN toxicity and the mechanism underlying the adverse action of CYN on male reproduction in fish.