NYU School of Medicine researchers have discovered that dendritic cells in the liver have a protective role against the toxicity of acetaminophen, the widely used over-the-counter pain reliever and fever reducer for adults and children. The study's findings are published in the September issue of the journal Hepatology.
The liver is the organ that plays a central role in transforming and filtering chemicals from the body. High-doses of acetaminophen can cause hepatotoxicity, chemical driven liver damage. In fact, accidental and intentional acetaminophen overdose are the most frequent causes of acute liver failure (ALF) in the United States. Acetaminophen related liver failure by intentional or accidental overdose causes 56,000 emergency room visits, 2,600 hospital visits and 450 deaths annually. As a result, this year the FDA mandated drug manufacturers to start limiting the amount of acetaminophen in combination drug products and is currently exploring adding safer dosing instructions to children's acetaminophen products.
In the new study, researchers found an abundance of dendritic cells in the liver can protect the organ from acetaminophen damage while low levels of dendritic cells in the liver are associated with exacerbated liver damage, liver cell and tissue death, known as centrilobular hepatic necrosis, and acute liver failure from acetaminophen.
"Our research results confirm a central role for dendritic cells and their powerful regulation of acetaminophen's toxicity," said George Miller, MD, senior author of study and assistant professor, Departments of Surgery and Cell Biology at NYU Langone Medical Center. "High levels of dendritic cells have a novel, critical and innate protective role in acetaminophen hepatotoxicity. We now have greater insight into the liver's tolerance of acetaminophen toxicity and dendritic cell regulation of these toxins."
In the study, researchers used acetaminophen-induced hepatic injured mice models to closely examine the protective role of dendritic cells. Dendritic cells are the main antigens in the liver that trigger an immune response and control the liver's tolerance to high doses of invading toxins like acetaminophen. In the experiment all mice were injected with acetaminophen but some mice models were first depleted of dendritic liver cells using a diphtheria toxin while others had their dendritic cell levels bolstered with Flt3L, a protein in the blood previously shown to increase proliferation of dendritic cell levels.
Researchers discovered dendritic cell depletion exacerbates acetaminophen's damage to the liver. The acetaminophen treated mice with depleted dendritic cells had more extensive liver cell and tissue death compared to other mice. Also, these mice died within 48 hours of acetaminophen challenge- whereas death was rare in other mice without dendritic cell depletion. In addition, the study shows dendritic cell expansion successfully diminished the hepatotoxic effects of acetaminophen protecting the liver from damage.
"Understanding the regulatory role of dendritic cells is an important step in the development of immune-therapy for acetaminophen induced liver injury," said Dr. Miller, a member of the NYU Cancer Institute. "Advanced studies are warranted to investigate further the protective role of dendritic cells in humans and their use as a possible new therapeutic target for liver failure prevention in the future."
About NYU Langone Medical Center
NYU Langone Medical Center, a world-class, patient-centered, integrated, academic medical center, is one on the nation's premier centers for excellence in clinical care, biomedical research and medical education. Located in the heart of Manhattan, NYU Langone is composed of three hospitals – Tisch Hospital, its flagship acute care facility; the Rusk Institute of Rehabilitation Medicine, the world's first university-affiliated facility devoted entirely to rehabilitation medicine; and the Hospital for Joint Diseases, one of only five hospitals in the nation dedicated to orthopaedics and rheumatology – plus the NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history. The medical center's tri-fold mission to serve, teach and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education and research. For more information, go to www.NYULMC.org.
Lauren Woods | EurekAlert!
Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel
The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
23.01.2017 | Health and Medicine
23.01.2017 | Physics and Astronomy
23.01.2017 | Process Engineering