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

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

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

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

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

.Overactive phase I • Relatively unaffected by caffeine.

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

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

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

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

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

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

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

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

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

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

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

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

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• Shown to protective against several liver toxic chemicals. 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. • also inducer of phase I enzymes. .Carduus marianus • Increases the synthesis of glutathione.

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

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not significant increase in females. .• Research shown that 30 g of brussel sprouts per day increase glutathione levels in liver and small intestines by 40-50% in males.

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

inducer of glutathione activity .Parsey leaf • Myristicin.

Citrus fruit oils • Increases glutathione activity .

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

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

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

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

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

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

which are excreted in the urine. if poorly function an increased ration of sulfite to sulfate in urine. 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. . • The enzyme sulfite oxidase metabolises sulfite to safer sulfates.

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

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

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. .

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

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

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

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

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