News 20 april 2009
Harvard
Medical Students Rebel Against Pharma-Ties
200 Harvard Medical School STUDENTS are
confronting the administration demanding an end to pharmaceutical industry influence in
the classroom. A front page report in the Business section of the New York Times should
bestir some of Harvard Medical School alumni. 200 Harvard Medical School STUDENTS are
confronting the administration demanding an end to pharmaceutical industry influence in
the classroom. "The students say they worry that pharmaceutical industry scandals in
recent years - including some criminal convictions, billions of dollars in fines, proof of
bias in research and publishing and false marketing claims - have cast a bad light on the
medical profession. And they criticize Harvard as being less vigilant than other leading
medical schools in monitoring potential financial conflicts by faculty members."
Autism is Not Mental Illness: Get
it Out of the DSM
In this month of Autism Awareness, I am
ever so aware of the great disparity for our children on the autism spectrum regarding
their diagnosis and healthcare. It brings to light some major changes that need to take
place in order to not only stop the perpetual, exponentially expanding numbers of children
developing autism, but to provide the already affected children with proper medical care
and treatment.
Agent Orange exposure increases
veterans' risk of aggressive recurrence of prostate cancer
Veterans exposed to Agent Orange are at
increased risk of aggressive recurrence of prostate cancer, researchers report. A study of
1,495 veterans who underwent radical prostatectomy to remove their cancerous prostates
showed that the 206 exposed to Agent Orange had nearly a 50 percent increased risk of
their cancer recurring despite the fact that their cancer seemed relatively nonaggressive
at the time of surgery. And, their cancer came back with a vengeance: the time it took the
prostate specific antigen, or PSA, level to double an indicator of aggressiveness
was eight months versus more than 18 months in non-exposed veterans. "There is
something about the biology of these cancers that are associated with prior Agent Orange
exposure that is causing them to be more aggressive. We need to get the word out,"
says Dr. Martha Terris, chief of urology at the Charlie Norwood VA Medical Center in
Augusta and professor of urology at the Medical College of Georgia School of Medicine.
Mayo Clinic Researchers Formulate
Treatment Combination Lethal To Pancreatic Cancer Cells
A combination of two targeted therapies
packs a powerful punch to kill pancreatic cancer cells in the laboratory, Mayo Clinic
cancer researchers report. With further testing of these drugs that are from classes of
pharmaceuticals already used in patients, the Mayo research may lead to new treatment
opportunities for patients with pancreatic cancer, which is extremely difficult to treat.
Critical turning point can trigger
abrupt climate change
Ice ages are the greatest natural climate
changes in recent geological times. Their rise and fall are caused by slight changes in
the Earth's orbit around the Sun due to the influence of the other planets. But we do not
know the exact relationship between the changes in the Earth's orbit and the changes in
climate. New research from the Niels Bohr Institute indicates that there can be changes in
the CO2 levels in the atmosphere that suddenly reach a critical turning point and with
that trigger the dramatic climate changes. The results are published in the American
journal Paleoceanography.The Earth's climate is essentially contolled by three different
cycles (Milankovitch). All three cycles are caused by the pull of the other planets in the
solar system on the Earth, and one could say that they control the Earth's climate by
causing changes in the Sun's radiation.
1 - The Earth's orbit around the sun is not
completely circular, but slightly elliptical. The orbit is 'elastic' and contracts and
expands in a cycle of 100.000 years. And the closer we are to the Sun, the more solar
radiation and the more heat we receive.
2 - The Earth's axis has a tilt in relation
to the Sun and that is why we have summer and winter. But the tilt is not constant, it
swings between 22 degrees and 24 degrees, and the greater the tilt, the greater the
difference between summer and winter. This cycle takes 40.000 years.
3 - The Earth rotates around on its axis
like a top - this gives day and night. But due to the tilt of the Earth and the elliptical
orbit the direction changes with a cycle of 20.000 years. This results in varation in to
whether the Earth is nearest the Sun during the summer or during the winter.
Solar radiation varies in the two
hemispheres during the summer due to these cycles in the Earth's tilt and the elliptical
orbit and this has profound implications for whether ice caps can build up in the northern
hemisphere, where the largest land areas are.
Human stem cells promote healing of
diabetic ulcers
Treatment of chronic wounds is a continuing
clinical problem and socio-economic burden with diabetic foot ulcers alone costing the NHS
£300 million a year. Scientists in Bristol have found that human foetal stem cells can
effectively be used to treat back leg ischaemic ulcers in a model of type 1 diabetes. The
researchers also found the culture in which the stem cells had been grown mimicked the
wound-healing ability of the cells, suggesting that they could be used as a
"factory" of wound-healing substances. Alternatively, the active ingredients in
the culture, once identified, could be used instead; this would avoid the ethical concerns
of using human foetal stem cells. In humans, diabetic patients with ischaemic foot ulcers
have the worst outcome of all chronic skin wounds, with higher amputation and mortality
rates than patients carrying non-ischaemic ulcers. Topical gels containing single growth
factors have recently been used with some success in non-ischaemic ulcers, but have been
unsuccessful in ischaemic ulcers, which are also resistant to other conventional
treatment. Ischaemia results when the blood supply to a tissue is greatly reduced or
stopped - this can occur in diabetes since it can also cause impaired blood flow in
patients. The healing activity of stem cells is recognised for their ability to separate
into the various component cells of injured tissues, as well as to discharge growth
factors that may encourage the formation of new blood vessels in the patient. Paolo
Madeddu, Professor of Experimental Cardiovascluar Medicine and colleagues at the Bristol
Heart Institute, previously used stem cells in models of back leg ischaemia, showing that
foetal stem cells could be more therapeutically effective than adult stem cells. Foetal
stem cells possess a better ability to multiply and to graft onto host tissue, and to
separate into other cell types to replace those in the damaged tissue. The group led by
Bristol University's Professor Madeddu have found that foetal stem cells accelerate the
closure of ischaemic diabetic ulcers, while stem cells from blood of adult donors are
ineffective. Professor Madeddu, commenting on the research, said: "This is the first
study to demonstrate the healing capacity of local therapy with CD133+ stem cells in a
model of diabetic ischaemic foot ulcer. The foetus-derived cells would be difficult to
obtain for therapeutic applications. However, the finding that conditioned culture is also
effective in stimulating wound healing may have important implications for the cure of the
ischaemic complications of diabetes.
New study finds continued
abstinence is key to increased survival from alcohol-related liver disease
However, the downside is that up a quarter
of people with alcohol-related cirrhosis die before they get the chance to stop drinking.
Alcohol-related cirrhosis develops silently but usually presents with an episode of
internal bleeding or jaundice - which is often fatal. The study, led by Dr Nick Sheron,
senior lecturer at the University of Southampton and consultant hepatologist at
Southampton General Hospital, found that abstinence from alcohol is the key factor in
long-term prognosis, even with relatively severe alcohol-related cirrhosis of the liver.
The study appears in this month's Addiction journal. The aim was to determine the effect
of pathological severity of cirrhosis on survival in patients with alcohol-related
cirrhosis. Liver biopsies from 100 patients were scored for the Laennec score of severity
of cirrhosis between 1 January 1995 and 31 December 2000, and medical notes were reviewed
to determine various clinical factors including drinking status. Using up-to-date
mortality data from the National Health Service Strategic Tracing Service, Dr Sheron found
that drinking status was the most important factor determining long-term survival in
alcohol-related cirrhosis of the liver. He found that the degree of cirrhosis on biopsy
had less impact on survival. Abstinence from alcohol at one month after diagnosis of
cirrhosis was the more important factor determining survival with a seven year survival of
72 per cent for the abstinent patients against 44 per cent for the patients continuing to
drink.
Study identifies genes that protect
against aging
Scientists at the University of Liverpool
have developed a new method to help researchers identify genes that can help protect the
body during the ageing process. The team developed a method of analysing genes in multiple
ageing tissue types in both animals and humans. The analysis, which included more than
five million gene measurements, highlighted the mechanisms used by the body to protect
against cellular changes with age that can result in conditions such as muscle
degeneration and cognitive ageing. The new method could help further understanding into
anti-ageing interventions by identifying genes that indicate biological changes as a
result of ageing. Research has suggested that some genes respond to age-related conditions
by increasing key protein levels, allowing the body to manage the ageing process more
effectively. Dr Joao Pedro Magalhaes, from the University's School of Biological Sciences,
explains: "We developed a new algorithm to analyse microarray data of genes from
different species, and combined data from multiple studies to obtain a picture of how
genes respond to ageing in a whole organism. This method is similar to the way scientists
study the molecular characteristics of cancer, but it is the first time it has been used
to research ageing.
New insight into Rett syndrome
severity
A research collaboration between Australia
and Israel has identified a genetic variation that influences the severity of symptoms in
Rett syndrome. The finding is published in the latest edition of the international journal
Neurology. Dr Helen Leonard, who heads the Australian Rett Syndrome Study at the Telethon
Institute for Child Health Research, said the finding was exciting in that it identifies a
potential new target for treatment of the debilitating neurological disorder. "We
know that there is a wide range in the onset and severity of symptoms in patients with
Rett syndrome but it has been difficult to give families a firm idea of how the disorder
would progress," Dr Leonard said. "This information is potentially helpful in
predicting the clinical progression, but importantly, gives us another area to explore for
potential therapies." In the study, clinical information and DNA samples were
gathered from 125 patients from the Australian Rett Syndrome Database and an Israeli
cohort coordinated by Dr Bruria Ben Zeev at the Safra Pediatric Hospital, Sheba Medical
Centre, Sackler School of Medicine, Tel Aviv. The genetic testing was undertaken by
Professor John Christodoulou, from the NSW Centre for Rett Syndrome Research at the
Children's Hospital at Westmead in Sydney and Dr Eva Gak from the Sagol Neuroscience
Center at the Sheba Medical Centre. Professor Christodoulou said while it has been
established that Rett syndrome is caused by mutations in the MECP2 gene, these new
findings have established a correlation between the severity of clinical symptoms and a
common brain-derived neurotrophic factor (BDNF) polymorphism. "Those patients with
the normal BDNF genetic variant had less severe symptoms, with later onset and frequency
of seizures," Dr Christodoulou said.
Vegan Buddhist nuns have same bone
density as non-vegetarians
A study comparing the bone health of 105
post-menopausal vegan Buddhist nuns and 105 non-vegetarian women, matched in every other
physical respect, has produced a surprising result. Their bone density was identical. The
study was led by Professor Tuan Nguyen from Sydneys Garvan Institute of Medical
Research. He collaborated with Dr Ho-Pham Thuc Lan from the Pham Ngoc Thach Medical
University in Ho Chi Minh City,Vietnam. Their findings are now published online in
Osteoporosis International. "For the 5% of people in Western countries who choose to
be vegetarians, this is very good news," said Professor Nguyen. "Even vegans,
who eat only plant-based foods, appear to have bones as healthy as everyone else."
"Bone health in vegetarians, particularly vegans, has been a concern for some time,
because as a group they tend to have a lower protein and calcium intake than the
population at large."
Breakfast choices impact hunger and
calorie consumption throughout day
New studies presented this week at
Experimental Biology 2009 enhance the growing body of evidence supporting the nutritional
benefits of eggs. Research presented at the meeting demonstrates that choosing eggs for
breakfast can help adults manage hunger while reducing calorie consumption throughout the
day. Additional research shows that teens who choose a protein-rich breakfast are less
hungry and eat fewer calories at lunch.
USC researchers develop new drug to
target tumor cells and blood vessels
Researchers at the University of Southern
California have identified a new drug compound that appears to target tumor cells and
surrounding blood vessels without the negative side effects typically associated with
Cox-2 inhibitors. The compound 2.5-dimethyl-celecoxib (DMC) appears to have a strong
anti-tumor effect while also attacking the vasculature that provides the blood supply
necessary for tumor growth, according to data presented at the AACR 100th Annual Meeting
2009. The findings were presented at a 1 p.m. news conference on Sunday, April 19.
"If left behind, the blood vessels within the tumor will help the tumor cells to
survive and re-grow," says Florence M. Hofman, Ph.D., professor of pathology at the
Keck School of Medicine of USC. "We believe that DMC will be particularly useful for
treating brain tumors such as gliomas, which are highly vascular. It also appears very
promising for long-term treatment because it does not have the negative cardiovascular
effects associated with Cox-2 inhibitors." Cox-2 inhibitors are most commonly used as
anti-inflammatory drugs and have been shown to be effective in treating certain kinds of
cancer. However, long-term use has also been associated with increased risk of heart
attack and stroke, Hofman explains. DMC, however, retains anti-tumor activity without
inhibition of Cox-2 and the associated increased risk of cardiovascular complications.
Hofman and colleagues from the Keck School of Medicine tested the effectiveness of the DMC
compound by isolating endothelial cellsthe cells that line the interior surface of
blood vesselsfrom human nonmalignant brain and glioma tissues and treating them with
DMC.
Autopilot Guides Proteins in Brain
Proteins go everywhere in the cell and do
all sorts of work, but a fundamental question has eluded biologists: How do the proteins
know where to go? "Theres no little man sitting there, putting the protein in
the right place," said Don Arnold, a molecular and computational biologist at USC
College. "Proteins have to have in them encoded information that tells them where to
go in the cell." In a study appearing online this week in Nature Neuroscience, Arnold
and collaborators solve the mystery for key proteins in the brain. Neurons have separate
structures for receiving signals (dendrites) and for sending them (axons). The electrical
properties of each depend on different proteins. But the proteins travel in bubbles, or
vesicles, powered by motors known as kinesins that travel along tiny molecular paths.
Even though the paths point to both axons
and dendrites, dendritic proteins end up in dendrites, and axonal proteins go to the
axons. How? Arnolds group discovered a crude but effective sorting mechanism. At
first, kinesins blindly carry both types of proteins towards the axon. However, dendritic
proteins enable the vesicles transporting them to bind to a second motor, known as myosin,
that literally walks them back into the dendrite. This filter ensures that only axonal
proteins make it into the axon. The others are caught by the second motor and diverted to
the dendrite. "This mechanism fishes these things out of the axon," Arnold said.
Brain metastases hijack
neuron-supporting cells to resist chemotherapy
Cancer that spreads to other organs finds a
particularly inviting hideout in the brain, where these metastases are usually far harder
to treat than they are in other locations. Two researchers from The University of Texas M.
D. Anderson Cancer Center discussed ways to more successfully target these tumors in their
"sanctuary" at the American Association for Cancer Research 100th Annual Meeting
2009 in Denver. Professor of Cancer Biology Isaiah J. Fidler, D.V.M., Ph.D., presented a
novel theory about why brain metastases are resistant to chemotherapy. "Astrocytes
are spider-like cells that normally play the important role of providing oxygen and
nutrients to neurons, and protecting neurons from naturally occurring toxins," Fidler
said. "We show that brain metastases subvert astrocytes, tricking them into
protecting the tumors, and that this is the important factor in resistance to
chemotherapy." Professor and Chair of Neurosurgery Raymond Sawaya, M.D., reviewed
when and how to conduct surgery to remove metastatic tumors, including evidence that
removing a tumor piecemeal raises the risk of cancer irretrievably spreading to the spinal
fluid. Fidler and Sawaya were among five speakers at "Invading the Sanctuary: New
approaches to Brain Metastasis." Metastatic cancer causes the vast majority of cancer
deaths. There are more than 100,000 new cases of metastatic brain cancer each year. By
comparison, primary malignant brain tumors account for about 17,000 new cases annually.
Not all cancers spread to the brain. Sawaya lists lung, breast, melanoma, kidney and colon
cancer as the most common. "It's common for us to operate on patients who no longer
have known disease except for the metastasis in the brain," Sawaya said. Such
patients have a better prognosis than those with heavier tumor burden elsewhere.
An herbal extract inhibits the
development of pancreatic cancer
An herb recently found to kill pancreatic
cancer cells also appears to inhibit development of pancreatic cancer as a result of its
anti-inflammatory properties, according to researchers from the Kimmel Cancer Center at
Jefferson. The data were presented at the AACR 100th Annual Meeting 2009 in Denver.
(Abstract 494) Thymoquinone, the major constituent of the oil extract from a Middle
Eastern herbal seed called Nigella sativa, exhibited anti-inflammatory properties that
reduced the release of inflammatory mediators in pancreatic cancer cells, according to
Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at the Jefferson Medical College
of Thomas Jefferson University and a member of the Jefferson Pancreatic, Biliary &
Related Cancers Center. Nigella sativa seeds and oil are used in traditional medicine by
many Middle Eastern and Asian countries. It helps treat a broad array of diseases,
including some immune and inflammatory disorders, Dr. Arafat said. Previous studies have
also shown it to have anti-cancer effects on prostate and colon cancers. Based upon their
previously published findings that thymoquinone inhibits histone deacetylases (HDACs), Dr.
Arafat and her colleagues compared the anti-inflammatory properties of thymoquinone and
trichostatin A, an HDAC inhibitor that has previously shown to ameliorate
inflammation-associated cancers. The researchers used pancreatic ductal adenocarcinoma
(PDA) cells, some of which were pretreated with the cytokine TNF-alpha to induce
inflammation. Thymoquinone almost completely abolished the expression of several
inflammatory cytokines, including TNF-alpha, interleukin-1beta, interleukin-8, Cox-2 and
MCP-1, an effect that was more superior to the effect of trichostatin A. The herb
also inhibited the activation and synthesis of NF-kappaB, a transcription factor that has
been implicated in inflammation-associated cancer. Activation of NF-kappaB has been
observed in pancreatic cancer and may be a factor in pancreatic cancer's resistance to
chemotherapeutic agents. When animal models of pancreatic cancer were treated with
thymoquinone, 67 percent of the tumors were significantly shrunken, and the levels of
proinflammatory cytokines in the tumors were significantly reduced.
LSUHSC research shows fish oil
protects against diseases like Parkinson's
Dr. Nicolas Bazan, Director of the
Neuroscience Center of Excellence, Boyd Professor, and Ernest C. and Yvette C. Villere
Chair of Retinal Degenerative Diseases Research at LSU Health Sciences Center New Orleans,
will present new research findings showing that an omega three fatty acid in the diet
protects brain cells by preventing the misfolding of a protein resulting from a gene
mutation in neurodegenerative diseases like Parkinson's and Huntington's. He will present
these findings for the first time on Sunday, April 19, 2009 at 10:30 a.m. at the Ernest N.
Morial Convention Center, Nouvelle C Room, at the American Society for Nutrition,
Experimental Biology 2009 Annual Meeting. With funding from the National Eye Institute of
the National Institutes of Health, Dr. Bazan and his colleagues developed a cell model
with a mutation of the Ataxin-1 gene. The defective Ataxin-1 gene induces the misfolding
of the protein produced by the gene. These misshapened proteins cannot be properly
processed by the cell machinery, resulting in tangled clumps of toxic protein that
eventually kill the cell. Spinocerebellar Ataxia, a disabling disorder that affects
speech, eye movement, and hand coordination at early ages of life, is one disorder
resulting from the Ataxin-1 misfolding defect. The research team led by Dr. Bazan found
that the omega three fatty acid, docosahexaenoic acid (DHA), protects cells from this
defect. Dr. Bazan's laboratory discovered earlier that neuroprotectin D1 (NPD1), a
naturally-occurring molecule in the human brain that is derived from DHA also promotes
brain cell survival. In this system NPD1 is capable of rescue the dying cells with the
pathological type of Ataxin-1, keeping their integrity intact. "These experiments
provide proof of principle that neuroprotectin D1 can be applied therapeutically to combat
various neurodegenerative diseases," says Dr. Bazan. "Furthermore, this study
provides the basis of new therapeutic approaches to manipulate retinal pigment epithelial
cells to be used as a source of NPD1 to treat patients with disorders characterized by
this mutation like Parkinson's, Retinitis Pigmentosa and some forms of Alzheimer's
Disease."
Clouds - Lighter than air but laden
with lead
By sampling clouds -- and making their own
-- researchers have shown for the first time a direct relation between lead in the sky and
the formation of ice crystals that foster clouds. The results suggest that lead generated
by human activities causes clouds to form at warmer temperatures and with less water. This
could alter the pattern of both rain and snow in a warmer world. The lead-laden clouds
come with a silver lining, however. Under some conditions, these clouds let more of the
earth's heat waft back into space, cooling the world slightly. Atmospheric lead primarily
comes from human sources such as coal. The international team of researchers reported
their results in the May issue of Nature Geoscience. The collaboration included
researchers from institutions in the United States, Switzerland and Germany. "We know
that the vast majority of lead in the atmosphere comes from man-made sources," said
atmospheric chemist Dan Cziczo of the Department of Energy's Pacific Northwest National
Laboratory and study author. "And now we show that the lead is changing the
properties of clouds and therefore the balance of the sun's energy that affects our
atmosphere."
Urine test may determine if a
smoker is at risk for lung cancer
Researchers may have uncovered why lung
cancer afflicts some smokers and not others, according to data presented at the American
Association for Cancer Research 100th Annual Meeting 2009. "A history of smoking has
always been thought of as a predictor of lung cancer, but it is actually not very
accurate," said Jian-Min Yuan, Ph.D., M.D., associate professor of public health at
the University of Minnesota. "Smoking absolutely increases your risk, but why it does
so in some people but not others is a big question." Yuan and colleagues hypothesized
that the presence of the metabolite NNAL in a patient's urine might predict risk of lung
cancer. This metabolite has been shown to induce lung cancer in laboratory animals, but
the effect in humans had not yet been studied. Researchers collected data from 18,244 men
enrolled in the Shanghai Cohort Study and 63,257 men and women from the Singapore Chinese
Health Study. In addition to in-person interviews to assess levels of cigarette smoking,
dietary and other lifestyle factors, researchers collected blood and urine samples from
more than 50,000 patients. To evaluate the impact of NNAL, researchers identified 246
current smokers who later developed lung cancer and 245 smokers who did not develop lung
cancer during the 10-year period following initial interview and collection of urine
samples. Levels of NNAL in the urine were divided into three groups. Compared to those
with the lowest levels, patients with a mid-range level of NNAL had a 43 percent increased
risk of lung cancer, while those at the highest level had a more than two-fold increased
risk of lung cancer after taking into account the effect of number of cigarettes per day,
number of years of smoking, and urinary levels of cotinine on lung cancer risk. Levels of
nicotine in the urine were also calculated. Those with the highest levels of nicotine and
NNAL had an 8.5-fold increase in the risk of lung cancer compared with smokers who had the
lowest levels after accounting for smoking history. "Smoking leads to lung
cancer, but there are about 60 possible carcinogens in tobacco smoke, and the more
accurately we can identify the culprit, the better we will become at predicting
risk," said Yuan.
Is metabolic character different
between men and women with gallstone disease?
There are a cluster of metabolic syndrome,
that include obesity, high level of fasting plasma glucose, hypertriglyceridemia and
hypertension, which is closely associated with the increased morbidity and mortality
caused by several of the most common diseases including diabetes, hypertension,
cardiovascular diseases, cancer and gallstone disease. However, there are regional and
ethic variables in incidence and metabolic risk factors of gallstone disease. No study
explores it in china has been reported. A research article to be published on April 21,
2009 in the World Journal of Gastroenterology addresses this question. The research team
led by Professor Tang from Center of Infectious Diseases, Division of Molecular Biology of
Infectious Diseases, National Key Laboratory of Biotherapy (Sichuan University), West
China Hospital of Sichuan University carried out a study in a check-up unit in a
university hospital in Chengdu city to study the incidence and metabolic risk factor of
gallstone disease. As various researches indicated old age and female sex are susceptible
to gallstone disease, the article investigate the relationship of metabolic disorders and
gallstone disease. The prevalence of gallstone disease among the study subjects was 10.7%
. The reported prevalence of gallstone disease is approximately 3.6% in Japan and 4.3-5.0%
in Taiwan. The present study, in accordance with reports from western countries and other
regions of Asia, showed that an older age, which may lead to exposure to many other risk
factors, and female sex, which may have increasing risk of biliary cholesterol secretion
causing cholesterol super saturation of bile by pregnancy and estrogen, are significant
risk factors for gallstone disease. The present analyses showed a positive association
between DM and gallstone disease in men but not in women and hypertriglyceridemia or
obesity only showed a positive association with gallstone disease in women. There were
disparate findings about DM, hypertriglyceridemia and obesity in different sexes with
gallstone. These results demonstrate men have different metabolic character from women in
gallstone disease patients, which may provide more information for investigating the true
pathological mechanism of gallstone disease.
What is the effect of tea
polyphenols on hepatic drug metabolizing enzymes?
Paracetamol is one of the most widely used,
studied, and arguably the most notorious hepatotoxic drugs, which is safe at therapeutic
doses but causes liver failure when overdosed. When administered at normal doses,
paracetamol is metabolized extensively by conjugation with sulphate and glucuronic acid.
Exposure to high doses of paracetamol results in increased levels of
N-acetyl-p-benzo-quinoneimine (NAPQI), a highly electrophilic metabolite that is
considered to be responsible for triggering the ensuing liver damage. The research, lead
by Dr. Sun and his colleagues in Dalian Medical University, has recently been published on
April 21,2009 in World Journal of Gastroenterology, investigated the effect of tea
polyphenols (TPs) on paracetamol-induced hepatotoxicity. TPs are a large and diverse class
of compounds extracted from tea. Recent studies indicate that TPs prevent from oxidative
stress-related diseases including cancer, cardiovascular diseases, degenerative diseases
and other bioactive properties. In recent years there has been a mounting interest in
understanding the metabolic benefits of TPs. Liver is the main organ responsible for the
metabolism of TPs. And some works have been done in the field of TPs modulated or
interacted with drug metabolizing enzymes. However, until now, no one could give a clear
explanation about this. Cytochrome P450 (CYP450) enzymes play a pivotal role not only in
the metabolism of xenobiotics, and both induction and suppression of several CYP450s may
lead to the cellular oxidative stress and tissue injury in response to xenobiotics. Early
investigations identified the important roles of CYP2E1, CYP1A2 and intracellular GSH in
paracetamol induced hepatotoxicity. But the effect of TPs on paracetamol-induced
hepatotoxicity remain unclear. This research gave a clear explanation of TPs' effect on
hepatic CYP450 along with CYP2E1 and CYP1A2 expression at both protein and mRNA levels.
The results showed that the contents of hepatic CYP450 and CYPb5 were dose-dependently
decreased by TPs. Also, TPs reduced CYP2E1 and CYP1A2 expression at both protein and mRNA
levels dose dependently, indicating that TPs possessed potential hepatoprotective
properties and this effect was closely related with their suppression on CYP450
expression. These results provided new information of TPs about their metabolism and the
effect of TPs on hepatic drug metabolizing enzyme. This will be important in developing
clinically safe and efficient medications related to TPs.