Transcript dasd
S2 L9-10 Pro-inflammatory plants Anna Drew Plants producing dermatitis…. • = environmental toxicology • not pollen allergy • Can result from contact with living, damaged or processed plant material • Hazardous in • Industry: timber, cosmetic/perfume, paint/varnish • Environment: walks, gardening • Veterinary: grazing or domestic – mouth areas inflammed, balding – scouring – severe diarrhoea – food not utilised properly • Main clinical problem • identify cause and remove • Treatment • topical corticosteroids • Dermatitis • itching -> scratching -> pain – oedema with blisters that weep. If break can get 2y infection – OR hyperplasia (thickening) of skin. Dries and breaks Plants producing contact dermatitis can be classified into 5 groups: • Mechanical irritants • Stinging nettles • Phototoxic compounds • Allergenic substances • Direct or primary irritants Ref: Evans FJ, Schmidt RJ. Plants and plant products that induce contact dermatitis. Planta Medica 1980: 38(4) Mechanical irritants • Caused by: – Easily detachable rough hairs or bristles on surface of the plant • break off into skin when touched • move around the in the skin causing irritation – or acicular calcium oxalate crystals produced onto plant surface • Found in: – Boroginaceae - Borago, Echium, Pentaglottis, Pulmonaria, Symphytum » Covered with coarse stiff trichomes » highly lignified or produce silica around the hair – Cornaceae - Cornus sanguinea » T shaped trichomes – Malpighiaceae – Malpighia urens – Barley (awns) and other cereal grasses – Cactaceae - Opunta ficus-indica, Opunta cochinillifera (prickly pears) – Narcissus (daffodil), Hyacinthus (hyacinth family) » secrete CaOx onto bulb surface » -> daffodil itch, lily rash which wears off in 12-12 hours Stinging nettles • Caused by: – a defensive trichome which they have evolved • combination of a spring release mechanism + hypodermic syringe • silica (glass) or calcium oxalate tip on surface • when touched tip breaks triggering basal pump mechanism which releases small amount of toxin into the skin • (equiv to muscles or contractile tissue!) tip wound hollow tube • Causes: mild -> very irritant dermatitis, even death – Australia/India • further evolved with enormous hairs to kill animals – UK Tragia involucrata • only one species Urtica dioica • some plants mimic it but do not sting • varies in form according to nutrient value of soil • Composition of poison: – protein peptide material • large molecule – unusual • when dried it denatures • got poison out by dipping leaf in liquid nitrogen and brushing off trichomes onto paper • has properties in common with acetylcholine, histamine, 5-HT • Found in: (over 50 species) – Urticaceae - Urtica, Giardinia, Gyrotaenia, Laportea, Obetia – Euphorbiaceae - Acidoton, Cnesmone, Tragia – (Tragia involucrata – Indian species) – Loasaceae - Loasa, Evertesia, Eucnide – Hydrophyllaceae - Wigandia – lethal ones – Leguminosae - Mucuna pruriens and other Mucuna sp. – trichomes on seed pods – mucunain, a proteinase, on surface responsible for pruritus and mechanical effect for dermatitis Phytotoxic substances • Caused by: – Furanocoumarins (coumarin family) • harmless – animals and humans can eat plants • veterinary problem – photoactivated on skin -> sunburn effect – red inflammation peels to leave brown pigmented areas – around muzzle, hair falls out, look in poor condition – Photoactivated form binds to epidermal DNA and ribosomal RNA • -> pigment 1/3 as active ¼ as active • Found in: – Umbellifereae – Heracleum mantegazzanium, Pastinacea sativa – Rutaceae – Dictamnus albus, Phebalium argentium – Leguminosae – Psoralea sp. – Moraceae – Ficus carica – Rosaceae 6x as active Contact allergens • Most common form of plant dermatitis = allergenic eczematous contact dermatitis • dry scaly erythema -> severe papular/vescicular inflammation with oedema – 1st exposure -> sensitisation (eg 6-25 days) – 2nd exposure -> dermatitis (eg 24 hours) • • • • degree depends on exposure dose hard to diagnose (patch testing) population variability: genetically determined (race, gender) cross sensitization between plants – compounds of same basic chemical structure can cause reaction – elictors – may not be allergenic themselves Sri Lanka • Kandy - plant dermatitis accounted for one third of cases • Clinic incidence affected by: – industrial development of the area – pattern of employment – interest the dermatologist takes in contact dermatitis Ref: Perera WDH. Special problems and perspectives from Sri Lanka. In: See Ket Ng, Chee Leok Goh (Eds). The Principles and Practice of Contact and Occupational Dermatology in the Asia-Pacific Region. World Scientific, 2001 Groups of compounds: • URUSHIOLS = Poison ivy toxins • typical allergenic compounds – simple molecules (low MWt, haptens) – homologous long chain phenolics • R1 and R3 can be -H, -OH or -COOH • R2 can be C9 -> C19 saturated or unsaturated – lipid soluble and will penetrate skin and phenolic groups burn – mechanism of action unknown (direct irritation, allergenic or inflammation) • hard to separate compounds (need GLC) but all work • cross sensitization takes place • 150 derivatives have been found in: – Anacardiaceae • Toxicodendron (poison ivy) • Pentaspadon • Semecarpus (5 species in SL) – medium-sized forest trees found in the wet zone – -> itchy vesicular dermatitis in sensitized individuals – streaks of vesicles correspond to points of contact (face, exposed areas) with the plant – reactions often severe requiring treatment with systemic steroids • Mangifera indica (mango tree) – – – – -> allergic contact dermatitis from contact with stem, leaves, skin of unripe fruit seen on lips and around mouth climbing a tree can produce dermatitis all over body • Anacardium occidentale (cashew nut tree) – -> allergic contact dermatitis – from handling fruit, nut and also from cashew nut oil – Ginkgoaceae - Ginkgo biloba (fruit pulp) – Protaceae - Persiana • SESQUITERPENE LACTONES – Mainly found in Compositae • Allergenic ones also found in: Jubilaceae, Lauraceae – Concentrated in pollen and trichomes • distributed by wind over large areas in spring • distinct from hayfever caused by protein constituents in pollen exine – 250+ characterised - 4 main types structurally: guaiane pseudoguaiane eudesmane germacrane • All essentially have C15 hydrocarbon nuclei • Not all tested on humans (~50) • γ-lactone and α-methylene group -> effect * widely distributed • Found in: – Compositae • • • • • • • Ambrosia Artemisia* Chrysanthemum* Eupatorium* Helenium Iva Parthenium eg Tanacetum parthenium (feverfew) – Jubilaceae • Fruillania – Lauraceae • Laurus Parthenolide • OTHER – Occupational hazards mainly in timber industry (sawing -> dusts) (1) Quinones • in heartwood are responsible Primin Mansenone • Found in: – Primulaceae – Primula obconica Larchol (2) • Not present in the plant under normal circumstances • Formed when plant injured by hydrolysis of tuliposide A -> tulipalin A (enzyme β-glucosidase) • = allergenic material (phytoalexin) • Found in: – Liliaceae and related families » Tulipa, Erythronium, Alstroemeria (3) Volatile oils • low allergenic sensitizing potential (4) Many miscellaneous compounds Primary irritants • Largest group of all • Cause most damage • End up in all kinds of cosmetics, perfumes, soaps, eye makeup – dermatitis common • Burn directly (1st and every exposure) – can be widespread -> severe erythema, itching, flaking etc • Have diverse structures • Not all mechanisms understood – phorbol esters from croton (Euphorbiaceae) best understood • activate protein kinase C – inflammation pathway – some simply acids or phenols which burn • Time for reaction depends on lipid solubility – volatile oils worse – may induce irritation and malignancy at a later stage • Capsaicins & ginger group – Capsaicin = irritant principle found in red pepper family • Solanaceae - Capsicum minimum, C.fructescens • burning effect on membranes throughout GI tract (curry ingredients) • externally -> erythema, no blistering – Gingerols, shagaols • Zingiberaceae – Zingiber officinalis • also capsaicin-like compounds -> rubefacient – Uses: • Go into “deep heat” products – paraffin-based creams for massage, counterirritants to increase blood flow to damaged muscle • Itching powders (mechanical trichome) or chemical irritants • Some foods Capsaicin The gingerols Shogaol – Electron dense centre with lipid side chain • lipophilic, will penetrate cells easily • Volatile oils – – – – Thought to be phenols present if they burnt Now realise terpinoids present Affect certain types of smooth muscle -> spasm (contraction) Mechanism unknown – may block Ca2+ channel – Uses: antibacterial, indigestion preparations Eugenol Safrole Limonene α-pinene – Two groups: aromatics, terpinoids – Beware: cajaput, clove, eucalyptus, nutmeg, pumilopine, rosemary, thyme, terpentine • Proteolytic enzymes – Found in the sap of some plants: • Papain – Carica sp. • Ficia – Ficus sp. • Bromelain – Ananus sp. • Nepenthin - Nepenthus sp. – Eg pitcher plant – insectivorous » insects attracted into modified leaf structure » contains sugary solution with proteolytic enzyme » Insects are a source of nitrogen • On skin -> digestion -> very painful dermatitis • Use: meat industry • Sulphur glycosides – Irritant to mucous membranes • Eg Allium sp. – peeling an onion – eye watering (volatile substances) – when damaged enzymes convert sulphur glycosides -> propenyl sulphuric acid • Mustards – when damaged glucosinolate glycoside -> isothiocyanates (enzyme myrosinase) eg isothiocyanate • Resins – Found in: • Berberidaceae – Podophyllum peltatum – Podophyllum hexandrum Podophyllotoxin – Uses: to burn off worts, (antitumour properties)