Aflatoxin is a deadly fungal toxin produced by a variety of naturally occurring Aspergillus mold species, and are common contaminants in agricultural crops such as corn, peanuts, and tree nuts. Aflatoxin is one of the most potent liver carcinogens known and can lead to hepatic cancer with chronic exposure. Acute exposure to high doses of aflatoxin, or aflatoxicosis, is highly toxic and can cause severe nausea, vomiting, abdominal pain, pulmonary edema, acute liver necrosis, liver failure, and death. This investigation was prompted by many concerns over the potential weaponization of aflatoxin due to its high toxicity, environmental stability, ease of dissemination via air/water/food, the ability to be produced in large quantities, and the need for an effective medical countermeasure for military and civilian personnel.
We have previously reported that CytoSorb® rapidly and effectively adsorbs more than 90% of aflatoxin and the T2 mycotoxin from whole blood in an in vitro recirculation system scaled for human treatment in 1 hour. In the current study, Dr. Karl-Gustav Ruggeberg, PhD and colleagues further investigated if CytoSorb® blood purification could rescue rats administered with a lethal (LD90) intravenous dose of aflatoxin B1. In contrast to inhalation or gastrointestinal exposure, intravenous injection of aflatoxin results in rapid distribution of high levels of toxin throughout the body, making it one of the most difficult models to demonstrate benefit. Blood purification with CytoSorb was initiated either immediately, 30, 90, or 240 minutes after aflatoxin injection, and compared to control animals that underwent the same procedure, but with a sham cartridge instead of CytoSorb.
Key study findings using CytoSorb to treat acute aflatoxin poisoning in rats include:
Rapid 95% reduction of the toxin within 5 minutes of immediate CytoSorb treatment, versus only 37% in the control (p<0.05)
Statistically significant improvement in survival with immediate and delayed CytoSorb treatment within 90 minutes after aflatoxin injection, even after the near complete systemic distribution of the toxin
Immediate: Survival of 60% CytoSorb (n=10) vs 12.5% control (n=8), p<0.025
30 minute delay: Survival of 75% CytoSorb (n=8) vs 0.0% control (n=8), p<0.003
90 minute delay: Survival of 100% CytoSorb (n=11) vs 66% control (n=12), p<0.04
240 minute delay: Survival of 25% CytoSorb (n=8) vs 0.0% control (n=8), p=N.S.
Significantly attenuated aflatoxin-induced weight loss
A notable decrease in gross signs of intoxication including lethargy and hypothermia
Less liver necrosis, inflammation, and hemorrhage
Altered levels of more than 100 circulating proteins including protease/endopeptidase inhibitors, coagulation factors, complement proteins, carbonic anhydrases, and redox enzymes
Dr. Maryann Gruda, PhD, Director of Biology at CytoSorbents and corresponding author stated, "We are pleased to have our work published in this highly cited, peer-reviewed publication. Together, these results underscore the future potential of CytoSorb as a possible countermeasure against acute aflatoxin exposure, and potentially other deadly toxins, to protect our troops and civilians. Furthermore, the identification of a broad spectrum of proteins from key physiologic pathways modulated by CytoSorb treatment may aid future human studies in the treatment of hospital-acquired invasive aspergillosis – a common and deadly fungal infection where aflatoxin contributes to its lethality - and acute liver failure."
Dr. Thomas Golobish, PhD, Senior Director of Polymer Development at CytoSorbents and key investigator added, "The simplicity of CytoSorb treatment belies the sophisticated immunomodulatory effect of the therapy. The broad-spectrum ability of CytoSorb to rapidly reduce aflatoxin and a wide variety of other inflammatory toxins is key to its efficacy in many diseases. We thank the JPEO-CBD for funding this vital research program."
Dr. Phillip Chan, MD, PhD, Chief Executive Officer of CytoSorbents concluded, "This paper represents an outstanding and comprehensive body of research performed by scientists at CytoSorbents that highlights yet another life-or-death application where CytoSorb has benefit. One of the most exciting and unexpected findings of this research is that even a delayed intervention up to 90 minutes following direct injection of aflatoxin into rats, improves survival and reduces liver injury. If this ultimately translates into a broader window of therapeutic intervention in humans, following either accidental or deliberate (e.g. bioterrorism) exposure, it would give victims, whether military or civilian, time to get to definitive care and be treated."
This work was funded by the U.S. Joint Program Executive Office for Chemical and Biological Defense (JPEO-CBD) under contract W911QY-17-C-0007.
CytoSorbents Corporation is a leader in critical care immunotherapy, specializing in blood purification. Its flagship product, CytoSorb® is approved in the European Union with distribution in 58 countries around the world, as an extracorporeal cytokine adsorber designed to reduce the "cytokine storm" or "cytokine release syndrome" that could otherwise cause massive inflammation, organ failure and death in common critical illnesses. These are conditions where the risk of death is extremely high, yet no effective treatments exist. CytoSorb® is also being used during and after cardiac surgery to remove inflammatory mediators that can lead to post-operative complications, including multiple organ failure. CytoSorbents is conducting its pivotal REFRESH 2-AKI trial – a multi-center, randomized controlled, clinical trial intended to support U.S. regulatory approval of CytoSorb for use in a heart-lung machine during complex cardiac surgery to reduce organ injury. The Company has also initiated the company-sponsored U.K. TISORB trial evaluating the removal of ticagrelor in emergency cardiac surgery patients. CytoSorb® has been used in more than 80,000 human treatments to date.
CytoSorbents' purification technologies are based on biocompatible, highly porous polymer beads that can actively remove toxic substances from blood and other bodily fluids by pore capture and surface adsorption. Its technologies have received non-dilutive grant, contract, and other funding of approximately $29 million from DARPA, the U.S. Army, the U.S. Department of Health and Human Services, the National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI), U.S. Special Operations Command (SOCOM), and others. The Company has numerous products under development based upon this unique blood purification technology protected by many issued U.S. and international patents and multiple applications pending, including CytoSorb-XL™, HemoDefend™, VetResQ™, K+ontrol™, ContrastSorb, DrugSorb, and others. For more information, please visit the Company's websites at www.cytosorbents.com and www.cytosorb.com or follow us on Facebook and Twitter.
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