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					Avocado

 Name 1
              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
•   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
–   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 (4-
  OHT) 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(4-
  OHT).
• 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
•   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/

				
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