Transcript Avocado - UNM Biology

Avocado
Justin Kaye
Introduction
• I wanted to research the avocado plant
due to the multiple benefits and toxic
effects the plant expresses.
• I will include the following information
about the avocado plant:
- The Origin and common facts about the
avocado.
- Health Benefits that the avocado plant
provides.
Introduction
- Medicinal Benefits.
- Toxic affects due to animal ingestion of the
avocado plant.
- Therapeutic breast cancer affects from the
toxin of avocado plants .
Origins of the Avocado
• Avocado (Persea Americana)
• Locality: Avocado tree is native to Mexico,
Central and northern South America.
• The trees were cultivated by the Incan
civilizations with archeological evidence dating
back to 750 B.C.
• The word “avocado” comes from the Aztec word
ahueketl which means testicle or “fertility fruit” , a
reference to the shape of the fruit.
Health Benefits
• Ounce for ounce avocado provides the
most beta-carotene, potassium,
magnesium, folic acid, thiamin, riboflavin,
niacin, biotin, pantothenic acid, vitamin E
and K, and protein than any other fruit.
• Avocado plants contain oleic acid which is
a monosaturated fat that helps lower
cholesterol.
Health Benefits
• Avocado provides a
good source of
potassium which
helps regulate blood
pressure.
Medicinal Benefits
• Indians in tropical America use the
avocado plant for a variety of medicinal
purposes including:
– The skin is used as an antibiotic and remedy
for dysentery.
– The leaves are chewed as a remedy for
pyorrhea.
– Leaves can be heated and applied to the
forehead to relieve neuralgia.
Medicinal Benefits
– In Cuba the people use the new shoots of the
plant as a cough remedy.
– The seed in powdered form can cure dandruff.
– The exact mechanism of action of how the
plant provides various medicinal benefits is
not yet known.
Avocado is Toxic
• Despite the promising health and
medicinal benefits towards humans, the
consumption of avocado is lethal to many
animals.
• The toxic principle that causes positive
health benefits in humans and negative
effects in animals is known as Persin.
Persin
• Persin is a polyketide which is
similar in structure to the
omega-6 fatty acid, linoleic
acid.
• Researchers have isolated
Persin from specialized cells
found in the avocado plant
called idioblast oil cells.
– Persin appears to be a
defensive compound to
protect avocado from
predators such as insects and
fungi.
Persin
• Researchers have found through experiments that
Persin is responsible for deterring feeding from
insects such as the beet armyworm, spodoptera
exigua ( Rodriguez-Saona et al. 1998).
• Avocado poisoning in animals has been reported
as early as 1942 and Persin was identified as the
toxic component.
Toxic Effects
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High concentrations of Persin are found
in the leaves, bark, seeds, skin, and pits
of the avocado and are the most toxic to
animals.
Toxic Effects include:
–
Horses: Clinical effects occur mainly in mares, and
includes noninfectious mastitis, as well as
occasional gastritis and colic.
Toxic Effects
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Cattle: inflammation of the mammary glands,
decreased milk production.
Rabbits: inflammation of the mammary glands,
decreased milk production, difficulty breathing, fluid
around heart, heart rhythm problems, death.
Goats: inflammation of the mammary glands,
decreased milk production, difficulty breathing, fluid
around heart, heart rhythm problems, and death.
Mice: inflammation of the mammary glands, and
necrosis of the myocardium.
Birds: difficulty breathing, fluid around heart, heart
rhythm problems, death.
Dogs, cats: vomiting, diarrhea.
(ASPCA, 2010)
Persin: Variability in Toxic Effects
• Both the Guatemalen and Mexican
varieties of the avocado are toxic to
animals.
• The most toxic variety due to a higher
concentration of persin is found in the
Guatemalen and Nabal varieties of the
avocado.
• The Mexican Variety is the least toxic
containing the least amount of Persin.
Persin: Variability in Toxic Effects
• It seems plausible from our lectures in class that
the avocado plants that are the most toxic most
likely have the highest predator rate of insects
and fungi living in their region.
• However, this has not yet been studied
scientifically.
• Guatemalan varieties of
avocado have a dark
rough skin.
Persin toxin is identified
• Researchers
conducted an
experiment in which
they isolated Persin
and administered a
single dose of
100mg/kg of Persin to
mice on the 8th day of
lactation (arrow) (Butt
J. Alison et al., 2006).
Persin toxin is identified
• Pup body weight was
measured after the dose
was given and this was
used as an indirect
indicator of mammary
gland function and milk
production.
• Persin treated dams
showed a decrease in
volume of milk production
and pups who were
feeding on Persin treated
dams showed reduced
weight compared with
untreated dams (Butt J.
Alison et al., 2006).
Persin toxin is identified
• Histologically, it was
witnessed that Persin
treated dams had
variable degrees of
necrosis and apoptosis of
alveolar epithelium in the
breast tissue.
• On the right is a
photomicrograph staining
of mammary epithelium
from a normal lactating
dam and dam treated
with single dose of
Persin. There were no
visible effects on other
tissues examined (Butt J.
Alison et al., 2006).
Persin toxicity leads to new
discovery
• Although the toxic compound that causes
animals to become sick after ingesting
avocado has been found, the specific
mechanism of action is still yet to be
known.
• However, researchers were surprised by
the specific effect Persin had on the
mammary tissue of most animals.
Persin toxicity leads to new
discovery
• The specificity of Persin targeting breast
tissue in animals lead researchers to
question how Persin would affect human
breast tissue and breast cancer cells.
Persin Extermination
• Researchers first began by administering
doses of Persin to normal human breast
cell lines in vitro. All of the mammary
epithelial cell lines showed total resistance
to the cytotoxic effects of Persin.
• Next, three human breast cancer cell lines
were examined for their response to
Persin.
Persin Experimentation
• The Estrogen receptor positive
breast cancer cell lines (T-47D,
MCF-7) were significantly
effected by the cytotoxic
effects of Persin.
• However, the Estrogen
receptor negative breast
cancer line (MDA-MB-231)
showed resistance to the
effects of Persin.
• The graph on the right shows
proliferation of Estrogen
positive breast cancer cell
lines were significantly
reduced as compared to the
control group and Estrogen
receptor negative breast
cancer cell line.
Persin Experimentation
• The effects Persin has on Estrogen receptor positive
breast cancer cell lines are due to an induction of a
caspase-dependent apoptosis of the cells signaled by
Persin.
• More research found that the sensitivity of the apoptotic
effects of Persin was associated with expression of the
Bim protein, which acts as an apoptotic activator. This
was found out when Persin-induced apoptosis of breast
cancer cells was inhibited following specific knockdown
expression of Bim expression in the cancer cells.
• This made sense that the Estrogen receptor negative
breast cancer line (MDA-MB-231) showed a resistance
to Persin because of the low levels of Bim expressed by
these types of cells.
• These results provided support to further evaluate Persin
and researchers wanted to find out if Persin could work
together and enhance the benefits of the common breast
cancer drug Tamoxifen.
Tamoxifen
• Tamoxifen is the most common drug used now
to treat breast cancer.
• Most breast cancer cells are Estrogen receptor
positive, which means estrogen can bind to a
receptor protein and promote the proliferation of
more cancer cells.
• Tamoxifen works against the effects of estrogen
on these cells and other cells by competitively
binding to estrogen receptor cells which inhibits
the effects of estrogen.
• Studies have shown that Tamoxifen is only
effective in treating Estrogen receptor positive
breast cancers.
Combining effects of Persin and
Tamoxifen
• Researchers conducted a series of
experiments to find out the effects of a
synergistic approach in combining the anti
cancer agents Persin and Tamoxifen.
• To investigate the interaction between
Persin and Tamoxifen researchers
examined the effects of combined doses
on the long term survival of human breast
cancer cells.
Results
• The diagram on the right
shows the survival of the
Estrogen positive receptor
breast cancer cells (MCF-7
and T-47D) treated with single
and combined doses of Persin
and Tamoxifen(4-OHT).
• Treatment with concentrations
of Persin or Tamoxifen(4-OHT)
resulted in a small change in
survival.
• However, there was a
significant decrease in survival
when the agents were
combined.
Results
• Researchers then wanted to
see if the combined effects
were effective on Estrogen
negative receptor breast
cancer cells (SK-br3).
• The graph on the right
shows Estrogen negative
receptor breast cancer cells
were relatively resistant to
the cytotoxic effects of
Persin and Tamoxifen (4OHT) alone, but there was
a significant induction of
apoptosis when treatment
was combined with Persin.
Mechanism of Action
• From the results shown it has been evident that
human breast cancer cell lines of both Estrogen
positive and negative receptors have an
enhanced response to the cytotoxic effects of
Persin and Tamoxifen when the two agents are
combined.
• Researchers have concluded that this suggests
that Persin has the ability to modulate the
response to antiestrogens by a parallel,
Estrogen receptor pathway of the drug
Tamoxifen.
Mechanism of Action
• More studies found that Persin mediates
its cytotoxic effects in human breast
cancer cells due to the generation of
ceramide, and pro apoptotic synergy is
achieved by addition of Tamoxifen(4-OHT)
to inhibit ceramide glycosylation. The
resulting increase in intracellular ceramide
triggers apoptosis using the Bim
dependent signaling cascade (Butt J.
Alison et al, 2007).
Mechanism of Action
• A picture of the combined parallel mechanism of
Action pathway of Persin and Tamoxifen(4OHT).
• Persin acts as a signal to produce ceramide.
• Tamoxifen inhibits the production of
Glucosylceramide.
• This causes an increase in intracellular
ceramide levels.
• Increased ceramide levels activate the Bim
protein to trigger a cascade event that ends in
celllular apoptosis.
Mechanism of Action
Summary
• After viewing the presentation, one should
have a better understanding of the positive
and negative effects that Persin can have
on humans as well as animals.
• This recent research is very important
towards the treatment of cancer cells and
may be used in cancer drugs in the future
due to its promising synergistic effects with
the breast cancer drug Tamoxifen.
Conclusion
• In conclusion, I feel this research is
important towards finding possible future
cures of cancer in which drugs can provide
effective treatment as well as the lowest
minimum side effects.
• I feel the researchers could try to find out
more about exactly why Persin adversely
effects animal mammary cells as opposed
to human cells.
References
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Butt AJ, Roberts CG, Seawright AA, et al. A novel plant toxin, persin, with in vivo
activity in the mammary gland, induces Bim-dependent apoptosis in human breast
cancer cells. Mol Cancer Ther 2006;5:2300-9.
Butt AJ, Roberts CG, Sutherland RL, et al. Synergistic cytotoxicity between tamoxifen
and the plant toxin persin in human breast cancer cells is dependent on Bim
expression and mediated by modulation of ceramide metabolism. Mol Cancer Ther
2007;6(10):2777-85.
Rodriguez-Saona C, Millar JG, Trumble JT. Isolation, Identification, and Biological
Activity of Isopersin, a new compound from idioblast oil cells. Dept. of Entomology
1998;61:1168-1170.
Knight AP, Walter RG. A guide to plant poisoning of animals in north america.2002.
Morton J. Avocado Fruits of Warm Climates.1987:91-102.
ASPCA Website http://www.aspca.org/pet-care/poison-control/plants/avocado.html
National Cancer Institute Website
http://www.cancer.gov/cancertopics/factsheet/Therapy/tamoxifen
Takano J. Health Benefits of Avocado
http://www.pyroenergen.com/articles07/avocado-health-benefits.htm
Chilean Hass avocados. http://www.chileanavocados.org/chilean-avocados/