Lecture 16: Plant Toxin Flashcards
Goitrogens
goiter producing agents
Goiter
- a swelling of thyroid gland
- can be caused by iodine deficiency, which leads to hypothyroidisam,
(hyperplasia of thyroid to compensate for decreased efficacy). - resulted from an autoimmune disease, Hashimoto disease, in which the thyroid gland is gradually destroyed. This also results in hypothyroidism.
- resulted from another autoimmune disease, Grave’s disease, in which
autoantibodies activate TSH receptor and stimulate thyroid growth. This
causes hyperthyroidism.
thyroid hormones
The thyroid hormones act on nearly every cell in the body:
1. increase the basal metabolic rate,
2. affect protein synthesis,
3. help regulate long bone growth (synergy with growth hormone),
4. neuronal maturation
5. increase the body’s sensitivity to catecholamines (such as adrenaline) by permissiveness.
6. regulate protein, fat, and carbohydrate metabolism, affecting how human cells use energetic compounds.
7. stimulate vitamin metabolism.
8. heat generation
Thyroid hormones (T4 and T3) are produced by the follicular cells of the thyroid gland and are regulated by Thyroid-stimulating hormone (TSH) made by the thyrotrophs of the anterior pituitary gland. The effects of T4 in vivo are mediated via T3 (T4 is converted to T3 in target tissues; T3 is 3- to 5- fold more active than T4).
Other Goitrogens
A. iodide trapping (blocked by thiocyanates (SCN-), nitrate (NO3-); SCN- is a detox
product of CN-)
B. organification (inhibited by goitrin in Brassica plants)
C. proteolysis (blocked by excess iodide)
D. deactivation (TCDD, PB can induce UDP-GT;UDP-glucuronyltransferase)
E. peripheral activation (inhibited by R#3)
SCN-, NO3-, goitrin lead to hypoactivity of thyroid—less activity of thyroid.
Excess iodide can also inhibit proteolysis ; deactivation via UDP-GT can be
enhanced by induction of UDP-GT by TCDD, PB deactivate thyroid
MDI—inhibited by R#3 produces hyperactive thyroid
Hypothyroidism symptoms:
- Female infertility, any kind of problems with menstrual cycles
- Poor muscle tone (muscle hypotonia)
- Fatigue
- Hyperprolactinemia and galactorrhea
- Elevated serum cholesterol
- Cold intolerance, increased sensitivity to cold
- Constipation
- Rapid thoughts
- Depression
- Muscle cramps and joint pain
- Thin, brittle fingernails
- Decreased sweating
- Dry, itchy skin
- Weight gain and water retention
- Bradycardia (low heart rate – fewer than sixty beats per minute)
substances that suppress the function of the thyroid gland by interfering with iodine uptake cause an enlargement of the thyroid.
Soybeans (and soybean products such as tofu) Pine nuts Peanuts Millet Strawberries Pears Peaches Spinach Bamboo shoots Radishes Horseradish Vegetables in the genus Brassica
Thyroid Hormone Receptor can be a target for lowering plasma lipids and
weight loss therapy
-Thyroid Hormone reduces plasma cholesterol and triglyceride levels and increases energy expenditure. But it also causes tachycardia.
-The regulation of lipid metabolism is exerted in liver, whereas
the modulation of heart beat is occurred in heart.
Thyroid Hormone Receptors:
a1: widely expressed, especially in cardiac and skeletal muscle
a2: widely expressed, but cannot binds to hormones
b1: Brain, Liver, Kidney
b2: Hypothalamus and pituitary
Cyanogenic glycosides
Cyanogenic glycosides are produced by plants as a defense mechanism in bitter almonds, choke cherry seeds, apple seeds, and cassava (Africa), e.g. amygdalin
Cyanide (CN-) toxicity:
- Acute toxicity: blocks e- transport by blocking cytochrome oxidase in mitochondria (CN—Fe+3 (ferric iron of cyt-ox))
- Chronic tox: metabolism of cyanide to SCN- (thiocyanate)
cassava and -SCN
People who eat cassava have higher SCN- levels in blood and higher incidence of goiter and thyroid cancer.
If sulfur nutriture is sufficient (cysteine), there are less serious chronic effects.
In cysteine (sulfur) deficiency, more serious chronic effects occur.
tropical ataxic neuropathy—optic atrophy, inability to walk properly
tropical amblyopia—optic atrophy
Mode of action: OCN- (cyanate) formation from decreased thiosulfate (S2O3- ) leads to inhibition of glutathione reductase and increased oxidative stress. Cyanate has
neurodegenerative effects.
Ricin:
Some legumes are highly toxic: Castor Bean
Active compound is ricin from Ricinus communis (LD is 2-5 uncooked beans)—castor oil is from steam distillation (protein toxins are destroyed)
mechanism of Ricin
Caster bean –> pre-ricin–> cleavage —> A/B complex (via dithiol linkage) A-S-S-B (active Ricin) –> B chain binds galactose moieties on membrane surface –> enoxytosis of B chain (along with A-chain) –> A-chain is a glycosidase that removes adenine from 28s ribosomal RNA (deactivates ribosome–> blocks protein synthesis
Licorice
Active compound: glycyrrhetinic acid mimics aldosterone action, an agonist for the mineralocorticoid receptor (MR)?
used as sweetening agent
causes Na+, water retention, hypertension, increased blood pressure
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium and water and the release (secretion) of potassium in the kidneys. This increases blood volume and, therefore, increases blood pressure. Many drugs, such as spironolactone, lower blood pressure by blocking the aldosterone receptor.
Aldosterone is a steroid hormone (mineralocorticoid family) produced by the outer-section (zona glomerulosa) of the adrenal cortex in the adrenal gland, and acts on the distal tubules and collecting ducts of the kidney.
Glycyrrhetinic acid
- the affinity of glycyrrhetinic acid for mineralocorticoid receptors is negligibly low.
- Secondly, liquorice has no mineralocorticoid effect in adrenalectomized rats or in patients with Addison’s disease (low cortisol levels).
- the mineralocorticoid effect of glycyrrhetinic acid was restored when liquorice was given together with 11ß-hydroxy-glucocorticosteroids to animals or humans without adrenal function,
- —-> suggesting an interaction between glycyrrhetinic acid and glucocorticoids
Inhibition of 11-hydroxysteroid dehydrogenase type I causes decreased levels of active glucocorticoids
Inhibition of 11-hydroxysteroid dehydrogenase type II causes increased levels of active glucocorticoids
Corticosteroids
are a class of steroid hormones that are produced in the adrenal cortex
