In mice exposed to
radiation therapy, D-limonene protected the cells that produce
saliva without diminishing the effects of the radiation therapy. Another
positive discovery made was that the compound can be taken orally and still
reach the salivary glands in humans to produce its effect.
‘Dry mouth is a side effect of radiation therapy, which decreases the capacity of salivary glands to produce enough saliva. A new compound found in citrus oil has been discovered to boost saliva production by protecting saliva-producing-cells.’
The study will be
published online in the Proceedings of the National Academy of Sciences
found in a pair of structures called the submandibular glands situated on both
sides of the chin below the lower jawbone. The cells are instrumental in
keeping the mouth constantly moist. Also present in the glands are the salivary
stem and progenitor cells
which rebuild and restore the capacity to make
does Radiation Affect Salivary Glands?
can kill the saliva-producing cells, as well as,
the salivary stem and progenitor cells.
Retaining the rare
but important stem and progenitor cells is critical but especially tricky
because, following radiation therapy, toxic, highly reactive compounds
called aldehydes are created in the gland
, that muddles up cellular
Head and neck
cancer patients who receive radiation therapy suffer the most. About forty
percent of them develop dry mouth, known clinically as
. The patients struggle to speak and swallow and are more likely
to develop oral pain
dental cavities. Dental cavities can lead to tooth removal in some cases. There
is a chance of recovery in the first years after the therapy, but if saliva
production is impaired, it is usually gone for life.
co-senior author and professor and chair of radiation oncology specializes in
treating head and neck cancer
. She has been hearing about
the struggles of her cancer patients with dry mouth for a decade now.
In an initial
attempt to regenerate salivary stem cells, her lab workers found that the
cells contain high levels of an enzyme called aldehyde dehydrogenase 3A1, or
ALDH3A1 belongs to
the large aldehyde dehydrogenase family of enzymes. These enzymes or proteins
initiate or speed up chemical reactions and can decrease the harmful effects of
troublesome aldehydes. However, ALDH3A1 cannot combat the radiation-unleashed
aldehydes on its own. The enzyme needs to be revved up to be able to tackle the
Le paired up with
Mochly-Rosen who is the George D. Smith Professor in Translational Medicine,
and who had been working on aldehyde dehydrogenases for more than a decade. She
obtained access to a library of 135 traditional Chinese medicine extracts
The extracts have
been used as treatments for various ailments in humans for hundreds of years
and hence were safe to use.
What was more
important was that seven of the 135 extracts boosted ALDH3A1 activity
Now, it was up to graduate student Julie Saiki, to break apart these complex
natural extracts obtained from plants as diverse as tangerine, lotus, an Asian
rhizome known as zhi mu in Chinese among many others to find out what, exactly,
was activating the enzyme.
active ingredient that activated the enzyme, ALDH3A1 was deduced as the
D-limonene stood out from other compounds in the
extracts because it is broken down relatively quickly in the body and is
"generally recognized as safe" as a food additive by the Food and
- Testing if D-limonene can Rev Up ALDH3A1 in Living Cells
- In mouse cells exposed to radiation, D-limonene
reduced aldehyde concentrations in both adult and salivary stem and
- D-limonene was capable of improving the ability
of the cells to recover, repair gland structure and produce saliva even
weeks after radiation exposure.
- Mice that ate D-limonene and were exposed to
radiation produced more saliva than mice that did not receive D-limonene
and were exposed to radiation.
- Did not boost saliva production so high that
mice, or humans, would be drooling.
- Did not increase saliva production in mice that
were not exposed to radiation.
- Did not affect tumor growth or interfere with the
tumor-shrinking effects of the radiation in mice.
- Stopped the expression of messages that trigger
the salivary stem and progenitor cells to self-destruct.
Study - An early clinical trial in a small number of
Four patients who
were having a salivary gland tumor removed were given D-limonene
capsule by mouth for two weeks before the surgery.
researchers found high levels of D-limonene in the removed tissue
proving that the compound taken orally reaches the salivary gland tissue.
D-limonene can thus
be used therapeutically in humans.
The next step is
to start the clinical trial process. "If it works, then this type of drug
would be used safely to prevent dry mouth in patients in the long run and make
it much easier for patients to tolerate the radiation treatment with an
improved quality of life after the treatment," Le said.
Mouth - Xerostomia
Dry mouth occurs
when there is not enough saliva in your mouth.
It is not a rare
occurrence but is present all or most of the time, can be uncomfortable and can
lead to serious health problems.
Symptoms of dry
mouth include a sticky, dry feeling in the mouth
and throat, trouble
chewing, swallowing, tasting, or speaking, cracked lips
, dry and rough
, a burning feeling or
an infection in the mouth.
Dry mouth is
caused due to some medicines, radiation therapy, chemotherapy, and nerve
damage. Other causes could be salivary gland diseases, Sjogren's syndrome
, HIV/AIDS, and diabetes.
Treatment depends on the cause.
- Stanford Medicine. "Compound in citrus oil could reduce dry mouth in head, neck cancer patients". ScienceDaily, (2018).
- Dry Mouth - (https://medlineplus.gov/drymouth.html)