Detoxification Flashcards
What are factors for an increased risk in breast cancer
Xenoestrogens Pollutants Xenobiotics Menopause Stress
How is menopause a risk factor for Breast cancer
spikes estrogen relative to progesterone
excessive stimulation through estrogen receptor
How is stress a risk factor for Breast Cancer
Emotions: more cause most damage Physical and surgical- less often Decrease in melatonin Decrease thyroid Cortisol and Dhea out of balance
How does the tumor contribute to breast cancer
tumor becomes like ovary- produces estrogen- and is primarily the source of inflammation
How is the breast tumor a source of inflammation
as its forming need a good source of glucose
over stimulates the insulin receptors leading to insulin resistance
LH/FSH increase-> PCOS-> testosterone-> estradiol
How does estrogen metabolism become a cancer risk
most estrogen hormones in body are estrosulfate
Key Enzymes: CYP1B1- in liver, kidney and other tissue
CYP1A1: both enzymes move estrogen through pathways
4-OH-E1(E2) with COMT-Methylation of 2-A-4-OH-E1(E2) coverts estrogen or estrodial- is bad but not terrible, if patient methylate well will clear them-
If not methylating well, above reaction will down regulate and lead to cancer
How does estrogen metabolism and pollutant lead to cancer
If making too many estrogens with exposure to pollutants-> induce enzymes that will make bad estrogen and cause DNA formation which leads to DNA damage which results in cacner
What factors contribute to DENA formation, damage and ultimately cancer
Trans Fats- more easily oxide estrogen
Heavy metals: mercury, arsenic: oxidize estrogen
What testing is available for Estrogen
Serum and Plasm
Urine( liquid and dry)
Saliva
What is significant about Estrogen vs Estradiol in terms of metabolism and cancer risk
Harmful if metabolized in the wrong way
Progesterone is natural anti-estrogen
Higher levels of estrogen can have higher levels of catechol of estrogen
What is a common Urinary profile in breast cancer patients
- increased estradiol and estrone
- increased 4-OH-E1 and 4-OH-E2
- decreased ratio of 4-MeO-E1/r-OH-E1
- decreased pregnanediol
- Increased ratio of pregnane/pregnene
- Decreased testosterone and dHT
- Increased EPI testosterone
- Decreased DHEA
Increased diurnal cortisol flat
What are lifestyle changes that reduce risk of breast cancer
Lots of organic veggies- crucious veggies- improve estrogen metabolism
avoid pollutants
Exercise
Get adequate sleep
If hormone deficient- take necessary hormones
DIM- indole-3-carbionol or diindolymethane
omega 3 FA
green algae
Whats the pathway for Estrogen metabolism
E1-SO4-> sulfatase->E1->(17B-HSD-Type1)-E2
Conversely: E2-> (17B-HSD2)->(Sulfotransferase)->E1- SO4
What happens when E1-SO4 is converted to E1
depends on the SNP for processing. If CYP1B1 then issues occur, if CYP1A1 more normal and safer outcome
How does CYP1B1 affect estrogen metabolism in the body
E1->( CYp1B1)-becomes 4-OH-E1(E2) which if appropriate methylation will become metabolites: 2 and 4 MeO-E1(E2)
If not methylating well will become 4-Quinone-E1(E2) and if appropriate GST-GSH conjugation of 2 and 4 quinone E1(E2) will become metabolites- if not will produce DNA adduct formation-> DNA damage mutation-> cancer
How does CYP1A1 affect estrogen metabolism
E1 with CYP1A1-> either 2 OH-E1(E2) or 16-OH-E1. Would like to become 16 as it is metabolized appropriately becoming E3 and binds to protein and no affect on the body. If an issue with CYP1A1 and ability to detox- 2-OH-E1(E2) -> 2-Quinonine-E1(E2)- DNA adduct formation and DNA repair
How is cortisol a factor for Breast Cancer patients
Normal profile: cortisol high in am and low at night
Breast cancer patients- flat line diurnal cortisol and high at night
What key hormones make up the matrix for Breast cancer- estrogen matrix
Testosterone Estrogen Progesterone Cortisol DHEA
Where is estrogen found
produced in ovaries and metabolized in liver
What are benefits of estrogen
metabolism functions correctly vessel and skin increase bone formation increase hepatic production of binding protein increase HDL Decrease LDL Increase cortisol: SHBG Increase Cholesterol in bile Promote lung function
What are 2 key estrogen metabolites
2-Hydroyestrone( 2-OHE1)- inhibit cancer growth- implies balanced metabolism: via reasonable intake of veggies and flaxseed
16-a-hydroxyestrone( 16-a-OHE1)- encourages tumor development- bad estrogen- lupus, breast cancer, levels can rise in response to obesity and alcohol, genetics play a role, is modifiable by measuring estrogen
What is important about 2:16 alpha-Hydroxyestrone ratio
Higher ration less risk for estrogen related cancers
Serum great than .4 is considered to be beneficial
What are mechanisms of heavy metal toxicity
metals generate many of deletions effects through the formation of free radicals, resulting in DNA damage, lipid peroxiding depletion of protein sulfydrase
are everywhere- appear mediated through mitochondrial damage from glutathione depletion
why be concerned about heavy metal toxicity
toxic to all living creature everywhere in environment increase in health damage if not removed may take years for sx to appear causes many diseases and blocks healing mercury is usually hidden as the cause
What systems are affected by mercury
nervous, emotions, reproduction, heart, kidneys, hormones, sexual preference, vision, GI, immune, children/fetus
What has WHO stated about mercury?
mercury is toxic to human health, posing a particular threat to development of child
exists in various forms: elemental, inorganic and organic
No threshold below with some adverse affects do not occur( lowest levels produced adverse affects)
Where is mercury stored?
brain, thyroid, liver and adrenals
What are sources of mercury
amalgams-#1 source fish and other food vaccine thermometer flurescant bulb thermostat barometer light up sport shoes cosmetic disinfectant skin cream tattoo-red dye paint blood pressure gauge button cell batteries
1 mcg or mercury is how many atoms of mercury
1 mcg of mercury= 43,000,000,000 atoms of mercury
1 Large amalgram= 1,000,000mcg of Hg
Mercury is double edged sword of attack
Direct: mercury attaches to protein or enzyme with a sulfhydryl group destroying function
Indirect: weaken immune system while depleting body of glutathione and sand selenium
Can mercury be detoxified?
NO!!
must be taken out physical
2 glutathione molecules los for every atom of mercury
How does selenium affect mercury
Binds to it!
mercury binds to selenium forming mercury selenides thus reducing mercury damaging cytotoxicity
selenium availability for many other important enzyme reaction is reduce
How does mercury relate to CVD
patients with amalgam bearing had higher BP and greater amount of chest pain, tachycardia, anemia, fatigue, tiring easily, and being tired in the morning
Atherosclerosis- activates an enzyme called phospholipase D in cells that line arteries causing release of phophatidic acids damaging endothelia cells-
Treatment: chelators
What are some emotions that associated with mercury toxicity
Indecision, low self-esteem, shyness, overwhelm, lack of joy, hopelessness, lack of motivation, depression, fearfulness, anxiety, panic, impeding doom, irritability, aggression, inappropriate anger, rage
How does mercury disrupt the brain
lack of focus brain fog forgetfulness/memory dementia Journal of Neurochemistry- mercury induces cell cytotoxicity and oxidative stress and increase in b-amelyoid secretion and Tau phosphorylation in Neuroblastoma cells; mercury may play a role in pathophysiological mechanism of AD
How does mercury affect the nervous system
frequent chronic headache tremor affects all 5 senses neurodegenerative disease any other neurological disease
How are kids harmed because of mercury
affected in womb and breast feeding irritability and emotional problems ADD and lower IQ autism, vaccines- evidence of arm infertility
What are endocrine disruptors because of mercury
mercury affect hypothalamus, pituitary, thyroid, adrenal gland, and gonad
disruptive effects of mercurial on function of thyroid, adrenal, ovary and testis
: Iodiase is enzyme that helps convert T4-> T3 and is inhibited by mercury
How is thyroid affected by mercury
Hypothyroidism
Damage of Thyroid RNA
autoimmune Thyroiditis
Impaired conversion of T2 to active T3
Hashimoto is mercury- also look at other autoimmune disease
TP -antibodies wind down with removal of mercury
What is hormone havoc because of mercury
fatigue weight gain low sex drive cold extremities insomnia hair/skin issues mood swings
How is immune system affected by mercury
binding to sulfhydryl groups on protein may cause immunosuppression of immunostimulation, autoimmune reactions or hypersenisity 14 days after onset of oral mercury exposure, levels of immunoglobulin E and G( IgE and IgG) increase including autoantibodies to biomolecules Lowered resistance to infection prolonged infection allergies autoimmune disease mutagenic
What are toxins
substances produced during metabolism and growth of microorganism and some plant and animal species- primary factor- pathogenicity
What are examples of toxins
viruses- cytotoxin, lysin bacteria-end and exotoxin fungi-mycotoxin protozoa-endotoxin, phospholipase, protease algae-micrycystins plants-alkaloid higher animals
What are mold and mycotoxin
eukaryotic unicellular organism
include mold, yeast and mushroom
more than 100,000 mold species ID
most fungi grow as tubular filament calle hyphae
reproduce and disperse by formation of spores
play a crucial role in nature by breaking down dead organism and releasing their nutrients for reuse
How are fungi beneficial
decomposition: nutrient and carbon recycling
Biosynthetic factories: to produce drugs, antibiotics, alcohol, acids and foods
model organism for biochemical and genetic studies
How are fungi harmful
destruction of food, lumber, paper and cloth
Animal and human disease- including allergies
What is mold secondary metabolism
not essential to maintaining life cycle of mold
give molds that produce a competitive advantage
Types: mycotoxin, volatile organic amount, extracellular, enzyme, extracellular protein
