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UT on front line of microcystin research

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Every summer, we read news about harmful algal blooms threatening Toledo’s water supply. These blooms, which are a serious problem worldwide, can make the water unfit for all uses, risking the health of humans and animals alike. In the past few decades, the intensity and number of toxic algal blooms, and the associated economic impacts have increased throughout the world.

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Apurva Lad is a PhD student in the Department of Medical Microbiology and Immunology at the University of Toledo College of Medicine.

ABDULSAHIB ALBEHADILI Enlarge

What is an algal bloom? Algal blooms are made up of cyanobacteria, a class of bacteria that obtains energy by photosynthesis. Cyanobacteria were first described as blue-green algae because of the plant-like blue-green color of the algal blooms. Cyanobacteria also feed off of sewage treatment plants, agricultural, and storm water run-offs that contain high amounts of molecules of nitrogen and phosphorus, also important food to these bacteria.

In addition, air and water temperature, and even the mixing of water layers can aid these notorious cyanobacterial blooms.

Specific species of cyanobacteria produce a toxic molecule called microcystin, which is one of the most common cyanobacterial toxins found in the Great Lakes. Cyanobacteria can produce other toxic molecules too, but microcystins are of highest concern.

Microcystin is released when the bacteria die and persist in the water for weeks to months. Microcystin primarily targets the liver but can also affect the gut, brain, kidney, skin, and other body organs.

There are several different ways to be exposed to microcystin, such as drinking or swimming in contaminated water, or by eating food that is contaminated with microcystin.

It is important to note that the World Health Organization guidelines for exposure to liver toxins such as microcystin were developed for normal individuals with healthy livers.

Unfortunately, many people do not have normal healthy livers. In fact, diseases such as diabetes and obesity and factors like stress, fast-food, and additional environmental factors can cause a liver condition called non-alcoholic fatty liver disease. In this condition, the liver accumulates extra fat and slowly loses its ability to function correctly.

As the rates of diabetes and obesity have doubled in the past 20 years, there has been an equally sharp rise in cases of non-alcoholic fatty liver disease. In fact, this disease has now become one of the most common liver disorders affecting millions of Americans. If not detected, non-alcoholic fatty liver disease can lead to a more progressive and severe liver disease, eventually ending in liver failure.

The effect of algal toxins on the livers of individuals with non-alcoholic fatty liver disease has not been studied. Furthermore, there are no tests that can help doctors identify whether these patients have been exposed to cyanotoxins such as microcystin.

Similarly, there are no tests to help healthcare providers to monitor the extent of specific liver damage by exposure to cyanotoxins. Finally, there are no approved treatments for people in this population who have been exposed to additional liver damage from these toxins. These are critical gaps in knowledge which our laboratory at the University of Toledo is beginning to address.

Our first focus is prevention. Here we need to understand how microcystin affects non-alcoholic fatty liver disease. In order to do this, we are performing experiments to understand the effects of microcystin in a non-alcoholic fatty liver disease setting.

This will help us to figure out if the presence of non-alcoholic fatty liver disease increases sensitivity to the toxic effects of microcystin on the liver and other organs. Our research will help to define new guidelines to aid in efforts to prevent microcystin exposure, especially in patients with pre-existing liver disease.

Our second approach focuses on developing tests to accurately measure microcystin exposure in patients. We are developing blood and urine tests that can detect cyanotoxins at very low levels, and we are also looking at new biomarkers which will help us specify if liver damage is because of Non-alcoholic Fatty Liver Disease or caused by microcystin. By this approach, we can help healthcare providers to diagnose and monitor patients who have been exposed to these toxins.

Finally, we are looking closely at several new drugs, some of which were developed at the University of Toledo, to block the toxic effects of microcystins in the liver. This approach is aimed at providing therapies for patients who have already been exposed to these toxins.

By focusing our efforts on these preventative, diagnostic, and therapeutic measures, the University of Toledo College of Medicine, formerly the Medical College of Ohio, is leading the way to safeguarding human health, especially in those patients who may be most vulnerable to negative effects of microcystin.

Apurva Lad is a PhD student in the Department of Medical Microbiology and Immunology at the University of Toledo College of Medicine and Life Sciences Biomedical Science Program, formerly the Medical College of Ohio. She is doing her research in the laboratory of David Kennedy and Steven Haller. For more information, contact Apurva.Lad@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical.

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