Dendritic cells in liver protect against acetaminophen toxicity
September 1, 2011 in Medical research
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."
Provided by
New York University School of Medicine
-
FDA group recommends acetaminophen liver warnings
May 27, 2009 |
not rated yet |
0
-
Questions and answers about pain medicine dangers
Jul 07, 2009 |
not rated yet |
0
-
Medication effective for acute liver failure in early stages of disease
Oct 08, 2009 |
not rated yet |
0
-
Unique pattern of gene expression can indicate acetaminophen overdose
Oct 31, 2007 |
not rated yet |
0
-
Mixing large doses of both acetaminophen painkiller and caffeine may increase risk of liver damage
Sep 26, 2007 |
not rated yet |
0
-
Motion perception revisited: High Phi effect challenges established motion perception assumptions
Apr 23, 2013 |
3 / 5 (2) |
2
-
Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update)
Apr 02, 2013 |
4.5 / 5 (11) |
5
-
The visual system as economist: Neural resource allocation in visual adaptation
Mar 30, 2013 |
5 / 5 (2) |
9
-
Separate lives: Neuronal and organismal lifespans decoupled
Mar 27, 2013 |
4.9 / 5 (8) |
0
-
Sizing things up: The evolutionary neurobiology of scale invariance
Feb 28, 2013 |
4.8 / 5 (10) |
14
-
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013
-
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013
-
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013
-
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013
-
If you became brain-dead, would you want them to pull the plug?
May 17, 2013
-
MRI bill question
May 15, 2013
- More from Physics Forums - Medical Sciences
More news stories
Study reveals new mechanism for estrogen suppression of liver lipid synthesis
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research
May 23, 2013 |
5 / 5 (1) |
0
|
MRI-based measurement helps predict vascular disease in the brain
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research
May 23, 2013 |
not rated yet |
0
Antibiotics: A new understanding of sulfonamide nervous system side effects
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research
May 23, 2013 |
3 / 5 (1) |
0
|
Scientists discover molecule triggers sensation of itch
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research
May 23, 2013 |
5 / 5 (3) |
0
|
Discarded immune cells induce the relocation of stem cells
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research
May 23, 2013 |
5 / 5 (2) |
0
First drug to improve heart failure mortality in over a decade
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
Hormone levels may provide key to understanding psychological disorders in women
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
Heart failure accelerates male 'menopause'
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
Researchers identify first drug targets in childhood genetic tumor disorder
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
Feds fight morning-after pill age ruling in NY
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
Death highest in heart failure patients admitted in January, on Friday, and overnight
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...