Liver-and-herbal-medicine.pdf

Liver function
Source of toxins in the body
‡ Xenobiotics
± Environmental chemicals
± food chemicals or contaminant
± drug
± infectious organism
‡ endogenous
± metabolism e.g. steroid hormones, bile acids
± endogenous toxins, e.g.abnormal metabolism,
disease state
Conditions caused or exacerbated
by toxin overload
± CFS
± immune deficienty
± chronic inflammatory
disorders
± allergies
± autoimmune disease
± chemical sensitivities
± cancer
± Liver damage, kidney
damage, etc.
± leaky gut syndrome
(GIT wall damage,
permeated via food
allergy or alcohol)
± almost any chronic
disease process
The bodies protective mechanism
against toxins in body fluid
‡ Storage in adipose tissue
‡ elimination via kidneys, lungs, without any
further processing
‡ elimination via urine, bile, after
biotransformation by the liver
Biotransformation of toxins by
the liver
‡ Purpose is to make it easier for the toxin to
be excreted.
‡ Two reactions
± phase I reactions
± phase II reactions
Phase I
± Involving oxidation or reduction reactions.
± Dependent on enzymes associated with smooth
endoplasmic reticulum (ie microsomes) known
as the mixed function oxidase system (involves
a hemoprotein known as cytochrome P450)
± generally involves exposing or adding a
functional group, usually oxygen, by free
radical mechanism.
± Involves the generation of free radicals.
Bioactivation
± Can result in the production of more toxic
compounds, esp. for xenobiotics, which is
called bioactivation, which can lead to;
‡ tissue damage (e.g. hepatotoxicity, teratogenicity
‡ react with phase II enzymes, made harmless and
excreted
‡ react with a cell protein forming and antigen, which
may lead to immunological reactions such as drug-
induced lupus.
‡ Bind with DNA causing mutations which can lead to
cancer (many carcinogens are first activated by
hepatic microsomes.
Enzyme induction
‡ Both phase I and II enzyme can be induced
ie increased production of enzymes via new
protein synthesis
‡ inducing the the cytochrome P450 enzymes
occur after chronic exposure to ethanol,
some drugs, pesticides, smoking.
‡ Some 50-100 enzymes make up th P450
system.
‡ Phase I directly neutralise some chemicals,
‡ the activity of the enzymes varies between
persons, eg chemical workers in Turin, or
smokers, some get cancer other do not.
Underactive phase I
‡ Experience caffeine intolerance, intolerance
to perfumes, other environmental
chemicals, increase risk of liver disease.
Overactive phase I
‡ Relatively unaffected by caffeine.
‡ Metabolisation by phase I lead;
± to transformation of less toxic form,
± transforming to make it water soluble and then
excreted via the kidneys
± converting the toxin to more chemically active
form, so making it more chemically reactive, so
more easily metabolised by the phase II
enzymes
± Caffeine is directly neutralised by phase I.
Free radicals
‡ For each molecule of toxin metabolised by
phase I , one molecule of free radical is
generated. Without adequate free radical
defenses, every time the liver neutralises a
toxin exposure, it is damaged by the free
radical produced.
Antioxidant
‡ Most important one in the liver is
glutathione, in the process of neutralising
free radicals, glutathione is oxidised to
glutathione disulfide. Glutathione is
required for one of the key phase II
detoxification processes, when high levels
of toxins can lead to glutothione depletion,
and phase II can not occur.
‡ Phase I must be balance by phase II other
wise backlog problem.
± Eg if very active phase I and slow II, usually
people suffere severe toxic reactions to
environmental toxins.
± Large amount of toxin, lead to high activity
phase I, leading to build up.
Substances that activate phase I
detoxification
‡ Drugs; alcohol, nicotine, phenobarbital,
sulfonamides, steroids.
‡ Foods; cabbage, broccoli, sprouts (also stimulate
phase II -indole-3-carbinol-) Charcoal broiled meats,
high protein diet, oranges and tangerines (the last
two also stimulate phase II, -limonene-).
‡ Nutrients; niacin, vitamin B1,C
‡ herbs; caraway, dill seeds, hypericum perforatum.
‡ Environmental toxin; exhaust fumes, paint fumes
pesticides, dioxin.
Inhibitors of phase I
detoxification
‡ Drugs; benzodiazepin, antihistamines,
cimetidine and other antacids, ketoconazole,
sulphaphenazole.
‡ Foods; grapefruit, turmeric, red chili pepper,
clove, onions, marigold.
‡ Other; aging (plus also generally reduced
blood flow through the liver,lack of
physical activity, poor nutrition, toxins from
inappropriate bacteria in the intestines.
Phase II
‡ Involves conjugation; attaching small
chemicals to the toxin, which neutralises the
toxin, or makes it more easily excreted
through the urine or bile.
‡ Some toxins the phase II enzymes act
directly, others have to be activated by
phase I enzymes.
Phase II detoxification pathways
‡ Glutathione conjugation
‡ amino acid conjugation
‡ methylation
‡ sulfation
‡ acetylation
‡ glucuronidation
Glutathione conjugation
‡ Detoxifies
‡ acetaminophen, nicotine, insectisides,
epoxides(carcinogens)
‡ nutrients needed; glutathione, B6
‡ activators
‡ brassical family, limonene foods
‡ inhibitors;
‡ def. of Vit.B2, glutathione, selenium, zinc
‡ clinical indication of dysfunction
‡ chronic chemical exposure, chronic alc.
consumption
Deficiency glutathione
‡ Induced by diseases that increase the need
of glutathione,
‡ or deficiencies of nutrients
‡ or diseases that inhibit its formation;
pulmonary fibrosis, adult respiratory
distress syndrome, HIV, heptic cirrhosis,
cataract formation, due to increased need of
glutathione. Also smoking.
Glutathione
‡ Diet; fresh fruits, vegetables, cooked fish
and meat.
‡ Vit C increases synthesis of glutathione.
500mg a day is enough.
Schisandra chinensis
‡ Enhances hepatic glutathione status, and
induces phase I activity.
‡ Gomisin A; stimulates liver regeneration,
prevents acetaminophgen toxicity, as does
schisandra, improves bile acid metabolism
(Phase II), increases glutothione S-
transferase.
‡ Does not cause harmful bioactivation
‡ dose; 2-3 g per day.
Carduus marianus
‡ Increases the synthesis of glutathione, by
about 35%.
‡ Increase the rate of tissue regeneration
‡ powerful antioxidant, many times more than
Vit. C and E.
‡ also inducer of phase I enzymes.
‡ Shown to protective against several liver
toxic chemicals, its key component is the
prevention of depletion of glutathione by
alcohol or other toxic chemicals.
Brassicas (cruciferous)
‡ Brussels sprouts, broccoli, cabbage,
horseradish, mustard, nasturtium,
watercress,.. Contain sulfer glucosides
know as glucosinolates.
‡ Upon cooking, grating, digestion,steam
distillation; converted to isothiocyanates
which also contain sulfer.
‡ Most potent inducer of phase II enzymes.
‡ Anticancer and cancer preventing activities.
‡ Research shown that 30 g of brussel sprouts
per day increase glutathione levels in liver
and small intestines by 40-50% in males,
not significant increase in females.
Rosemarinus off. And Salvia off.
‡ Carnasol; antioxidant, induces glutothione,
and NAD(P)H:quinone reductase (important
phase II enzymes.
Parsey leaf
‡ Myristicin; inducer of glutathione activity
Citrus fruit oils
‡ Increases glutathione activity
Amino acid conjugation
‡ Detoxifies; benzoate, aspirin
‡ nutrients needed; glycine
‡ activators; glycine
‡ inhibitors; low protein diet
‡ clinical indicators of dysfunction; intestinal
toxicity, toxemia, hepatitis, chronic arthritis,
hypothyroidism, chemical exposure, liver
disorders, carcinomas.
Methylation
‡ Detoxifies; estrogen, dopamine,
ephinephrine, histamine, thiouracil
‡ nutrient needed; S-adenosylmethionine
‡ activators; lipotropic nutrients (choline and
methionine, betaine, folic acid, B12
‡ inhibitors; def. Folic acid or B12
‡ clinical indicators of dysfuncition; PMS.
Estrogen excess, cholestasis, OCP use.
Taraxacum officinalis
‡ Contains choline, also Vit.A,B,C,D,iron,
silicon, Mg,K,Zc,Mang,Phosphorus,
flavonoid glycosides.
‡ Enhances the flow of bile
‡ correct liver imbalances
‡ lipotropic effect; useful for PMS, estrogen
excess.
‡ Anti cancer (breast cancer)
Sulfation
‡ Detoxifies;
± several food additives, toxins from intestinal bacteria, and
environment, several neurotransmitters, aniline dyes,
coumarin, acetamoinphen, methyl-dopa, estrogen,
testoterone, thyroxin
‡ nutrients needed;
± cysteine, methionine, molybdenum
‡ activators; cystein, methionine, taurine
‡ inhibitors;
± tartrazine dye, NSAID eg aspirin, molybdenum
defeciency. Excess molybdenum, B6 (over 100mg per
day)
‡ Clinical indicators of dysfunction;
± intestinal toxicity, parkinsons, alzheimer, RA
Acetylation
‡ Detoxifies; sulfonamide, mescaline
‡ nutrients needed; acetyl-CoA
‡ inhibitors; B2,B5, or C def.
glucuronidation
‡ Detoxifies;
± acetaminophen, morphine, diazepam, digitalis, aspirin,
vanillin, benzoates, menthol and some hormones.
‡ Nutrients needed; glucuronic acid
‡ activators;
± fish oils, limonene containing foods, OCP, smoking,
phenobarbital
‡ inhibitor; aspirin, probenecid
‡ clinical indication of dysfunction;
± gilbert syndrome, yellow discoloration of eyes and skin,
not due to hepatitis.
Sulfoxidation
‡ Is the process by which sulfur containing
molecules in drugs and foods (garlic) are
metabolised. And a process by which the
body eliminates food additives used to
preserve many foods.
‡ The enzyme sulfite oxidase metabolises
sulfite to safer sulfates, which are excreted
in the urine, if poorly function an increased
ration of sulfite to sulfate in urine.
‡ Detoxifies; sulfite, garlic compounds
‡ nutrients needed; molybdenum
‡ activator; molybdenum
‡ clinical indicator of dysfunction; adverse
reaction to sulfer containing foods,
asparagus resulting in strong odour.
‡ Strong odour after eating asparagus, genetic
variability in detoxification via
sulfoxidation.
‡ Poorly functioning; sensitive to sulfer
containing foods and drugs.
Turmeric (Curcuma longa)
‡ Hepatoprotective against several toxins due
to antioxidant activity; chemopreventative
of carcinogenesis
‡ increase in phase II enzyems, and decreases
some phaseI activity
‡ reduces excretion of urinary mutagens in
smokers.
Camelia sinensis
‡ Polyphenolic compounds; pronounced
chemopreventative activity against
carcinogenesis and increase Phase I and
Phase II activity.
‡ Found to prevent damaging effect of
smoking.
‡ Also effecton increasing glutathione levels.
‡ Dose; 1;1 5 - 14 ML PER DAY
Bile excretion
‡ One of the primary routes for the
elimination of modified toxins is through
bile. 2 pints each day.
‡ If inhibited, toxins stay in the liver longer.
‡ Ie cholestasis.
‡ Associated with alteration of liver funcions
test.
‡ Bile is a carrier for toxic substances,
bringing them to the intestines, where the
bile and toxic load are absorbed by fiber
and excreted.
‡ Low fibre diet; reabsorption of toxins.
‡ Bacteria modify toxins to more damaging
forms.
Cholestasis causes
‡ Gallstones
‡ alcohol
‡ endotoxins
‡ hereditary disorders
‡ viral hepatits
‡ hyperthyroidism or
thyroxin
‡ pregnancy
‡ Chemicals; natural and
synthetic hormones