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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

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usually oxygen. – 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. by free radical mechanism. – Involves the generation of free radicals. .Phase I – Involving oxidation or reduction reactions.

teratogenicity • react with phase II enzymes. which may lead to immunological reactions such as druginduced lupus.Bioactivation – Can result in the production of more toxic compounds. made harmless and excreted • react with a cell protein forming and antigen. hepatotoxicity. for xenobiotics. esp. • Bind with DNA causing mutations which can lead to cancer (many carcinogens are first activated by hepatic microsomes. which can lead to. • tissue damage (e.g. which is called bioactivation. .

• Some 50-100 enzymes make up th P450 system. pesticides.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. . smoking. some drugs.

eg chemical workers in Turin. . some get cancer other do not.• Phase I directly neutralise some chemicals. or smokers. • the activity of the enzymes varies between persons.

intolerance to perfumes. . increase risk of liver disease. other environmental chemicals.Underactive phase I • Experience caffeine intolerance.

.Overactive phase I • Relatively unaffected by caffeine.

so making it more chemically reactive. . so more easily metabolised by the phase II enzymes – Caffeine is directly neutralised by phase I. – transforming to make it water soluble and then excreted via the kidneys – converting the toxin to more chemically active form. – to transformation of less toxic form.• Metabolisation by phase I lead.

every time the liver neutralises a toxin exposure. .Free radicals • For each molecule of toxin metabolised by phase I . one molecule of free radical is generated. Without adequate free radical defenses. it is damaged by the free radical produced.

when high levels of toxins can lead to glutothione depletion. Glutathione is required for one of the key phase II detoxification processes. . glutathione is oxidised to glutathione disulfide. and phase II can not occur.Antioxidant • Most important one in the liver is glutathione. in the process of neutralising free radicals.

lead to high activity phase I. – Eg if very active phase I and slow II. – Large amount of toxin. usually people suffere severe toxic reactions to environmental toxins. leading to build up. .• Phase I must be balance by phase II other wise backlog problem.

alcohol. • Environmental toxin. • Nutrients. paint fumes pesticides. nicotine. cabbage.Substances that activate phase I detoxification • Drugs.C • herbs. . oranges and tangerines (the last two also stimulate phase II. dill seeds. vitamin B1. dioxin. steroids. • Foods. exhaust fumes. broccoli. hypericum perforatum. phenobarbital. -limonene-). high protein diet. sulfonamides. caraway. niacin. sprouts (also stimulate phase II -indole-3-carbinol-) Charcoal broiled meats.

poor nutrition.lack of physical activity. grapefruit. red chili pepper. toxins from inappropriate bacteria in the intestines. marigold. • Foods. • Other. ketoconazole.Inhibitors of phase I detoxification • Drugs. cimetidine and other antacids. clove. turmeric. aging (plus also generally reduced blood flow through the liver. onions. sulphaphenazole. antihistamines. benzodiazepin. .

others have to be activated by phase I enzymes. or makes it more easily excreted through the urine or bile. • Some toxins the phase II enzymes act directly. . which neutralises the toxin.Phase II • Involves conjugation. attaching small chemicals to the toxin.

Phase II detoxification pathways • • • • • • Glutathione conjugation amino acid conjugation methylation sulfation acetylation glucuronidation .

B6 • activators • brassical family. epoxides(carcinogens) • nutrients needed. nicotine.Glutathione conjugation • Detoxifies • acetaminophen. • def. limonene foods • inhibitors. of Vit. consumption . glutathione. chronic alc.B2. zinc • clinical indication of dysfunction • chronic chemical exposure. glutathione. selenium. insectisides.

. • or deficiencies of nutrients • or diseases that inhibit its formation.Deficiency glutathione • Induced by diseases that increase the need of glutathione. due to increased need of glutathione. pulmonary fibrosis. HIV. Also smoking. cataract formation. adult respiratory distress syndrome. heptic cirrhosis.

cooked fish and meat. . 500mg a day is enough.Glutathione • Diet. vegetables. fresh fruits. • Vit C increases synthesis of glutathione.

increases glutothione Stransferase. and induces phase I activity. • Does not cause harmful bioactivation • dose. as does schisandra. . prevents acetaminophgen toxicity. • Gomisin A.Schisandra chinensis • Enhances hepatic glutathione status. improves bile acid metabolism (Phase II). 2-3 g per day. stimulates liver regeneration.

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• Shown to protective against several liver toxic chemicals. • also inducer of phase I enzymes.Carduus marianus • Increases the synthesis of glutathione. its key component is the prevention of depletion of glutathione by alcohol or other toxic chemicals. C and E. by about 35%. . many times more than Vit. • Increase the rate of tissue regeneration • powerful antioxidant.

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• Upon cooking. cabbage. broccoli. • Anticancer and cancer preventing activities. converted to isothiocyanates which also contain sulfer.. . horseradish. nasturtium. watercress. • Most potent inducer of phase II enzymes..steam distillation. digestion. mustard. grating. Contain sulfer glucosides know as glucosinolates.Brassicas (cruciferous) • Brussels sprouts.

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.• 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.

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Rosemarinus off. and NAD(P)H:quinone reductase (important phase II enzymes. induces glutothione. And Salvia off. . antioxidant. • Carnasol.

inducer of glutathione activity .Parsey leaf • Myristicin.

Citrus fruit oils • Increases glutathione activity .

low protein diet clinical indicators of dysfunction.Amino acid conjugation • • • • • Detoxifies. chemical exposure. intestinal toxicity. chronic arthritis. hypothyroidism. glycine inhibitors. glycine activators. . benzoate. carcinomas. aspirin nutrients needed. hepatitis. toxemia. liver disorders.

dopamine. B12 • inhibitors. Estrogen excess. thiouracil • nutrient needed. PMS. lipotropic nutrients (choline and methionine. folic acid. def.Methylation • Detoxifies. OCP use. S-adenosylmethionine • activators. cholestasis. estrogen. betaine. histamine. ephinephrine. . Folic acid or B12 • clinical indicators of dysfuncition.

Zc.K. • Anti cancer (breast cancer) .A. estrogen excess.D. useful for PMS. • Enhances the flow of bile • correct liver imbalances • lipotropic effect.Mang. silicon.Taraxacum officinalis • Contains choline. flavonoid glycosides.C.iron. Mg.B.Phosphorus. also Vit.

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aniline dyes. toxins from intestinal bacteria. B6 (over 100mg per day) • Clinical indicators of dysfunction. thyroxin • nutrients needed. acetamoinphen. estrogen. – tartrazine dye. and environment. testoterone. . methyl-dopa. methionine. molybdenum defeciency. molybdenum • activators. NSAID eg aspirin. taurine • inhibitors. – several food additives. methionine.Sulfation • Detoxifies. Excess molybdenum. several neurotransmitters. – cysteine. cystein. coumarin.

mescaline • nutrients needed. sulfonamide. . or C def.B5.Acetylation • Detoxifies. B2. acetyl-CoA • inhibitors.

– gilbert syndrome. vanillin. benzoates. OCP. glucuronic acid • activators. aspirin. limonene containing foods. smoking.glucuronidation • Detoxifies. aspirin. not due to hepatitis. probenecid • clinical indication of dysfunction. yellow discoloration of eyes and skin. phenobarbital • inhibitor. morphine. – fish oils. menthol and some hormones. diazepam. • Nutrients needed. digitalis. – acetaminophen. .

And a process by which the body eliminates food additives used to preserve many foods.Sulfoxidation • Is the process by which sulfur containing molecules in drugs and foods (garlic) are metabolised. if poorly function an increased ration of sulfite to sulfate in urine. • The enzyme sulfite oxidase metabolises sulfite to safer sulfates. . which are excreted in the urine.

adverse reaction to sulfer containing foods. sulfite. molybdenum clinical indicator of dysfunction. garlic compounds nutrients needed. molybdenum activator. .• • • • Detoxifies. asparagus resulting in strong odour.

sensitive to sulfer containing foods and drugs. genetic variability in detoxification via sulfoxidation. • Poorly functioning. .• Strong odour after eating asparagus.

.Turmeric (Curcuma longa) • Hepatoprotective against several toxins due to antioxidant activity. and decreases some phaseI activity • reduces excretion of urinary mutagens in smokers. chemopreventative of carcinogenesis • increase in phase II enzyems.

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pronounced chemopreventative activity against carcinogenesis and increase Phase I and Phase II activity. • Found to prevent damaging effect of smoking.Camelia sinensis • Polyphenolic compounds. .

• Also effecton increasing glutathione levels. 1.1 5 .14 ML PER DAY . • Dose.

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2 pints each day.Bile excretion • One of the primary routes for the elimination of modified toxins is through bile. • Associated with alteration of liver funcions test. . • If inhibited. • Ie cholestasis. toxins stay in the liver longer.

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where the bile and toxic load are absorbed by fiber and excreted. • Bacteria modify toxins to more damaging forms. .• Bile is a carrier for toxic substances. • Low fibre diet. reabsorption of toxins. bringing them to the intestines.

natural and synthetic hormones .Cholestasis causes • • • • • • Gallstones alcohol endotoxins hereditary disorders viral hepatits hyperthyroidism or thyroxin • pregnancy • Chemicals.