However, just a single ricin molecule that enters the cytosol can inactivate over 1, ribosomes per minute and kill the cell. As shown in the diagram, the pathway for internalization of ricin involves: endocytosis by coated pits and vesicles or, endocytosos by smooth pits and vesicles.
The vesicles fuse with an endosome. Many ricin molecules are returned to the cell surface by exocytosis, or the vesicles may fuse to lysosomes where the ricin would be destroyed.
Once inside the cytosol, the RTA catalyzes the depurination of the ribosomes, halting protein synthesis. Ricin can be targeted to specific cells, such as cancer cells , by conjugating the RTA subunit to antibodies or growth factors that preferentially bind the unwanted cells. These immunotoxins have worked very well for in vitro applications, e. Although they have not worked very well in many in vivo situations, progress in this area of research shows promise for the future.
In bone marrow transplant procedures, RTA-immunotoxins have been used successfully to destroy T lymphocytes in bone marrow taken from histocompatible donors. This reduces rejection of the donor bone marrow, a problem called "graft-vs-host disease" GVHD.
Also, in autologous bone marrow transplantation , a sample of the patients own bone marrow is treated with anti-T cell immunotoxins to destroy malignant T-cells in T cell leukemias and lymphomas.
Lord et al. One common problem encountered in patients treated with ricin-immunotoxins is the "vascular leak syndrome", in which fluids leak from blood vessels leading to hypoalbuminemia, weight gain and pulmonary edema. When expressed intracellularly, the toxigene product causes cell death. The introduction and expression of a toxigene in transgenic animals or plants may lead to cell type-specific ablation , which can be used to study developmental cell lineages or to generate animal models of degenerative diseases.
Diagram shows injection of ricin into vagal nerve and subsequent destruction of neurons dashed neurons destroyed, solid neurons unaffected. Neuroscientists can selectively destroy neurons by injecting ricin into nerves. Retrograde axonal transport mechanisms bring the toxin to the neuronal cell bodies where the ribosomes are localized.
Ultrastructural analysis reveals that ricin first causes the dispersion of polyribosomes, and then the rough endoplasmic reticulum disorganizes into smooth vesicles.
The cell bodies perikaryon swell, the nuclei degenerate and the entire neuron disintegrates. Since ricin is a N-acetyl galactosamine-binding lectin, it can be used with different lectins that have different specificities to map neuronal patterns of glycosylation. When suicide transport is observed after injection of the toxin, it confirms the presence of N-acetyl galactosamine residues on the neuronal cell surface.
Strategies in suicide transport work very well in studies of adult peripheral sensory and motor neurons because they are sensitive to ricin. Neurons in the central nervous system of adults are resistant to ablation by ricin, whereas young developing brains are sensitive, suggesting that brain development involves changes in glycosylation of CNS neurons.
The galactose terminal residues may be either clipped or masked by addition of sialic acids residues. In suicide transport experiments, often some ricin leaks out of the nerve , causing systemic poisoning of the animal. This problem can be avoided by simultaneously administering a ricin antiserum. The value of using suicide transport strategies is summarized from Wiley and Oeltmann : anatomical mapping of neurons modeling of motor neuron degenerative diseases studying consequences of peripheral nerve damage and repair mechanisms mapping cellular neurotransmitter receptors disease-related applications including eradication of latent herpes simplex virus in trigeminal sensory neurons production and analysis of glial fibrillary bundles treatment of equine neuromas.
Alber, J. Story Communications Inc. Cooper, M. Czapla, T. Entomol, Lanham,Md. Frankel, A. Once inside, the A chain killer irreversibly inactivates RNA, stopping protein synthesis, leading to cell death. Ricin is estimated to be 6, times more poisonous than cyanide and 12, times more poisonous than rattlesnake venom.
One milligram of ricin can kill an adult. The symptoms of human poisoning begin within a few hours of ingestion. After ingestion, nonspecific symptoms—including nausea, vomiting, diarrhea, and abdominal pain—develop after approximately 12 hours. Ultimately, this progresses to hypotension, liver failure, renal dysfunction, and may progress to death due to multiple organ failure or cardiovascular collapse. After inhalation, symptoms develop within eight hours and include cough, dyspnea, arthralgias, and fever, which may progress to respiratory distress and death, without other organ system manifestations.
Pages: 1 2 Single Page. Topics: castor oil Castor plant Poison Ricin Toxicology. Download PDF. Read More. Hack Oleander Photography is chief of the division of medical toxicology and vice chair for research at East Carolina University in Greenville, North Carolina.
Castor Motor Oils Castor Oil Flavorings Ricin: A Deadly Protein Ricin In Medicine Castor Oil Elixirs P robably everyone at one time in their life has had the rather unpleasant experience of taking castor oil. Attempting to disguise the disagreeable taste with peppermint or fruit juice often results in a permanent dislike for the flavor enhancer as well as the castor oil. Although it is native to the Ethiopian region of tropical east Africa, the castor bean or castor plant Ricinus communis has become naturalized in tropical and warm temperate regions throughout the world, and is becoming an increasingly abundant weed in the southwestern United States.
Castor plants are very common along stream banks, river beds, bottom lands, and just about any hot area where the soil is well drained and with sufficient nutrients and moisture to sustain the vigorous growth. Although the seeds or beans are extremely poisonous, they are the source of numerous economically important products and are one of earliest commercial products.
Castor beans have been found in ancient Egyptian tombs dating back to B. To many people the castor plant is just an overgrown, undesirable weed, and yet it produces one of nature's finest natural oils. The large, tropical, palmately-lobed leaves make this naturalized plant unmistakable. Castor bean plant showing large, tropical, palmately-lobed leaf and cluster of spiny red fruits. On some plants the fruits are green.
Flower cluster inflorescence of castor bean Ricinus communis. The upper spiny balls ovaries with red, star-shaped stigmas are the female flowers. The lower male buds open into whitish-yellow clusters of stamens. The wind-pollinated flowers have no petals. Castor bean fruit Ricinus communis : The spiny, globose seed capsule left dries and splits into 3 sections called carpels center. Each carpel right splits open and forcibly ejects a large seed. In the related Mexican jumping bean Sebastiana pavoniana , a moth occupies each carpel and feeds on the seed tissue inside.
The many "faces" of castor seeds. Like the faces and fingerprints of people, the beautiful designs on castor seeds exhibit infinite genetic variation. The small structure on the end of each seed is a caruncle. The seeds superficially resemble the bodies of ticks, particularly ticks engorged with blood. The seed of candlenut Aleurites molucanna contains about 50 percent oil and burns like a candle. The ancient Polynesians brought this tree to the Hawaiian Islands where it has become naturalized.
The dried nuts were cracked open and the seeds were skewered onto the midrib of a coconut frond or slender bamboo stem and set on fire. Hawaiians also extracted the oil for many other uses: to shine and waterproof wooden bowls, to mix with charcoal to make black canoe paint, to burn as torches, and to burn in stone lamps for light.
The little spiny ovary of the female flower develops into a fruit or seed capsule about the size of a golf ball after pollination. The seed pods may be green, pink, or red depending on the variety , but gradually age to brown. Each spherical, seed capsule is thickly covered with soft flexible spines and has three sections that separate when the seeds are mature. Each section contains one seed that is ejected, often with considerable force, when the carpel splits open. The spiny seed pods may be green L , pink or red C , but eventually turn brown and split open when ripe R.
The shiny, intricately mottled seeds are quite attractive, each with their own unique design in colors of black, gray, brown, yellow-brown, maroon and white. The intricately mottled seeds have a spongy caruncle at one end. Each seed has a small, spongy caruncle at one end which helps absorb water for germination when planted. Seeds remain viable for years. About half the weight of the seed is a thick, yellowish or almost colorless oil that has been used in many industrial applications.
The oil was used in ancient times as fuel for lamps, and is now used in paints and varnishes, for water-resistant coatings, in high-performance motor oils, soap, inks, and plastics. Other derivatives are used in polishes, as solid lubricants, in synthetic perfumes and other products.
Plants are grown commercially for oil production primarily in India and Brazil, but also in some parts of the U. The seeds are extremely poisonous, so keep plants out of reach of children or trim off flowering spike if this is a concern. The toxin in castor seeds is ricin RYE-sin , one of the deadliest natural poisons, estimated as 6, times more poisonous than cyanide and 12, times more poisonous than rattlesnake venom.
As few as four seeds can kill an average-sized adult, while ingestion of lesser amounts will result in vomiting, severe abdominal pain, diarrhea, and convulsions. Livestock and poultry can also be affected if they consume seeds or meal from the seeds.
Although it is a very potent poison, ricin has been investigated as an anti-cancer agent. Since the toxin does not occur in the pure oil, castor oil can be consumed and has been used medicinally as a remedy for everything from constipation to heartburn.
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