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![PLANT ALKALOID
• “Alkaloid” refers to diverse group of chemicals of botanical origin which contain heterocyclic
Nitrogen and are generally derived from amino acid.
• Examples of alkaloids are :- cocaine , caffeine , nicotine , morphine , atropine , capsaicin ,
strychnine.
• CAFFEINE
• Caffeine along with its relatives theophylline and theobromine is a xanthine alkaloid and its
physiological effects have been known for centuries: were first deduced from observations of
effects of coffee berries on livestock.
• Xanthines are found in multiple plants including coffee plants , where they probably act to
discourage pests from feeding on plant and inhibit germination of other plant in the
surrounding soil.
• The three xanthines are also found in tea plant [camellia sinensis] and theobroma cacao, the
plant whose seeds are used to produce chocolate.](https://image.slidesharecdn.com/naturaltoxins-231106170336-00073b2f/75/NATURAL-TOXINS-pptx-30-2048.jpg)
![PLANT GLYCOSIDES
• Amygdalin [in almond] and Linamarin [in cassava plant] are classified as cynogenic
glycosides. These compounds serve defensive functions, in that if plant is attacked then;
cynogenic glycoside is broken to release Hydrogen Cyanide.
• Still it is seen that Cassava root is major source of food in Africa but it must be processed in
order to remove all the traces of glycosides.
• Digoxin and Digitalis are steroidal glycosides found in fox glove. These are basically cardiac
glycosides and are Na+/K+ ATPase blockers and have been used to treat variety of
cardiovascular conditions due to effects on myocardial contraction and conductibility.](https://image.slidesharecdn.com/naturaltoxins-231106170336-00073b2f/75/NATURAL-TOXINS-pptx-35-2048.jpg)
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NATURAL TOXINS.pptx
Bacterial toxins can come from a variety of sources including soil, food, and intestinal tracts of animals. They are classified based on their activity (emetic, neurotoxic, enterotoxic) and origin (exotoxins and endotoxins). Common pathogenic bacteria that produce toxins include Bacillus cereus, Clostridium botulinum, C. perfringens, Staphylococcus aureus, and cyanobacteria. Their toxins can cause illnesses like botulism, food poisoning, and toxic shock syndrome. While harmful, some bacterial toxins are being investigated for potential medical applications in cancer treatment and pest control.
NATURAL TOXINS.pptx
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- 3. Sources Sources and reservoirs: soil, mud, water and intestinal tracts of animals Foods: • Improperly canned low-acid foods(green beans, corn, beets, asparagus, mushrooms, spinach) • Smoked fish and fermented food • Improperly home cured hams • Flavoured oil and oil infusions In 1993, FDA required acidification of such preparations to prevent the growth of Clostridia.
- 4. Classification 1. On thebasis of activity Emetic toxins (i.e., Bacillus cereus) Neurotoxins (botulinum toxin) Enterotoxins Cytotoxic enterotoxins Cytotonic enterotoxins
- 5. 2. On thebasis of origin Exotoxins are synthesized and released (usually by Gram-positive bacteria) and are not an integral part of the organism, but may enhance its virulence Eg. diptheria, tetani toxin Endotoxin is generally a lipopolysaccharide membrane constituent released from a dead or dying Gram- negative bacteria, these toxins are nonspecific and stimulate inflammatory
- 6. Bacillus cereus • Gram-positive •Spore forming rod • Aerobe • Cause foodborne illness causing severe nausea, vomiting and diarrhoea • Reservoirs: soil and dust. Toxins Emetic thermostable toxin Diarrheagenic thermolabile toxin • Can survive at 126°C for 90 min • Small cyclic peptide that acts on 5-HT3 receptors stimulating vagus afferent nerve • Serotypes: 1,3 and 8 • Can survive at 56 °C for 20 min • associated with diarrhoea and gastrointestinal pain • Serotypes: 1,2,6,8,10 and 19
- 7. Foods associated • Emeticform: boiled and fried rice • Diarrheal form: wider occurrence and may be found in meats, stews, pudding, sauces, dairy products, vegetable dishes, soups, and meatloaf Confirmed by the isolation of more than 105 B. cereus organisms per gram from epidemiologically implicated food, but such testing is often not done because the illness is relatively harmless and usually self-limiting. Diagnosis Most emetic patients recover within 6–24 hours Prognosis
- 8. Botulinum toxin (Neurotoxin) •Produced by the Clostridium botulinum • Anaerobic • Gram-positive • Spore-forming rod • Commonly found on plants, in soil, water and the intestinal tracts of animals • Food botulism rarely causes illness • Botulinum toxin: • Toxins A,B,E and F in humans • C. butyricum (Type E only) and C.baratti ;toxins C and D in animals • Type G has not caused any human cases • Symptoms: • Drooping eyelids • Double vision • Inability to make facial expression • Difficulty in swallowing LD50 - 1.3– 2.1 ng/kg IV or IM and 10–13 ng/kg when inhaled
- 9. Clostridium perfringens (Enterotoxin) C.perfringens is classified into five types (A–E) depending upon their ability to produce alpha, beta, epsilon, and eta toxin • Primary Reservoir: intestinal tract of warm-blooded animals (including humans) • Food poisoning associated with consumption of roasted meat that has been contaminated with intestinal contents at slaughter, followed by roasting and inadequate storage. • Foods associated with C. perfringens poisoning include cooked meat or poultry, gravy, stew, and meat pies. C. perfringens is also associated with the production of another 11 toxins, including those associated with gas gangrene.
- 10. Staphylococcus aureus • Dangerousand versatile pathogen that can cause a multitude of different diseases • Exoproteins: toxic shock syndrome toxin-1 (TSST-1), the exfoliative toxins ETA and ETB, leukociden and the staphylococcal enterotoxins • Sources: nose and throat discharges, hands and skin, infected cuts, wounds, burns, boils, pimples, and faeces • Primary reservoirs: anterior nares of humans • Other reservoirs: • Mastitic udders of cows (contamination of unpasteurized milk) • Bruised tissues of poultry • Food contaminated after cooking • Keeping food items at room temperature for several hours • Foods associated: • poultry and dressing; sauces and gravy; • Cream filled pastry, potatoes, ham, poultry, fish salads, milk, cheese and generally high protein
- 11. Staphylococcal enterotoxins (SE) •Emesis is produced as the result of stimulation of the putative SE receptors in the abdominal viscera, following which is a cascade of inflammatory mediator release • Properties: • ability to cause emesis and gastroenteritis in primates • Superantigenicity • intermediate resistance to heat and pepsin digestion
- 12. Toxic shock syndrometoxin-1 (TSST-1) • Characterized by low blood pressure, fever, diarrhoea, an extensive skin rash, and shedding of the skin. • TSS results from the massive overproduction of cytokines by T cells induced by the TSST-1. • TSST-1 binds both class II MHC receptors and T-cell receptors, stimulating T-cell responses. • TSST-1 is a superantigen.
- 13. Cyanotoxins are generallygrouped according to their site of action into hepatotoxins, neurotoxins, and dermatotoxins • hepatotoxins are the microcystins, which are produced by a number of cyanobacterial species • including species in the Microcystis, Nostoc, Oscillatoria, and Anabaena genera • produce liver damage through binding to and inhibiting serine/threonine phosphatases, leading to hyperphosphorylation of proteins and disruption of hepatocyte structure and function • Death is caused by hemorrhagic shock which follows the breakdown of liver circulation and accumulation of blood in the liver • At lower chronic exposures, microcystins lead to chronic inflammation.
- 14. • BMAA, anotherneurotoxic cyanotoxin, stimulates glutamate receptors and has been hypothesized to be a causative agent in lytico-bodig, the neurodegenerative disease endemic to Guam. • Saxitoxin, a sodium channel blocker, is also produced by some cyanobacteria (as well as by some dinoflagellates) • Cyanotoxins have been determined to be responsible for toxicity to both wildlife and to domestic livestock. • Growth of cyanobacteria has been observed to reduce growth of green algae as well as aquatic plants such as duckweed and elodea
- 15. Toxin Disease Symptoms Diphtheriatoxin Corynebacterium diphtheriae Diphtheria Begins with sour throat and fever, painful swallowing, difficulty in breathing, formation of grey pseudo membrane covering the tonsils Tetanus toxin Clostridium tetani Tetanus Tetanic spasms, fever, sweating, headache, trouble swallowing, high blood pressure, and a fast heart rate Cholera toxin Vibrio cholerae Cholera watery diarrhoea leading to severe dehydration and electrolyte imbalance. Pertussis toxin Bordetella pertussis Whooping cough initial symptoms similar to common cold with followed by weeks of severe coughing fits. Other bacterial toxins
- 16. Toxins can functionin multiple ways, by inhibiting protein synthesis (diphtheria toxin), • activating second messenger pathways (Bacillus anthracis edema factor or cholera toxin), • activating immune responses (S. aureus superantigens), • damaging cell membranes (E. coli hemolysin), • by general action of metalloprotease activity (Clostridium tetani tetanus toxin).
- 17. Applications of bacterialtoxins • Bacterial toxins are proteins capable of achieving multiple remarkable tasks. They function as autonomous molecular devices, targeting specific cells in an organism, punching holes in their membranes, or modifying intracellular components. • Bacterial toxins, which are primarily harmful, are also being used for the cure of cancer, killing of mosquito larvae.
- 18.
- 19. INTRODUCTION A mycotoxinis a toxic secondary metabolite which is produced by organisms of fungi kingdom , commonly known as molds. One mold species may produced many different mycotoxins, and the same mycotoxin may be produced by several species. Mycotoxins are associated with human disease and cause acute and chronic effect.
- 21. Factors affecting theproduction of mycotoxin Physical factors Temperature between 40 C to 90 Humidity more then 70% Moisture (22- 23%) Chemical factors Nutritional factors, including inorganic ions Use of fungistats Biological Factors Strain of organism Microbial detoxification
- 22. Mechanism Bind toDNA and RNA Oxidative stress Alter protein synthesis and function Alter cell membrane function and transport Alter apoptosis
- 24. Types of mycotoxin Aflatoxin : B1, B2 , G1and G2 Ochratoxin : Ochratoxin A , Ochratoxin B ,Ochratoxin C Citrinin Ergot Alkaloids Patulin Fusarium : Fumonisins , Trichothecenes, Zearalenone. T-2 toxin, Deoxyniba-lenol Deoxynival- lenol(DON)
- 25. Mushroom toxins Toadstoolsare non-edible Amanita caesarea (Caesaer’s mushroom) Amanita Palloides (Death cap) Amanita muscaria (Fly agaric) contain amatoxins, heat-stable peptides amatoxins is the inhibition of RNA polymerase, leading to a blockade of protein synthesis.
- 26. Health effects ofmycotoxins Mycotoxins ae believed to be among the most potent known carcinogen. Effect ranges from immediate toxic responses and immunosuppression to potential long-term teratogenic, estrogenic and estrogenic. Food poisoning Inhibition of protein synthesis Increase of tryptophan in blood and brain Nausea , vomiting Abdominal pain , diarrhoea Breast enlargement in boys immunosuppressor
- 27. Application of mycotoxins Medical application Trichothecenes are known to possess antileukaemic activity. Zearalenone derivatives have been considered as potential treatment for menopausal syndrome in women. Agricultural applcations Derivatives of zearalenone as growth promoter n sheep and cattle ; other have been used as herbicides and insecticides.
- 28.
- 29. INTRODUCTION • Scientist havebeen aware of existing secondary plant products for many years. These are basically chemicals which are manufactured by plant but do not seem to play any role in metabolism, growth, and other life processes. • These products of plant are toxic or repellent to herbivores and microbes and help defending plant producing them. They are evolved as defence mechanism. • First secondary plant product to be isolated and studied is “ MORPHINE’’ in early 1800s . -> The classes of secondary metabolites are :- 1. Alkaloids 2. Terpenes and Terpenoids 3. Glycosides
- 30. PLANT ALKALOID • “Alkaloid”refers to diverse group of chemicals of botanical origin which contain heterocyclic Nitrogen and are generally derived from amino acid. • Examples of alkaloids are :- cocaine , caffeine , nicotine , morphine , atropine , capsaicin , strychnine. • CAFFEINE • Caffeine along with its relatives theophylline and theobromine is a xanthine alkaloid and its physiological effects have been known for centuries: were first deduced from observations of effects of coffee berries on livestock. • Xanthines are found in multiple plants including coffee plants , where they probably act to discourage pests from feeding on plant and inhibit germination of other plant in the surrounding soil. • The three xanthines are also found in tea plant [camellia sinensis] and theobroma cacao, the plant whose seeds are used to produce chocolate.
- 32. PHARMACOLOGICAL ACTIONS • Caffeineis responsible for BLOCKADE OF ADENOSINE RECEPTORS which play a role in modulating release of several neurotransmitters {including dopamine , acetyl choline , glutamate, GABA} • Adenosine receptors are G – Protein coupled receptors and come in four subtypes. Caffeine has highest affinity for A1 and A2 receptors; activation of which leads to suppression of neuronal activity. • Ubiquity of adenosine receptors in brain leads to diverse effects of caffeine to increase alertness, improve mood , decrease reaction times. • Caffeine also increases anxiety. • Chronic consumption is linked to reduction in risk for development of dementia and adenosine receptor blockade. • Discontinuation of chronic caffeine intake :- withdrawl symptoms will be seen. This is due to the adenosine receptors upregulation and increase in number that occur in response to chronic induced adenosine receptors blockade. • Once exposure ceases there is a period of time before compensatory downregulation restores receptor balance. In that interim overabundance of adenosine receptors can lead to other effects i.e increase in cerebral vasodilation which produces classic caffeine withdrawl headache.
- 33. • CAPSAICIN • Itis another alkaloid which is found in plants of genus capsicum , defence against herbivores. • Capsaicin is an agonist at a receptor called transient receptor potential vanilloid 1 receptor (TRPV1). • This receptor is found in variety of areas of mammalian brain and play a role in heat and pain pathways . • Binding of capsaicin to receptors:- induces refractory state , it is used in analgesic preparations. ( although used in combination with other anasthetics to block any unpleasant irritant sensation.
- 34. TERPENES AND TERPENOIDS •Defense mechanism used by plant is production of “latex” a complex fluid released upon injury containing terpenes and terpenoids. • POINSETTIA – A common holiday plant rocketed into notority on the basis of 1944 book reporting unconfirmed death of child followed by ingetion of leaf. • Terpenoids in poinsettias have the potential to irritate human skin – CONTACT DERMITIS
- 35. PLANT GLYCOSIDES • Amygdalin[in almond] and Linamarin [in cassava plant] are classified as cynogenic glycosides. These compounds serve defensive functions, in that if plant is attacked then; cynogenic glycoside is broken to release Hydrogen Cyanide. • Still it is seen that Cassava root is major source of food in Africa but it must be processed in order to remove all the traces of glycosides. • Digoxin and Digitalis are steroidal glycosides found in fox glove. These are basically cardiac glycosides and are Na+/K+ ATPase blockers and have been used to treat variety of cardiovascular conditions due to effects on myocardial contraction and conductibility.
- 36. OTHER IRRITANTS • Dieffenbachiaspecies are examples of plants capable of causing irritation. Colloquially k/a “dumb cane”, these if ingested can produce pair of swelling of mouth , tongue, and oral cavity. This effect has long been attributed to the crystals of Calcium Oxalate (Raphide) which are found in plants. • Raphides are found in Daffodils and also along with variety of alkaloids produce “Daffodils itch” which is common complaint of florists • Sap of stinging nettles (Urtica species) contains a complex mixture of chemicals including formic acid, acetylcholine, and histamine which its stinging hairs (trichomes) can inject into organisms unfortunate enough to brush up against it.
- 37. 1) Dieffenbachia plant 2)Stinging nettles of urtica species
- 38. POISON IVY ANDALLERGIC CONTACT DERMATIS • Allergic contact dermatis involves interaction of plant constituents with immune system to produce an allergic reaction. The plant widely known for this is POISON IVY, (genus- toxicodendron) • Common In North America ,these are responsible for millions of allergic contact dermatis cases per year. • Urushiol is found in roots, leaves and stems of toxicodendron spp. Upon contact with the chemical a rash type develops within a day or two of exposure which will resolve within 2-3 weeks.
- 39.
- 40. CNIDARIA Chironex fleckeri(box jellies) •Long poisonous tentacles • Nematocyst contains venom injected either to prey ,defense or predate. • Shoot out spine-tipped,coiled tubule and delivers toxin. • Venom composition:- proteins(cytolytic)and cardiotoxic components.
- 41. • Significant toxins:-Toxin -1 (CfTX-1)and Toxin-2 (CfTX-2) share features with pore forming toxins. • Mechanism of action :- Pore formation and effect on ion channels • LD50 values of toxins of jellyfish is between 30 and 300 micrograms per kg. • Symptoms:-painful sting,cardiovascular complication, hypertension, hypotension, arrhythmias,respiratory arrest.
- 42. Physalia physalis(Portuguese man‘o’war) • Sting extremely pain rather than lethal. • Colony made of 4 types of zooids:- • 1-polyp(dactylozooids – form tentacles 20 m long) • 2-polyp(pneumatophore-gas filled member used to swim . • 3-polyp(for feeding) and 4-polyp(for reproduction). Nematocyst conatains- enzymes,catalytic peptides,neurotoxins. Symptoms-severe pain,allergies,fever,shock,cardiac problems.
- 43. Arthropodes Class –Arachnida Australian funnelweb spiders • Belong to Atrax genus ,large ,dangerous to humans . • Venom toxic to Na+ ion channels 》Massive release of neurotransmitters 》hypertension》 edema》intracranial hypertension and death of prey. • Ca+,,Na+,K+channel blockers.
- 44. Class –Arachnida andDiplopoda Brown recluse spiders (Loxosceles reclusa) • Necrotic venom rich in –sphingomyelinase, • protease,phosphplipase and hyaluronidase. • Symptoms- itching,swelling,oedema,necrotic area formed. Millipedes • Segmented body,release toxins when pressed. • Body fluids contains toxins(cyanide & quonones) • Symptome-mucous membrane inflammation,blackish brown hyperpigmentation lesion.
- 45. Scorpions –the deadliest Thedeath stalker (Leiurus quinquestriatus) • It is one of the most venomous scorpion. • Venom is a mixture of deadly neuro toxins. • Person will experience extreme pain,convulsions, paralysis and even death due to cardiac and respiratory failure.
- 46. Mollusks Cone snails (Conusspp.) • Venome contains a group of peptides called conotoxins. • Conotoxins mechanism of action-rich in • disulfude bonds ,target Na+,Ca+,K+channels,nicotine and Ach receptors • Have high specificity for binding to targets only in 1 type of prey. • Clinical importance :- Ziconotide in clinical trials for use in pain management.
- 47. Blue-ringed octopus(Hapalochlaena maculosa) • Usestoxins for prey capturing and defense. • Main component of venom is Tetradotxin(TTX). • TTX also found in skin of octupus. • Mechanism of action:-TTX blocks the generation of action potential and blocks Na+ channels . • LD50 of tetradotoxin in mice is around 300 micrograms per kg. • Symptoms:-weakness,numbness,ataxia,higher doses cause paralysis,respiratory arrest and parenthesis.
- 48. Puffer fish secretes Tetrodotoxinis a sodium channel blocker. Stingrays possess barbed and serrated spines which also feature toxin-producing cells. These cells sustain damage when the spine is thrust into target tissue, and some of the toxin enters the wound.
- 49. Neotropical poison dartfrogs ( Dendrobates spp. and Phyllobates spp.). These small, brightly colored frogs secrete alkaloids including batrachotoxin, which locks sodium channels in an open position. Toad secretions can contain epinephrine, norepinephrine, GABA, and serotonin, bufotenine, a hallucinogenic compound. Some new tissues, contain tetrodotoxin.
- 51. • Snake venomis produced in venom glands in the upper jaws and is delivered through ducts to the base of enlarged teeth (fangs). • These teeth often contain grooves, which may be open or closed, and through which the venom flows and is delivered upon biting. Viperidae, the fangs are basically hollow. • Actual injection of venom is produced by action of a muscle on the venom gland and is under the control of the snake. • Snakes typically deliver doses of venom that may be in the range of 100 times the lethal dose for their prey.
- 52. Snake venoms thenon-enzymatic polypeptides • Dendrotoxins (from mamba venoms) which are potassium channel blockers • Cardiotoxins (from cobra venoms) which produce red cell hemolysis • Erabutoxins (from sea snake venom)Cobratoxins which block the nicotinic acetylcholine receptor • Crotamine (from rattlesnake venom) which acts on sodium channels. Antivenom • Monovalent (specific for one species) or polyvalent (active against several species, typically from the same region). Patient may suffer a hypersensitivity reaction
- 53. Gila monster Mexican beadedlizard cobra mambas Rattle Snake
Editor's Notes
- #4 Whereas a proteolytic strain of C. botulinum (Group I) may cause the food to appear and smell “spoiled” (by-products include isobutyric acid, isovaleric acid, and phenylpropionic acid), this is not the case with nonproteolytic strains, many of which can flourish and elaborate toxin at temperatures as low as 3◦C When spore contaminates the food Botul means sausage
- #5 Explain each Emetic- produce their effect by binding to specific receptors in the duodenum, cause vomiting Enterotoxins- action on enteric cells,tell about enteric cells cytotoxic enterotoxins which disrupt the cell membrane or other vital functions of the cell,mostly pore forming,causes the cell to die and cytotonic enterotoxins, which enter the epithelial cell and cause diarrhea without direct membrane disruption or cell death, try and look for examples
- #6 Read about layers Shigella spp., Staphylococcus aureus, orEscherichia coli (which releases the shiga-like vero toxin), can elaborate both endotoxin and exotoxin
- #7 Read about vagus nerve
- #9 Tell about symptoms Droping eyelids Double vision Inability to make facial expression Difficulty in swallowing
- #11 Due to various virulence factors There is a relatively wide degree of molecular diversity among SE toxins and this is thought to be the result of adaptation to allow for a broad range of potential hosts Photo in cow mastic
- #12 Superantigens (SAgs) are proteins produced by bacteria and viruses that are able to stimulate a large proportion of T lymphocytes via interaction with the variable domain of the β chain of the T cell antigen receptor (TCR-Vβ). Only on ingestion of large amounts of SE
- #13 Tell about tampons in menturating women Men and non menstruating women, genitals
- #16 Cleavage of synaptobrevin affects the stability of the SNARE core interfering with exocytosis of neurotransmitters from inhibitory interneurons like gaba and glycine violent spasmatic paralysis ADP- ribosylation of G-protein that controls adenylate cyclase, increase camp conc. Secretion of ions into intestinal lumen, rapid fluid loss and dehydration