Nicotine, fight its effects and get rid of it !
* by Dr Rita Monsieur and Dr Van Snick.
The nicotine is present in many plants, but its main source is in the use of tobacco and replacement therapies such as "transdermal nicotine patches" and "chewing gums". It can pass biological membranes including that of the blood-meningeal barrier. Once absorbed, it is for the most part, metabolized in the liver.
The primary metabolite of nicotine is cotinine which the half-life time is of 15-17h and has a biochemical marker more accessible. In the metabolism of nicotine to cotinine, different cytochrome enzymes P450 (CYP2A6) have been identified and are polymorphic.. This genetic polymorphism may influence the metabolism and contribute to the different needs and habits of smoking.
The predominant effects of nicotine in humans include increased of the heart rate, BP, plasma free fatty acids, mobilization of blood sugar and the increase of catecholamines in the blood.
CHEMICAL PROPERTIES summary
This alkaloid is found in potatoes, tomatoes, black pepper and especially in tobacco. This strong base is a clear liquid that turns brown in oxidizing air and it mixes with water as well as in body fluids.
The absorption increases with pH and can be done through the oral cavity, the lung, bladder, and gastrointestinal tract. Since the pH of an aqueous fraction of the smoke of a cigar is 8.5, that of the pulmonary alveoli 7.4, it is at this level that the absorption will be the most important. The nicotine cannot be reabsorbed through the bladder mucosa if the urinary pH is below 6.
80% of nicotine is C-oxidized by microsomal enzymes in, whose the most important enzyme is the CYP2A6, coumarin 7-hydroxylase in genetic polymorphism. The subjects with genotype *1/*1 have an increased risk for lung cancer. Many other urinary metabolites are formed by N-oxidation and N-methylation as well as by N-and O-glucuronidation.
The nicotine can be excreted by urines, feces, bile, saliva, gastric juice, sweat but also through breast milk. Ascorbic acid increases the urinary excretion of nicotine and cotinine by acidification. The nicotine and their metabolites are also found in children's urines of mothers which smoke. Curiously researches report that daily consumption of nicotine is 18% higher in people whose nicotinic excretion is bigger and concluded that the degree of elimination of nicotine affects the level of daily consumption.
THE BIOLOGICAL EFFECTS OF NICOTINE summary
On the organism summary
Increase of the heart rhythm
Increase of the cardiac contractility
Increase of the blood pressure
Decrease of the body temperature
Mobilization of the blood sugar
Increased free fatty acid blood
Increase of the blood catecholamine
Relaxation
At the cellular level summary
Increase of the synthesis and the secretion of hormones
Activation of the enzyme thyrosine Hydroxylase
Activation of various Transcription factors
Induction of protein heat
Induction of oxidative stress
Effects on apoptosis
Induction of chromosomal aberration
Induction of sister chromatid exchange
1. Effect of nicotine on oxidative stress summary
Nicotine the major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung cancer. The lipid peroxidation and the generation of free radicals are associated processes in the pathogenesis of atherosclerosis.
The rate of this peroxidation is increased in smokers. The administration of nicotine in vivo, causes a decrease of the enzymatic activity of free radicals fighting such as superoxide dismutase (SOD), glutathione peroxidase and catalase.
So the ( OH. ) are involved in many toxic reactions.
The production of superoxide radical ( O2-° ) and hydrogen peroxide (H2O2), damage the alveolar macrophages, and release proteolytic enzymes.
The lipid peroxidation can cause irretrievable damage of the structure of the cell membrane. The release of lactate dehydrogenase (LDH) is witness to this membrane deterioration..
Similarly, the nicotine potentiates the release of superoxide radicals by human neutrophils involved in the pathogenesis of cardiovascular, pulmonary, and neoplastic disorders.
The lipid peroxidation, may also occur in the pancreatic tissue and the esophageal mucosa.
Recently it was suggested that the nicotine sequesters Fe 2+ and inhibits the fenton reaction.
2. The effects on the apoptosis. summary
The nicotine is involved in the development of lung cancer, activates the kinase ERK2 and results in an increase of the expression of the oncogene BCL-2 oncoprotein, and represses apoptosis. In the same study it shows that it blocks the inhibitory activity of PKC and ERK2 anticancer agents in the cancerous lung cells.
This in low concentrations of 1µM of nicotine généralement trouvée dans le sang des fumeurs.
3. Action on the cells proliferation. summary
Nicotine inhibits cell proliferation in a dose dependent and induces significant morphological changes in HL-60 cells.
The inhibition of apoptosis and the stimulation of ectocervical epithelial cells growth and cells lines of human papillomavirus DNA supports the hypothesis of the involvement of nicotine in carcinogenesis.
4. The genotoxic potential of nicotine summary
In some experimental systems we do not find mutagenic inductions. By cons in hamster ovary cells, the increase of chromosomal aberrations and the increase of sister chromatid exchanges are demonstrated and dose-dependent.
The nicotine is genotoxic at concentrations found in the saliva during smoking cessation by using nicotine gums.
5. Effects on gene expression summary
It is shown that nicotine increases the secretion of catecholamines and activates enzymes involved in the biosynthesis of adrenaline from the thyrosine.
One day of exposure to nicotine, increases the expression of the RNAm of the tyrosine hydroxylase and dopamine B-hydroxylase in the medullary cells of the adrenal cortex.
The prenatal exposure to nicotine increases the expression of c-fos protooncogene in the fetal brain and neonatal. It is correlated with the cellular rate of thiols, so the presence of GSH precursors decreases the expression of c-fos.
6. The effect of nicotine on the endocrine system summary
There is a clear influence of smoking on stress hormones of the hypothalamic-pituitary axis such as ACTH (adrenocorticotropic hormone) and cortisol. The symptoms due to stress and symptoms of tobacco abstinence such as anxiety, palpitations, difficulty of concentration and insomnia overlap.
The hypothalamus appears as the main endocrine gland.
The cortisol secreted by the adrenal cortex has the effect of mobilizing energy reserves in the body, reducing the action of the immune system and generally, condition us to respond to all situations of stress. The cortisol may act directly on hypothalamic neurons, but also lots of other neurons outside the hypothalamus.
There are different types of nicotinic receptors in the hypothalamus, in high and low affinity of acetylcholine and other monoaminergic receptors.
|
Studies of receptors summary
Each neurotransmitter exerts its action at postsynaptic level by binding to specific receptors. A neurotransmitter can bind to several types of receptors.
Each receptors which binds to a neurotransmitter constitutes a subtype of receptor The ACh in cholinergic neurons acts on two subtypes of cholinergic receptors : one located in skeletal muscle and the other in cardiac muscle. The inhibitors of neurotransmitters, called antagonists of the receptors, bind to receptors and blocks the normal mechanism of action of the neurotransmitter such as curare for the nicotine. It binds strongly to ACh receptors, present on skeletal muscle cells and blocks the effects of ACh, thereby preventing muscle contraction.
Other pharmacological agents bind to the receptors, but instead of inhibiting them, they mimic the effects of neurotransmitters, synthesized naturally. These are agonists of the receptors. The nicotine, is an example. The nicotine binding to ACh receptors, leads to their activation in muscle. That is why the sensitive ion channels of muscle to ACh are also known as nicotinic cholinergic receptors to distinguish them from other types of ACh receptors, such as those of the heart, which are not sensitive to nicotine but to the muscarine (muscarinic cholinergic receptors). Thus the effects of these two drugs, allowed us to distinguish these two subtypes of ACh receptors. The physiological signal (acetylcholine) or the pharmacological agonist (nicotine) might contribute to stabilize state of open channel allowing passage of ions across the membrane ; the curare, in turn, could stabilize state of channel closed. There are also nicotinic cholinergic receptors in the CNS. It also those, who are involved in tobacco dependence.
In neurons catecholaminergic the neurotransmitters are collectively called catecholamines. These are dopamine (DA), noradrenaline (NA), and adrenaline which the precursor is the thyrosine. These neurons are located in SN regions involved in the regulation of movement, mood, attention, and vegetative functions. The adrenalin is a neurotransmitter of the brain, but it is also released by the suprarenal gland, in the bloodstream. The circulating adrenalin acts on the receptors throughout the body, to meet a coordinated visceral response.
There are few serotonergic neurons in the brain that regulate mood, emotions or sleep. The synthesis of serotonin is limited by the amount of tryptophan available in the extracellular middle. The neurons of amino acids such as glutamate (GLu), glycine (GLy) and gamma-aminobutyric acid (GABA) play the role in most synapses in the CNS. The GABA is contained only in neurons that use it as a neurotransmitter.
|
7. Nicotine and addiction. summary
What they have in common, drugs such as heroin, nicotine, or cocaine ?
These drugs act in fact on systems using different subtypes of neurotransmitterss :
- the system using the opioid peptides for heroin,
- the cholinergic system for nicotine
- or also dopaminergic and noradrenergic systems for cocaine.
These drugs with totally different psychotropic effects have in common to be at the origin of processes related to addiction. This is explained by the fact that they act on the same channels of the motivation of behavior, in this case by the conduct of drug research.
In the case of nicotine and heroin, the most important site of action is represented by the ventral tegmental area at the level of the midbrain, where are the cell bodies of dopaminergic neurons that project to the forebrain through the lateral hypothalamus.
These dopaminergic neurons express on their membrane at once the nicotinic receptors and opiate receptors.
What unites these three psychotropic agents is their ability to stimulate dopamine transmission.
The exact role of dopamine is always a subject of debate.
The blocking of the dopamine receptors decreases the DRUG REWARD which leading to consume more nicotine to keep the same satisfaction.
8. Beneficial effects of nicotine. summary
The nicotine stimulates dopamine neurons and facilitates electrical stimulation of the brain.
The frequency of Parkinson's disease is lower in smokers.
Their effect is anxiolytic by effect on the n AChRs.
The nicotine reduces the weight by reducing the appetite and increases the basic metabolism.
Smoking helps in concentration.
9. Tobacco and heavy metals. summary
One of the methods remediation of soil of heavy metals by phytoremediation is the phytostabilization.
It allows to immobilize the soil pollution (90% of pollutions) to avoid its spread. Heavy metals are not biodegradable and should therefore be removed from the ground.
The research on the hyperaccumulation of these metals by the stems and leaves of certain plants shows that tobacco and mustard give the best performance and we find in their ashes, 40 to 60 ù of Cd, Pb,Cu, Zn (Cadarache study).
A smoker absorbs twice more Cd than a non-smoker and as the Ni is carcinogenic…
The tobacco smoke in the environment (TSE) depends on the number of cigarettes smoked, the proximity of smokers, the room volume and ventilation. The effects of passive exposure to TSE are related to the dose and vary depending on the subject exposed.
In the front line, for smoking cessation AND treat the fatal effects of nicotine ...
Take : DNN Down Nicotine Now : 1 capsule a day by 7 smoked cigarettes In case of prolonged poisoning or exposure to passive smoking...
Take : TMD Toxic Metal Detox the vitamin B complex VB complex M which combines Mg with Vit B will be essential
The awareness of the dangers of smoking, we hope, will motivate to make the decision of abstinence and will remain a crucial factor.
The dramatic potential effects of nAChRs (nicotinic cholinergic receptors) on the neuronal plasticity are increased by nicotine during the prenatal and postnatal exposure and the development during adolescence.
Nicotine alters neuronal morphology, survival, and genetic expression in virtually all examined systems, including the cholinergic system, the dopaminergic, serotoninergic and adrenergic.
Deniz Yildiz., 2004. Nicotine, its metabolism and an overview of its biological effects.Review.Toxicon. 43, 619-632
Mark F. Bear, Barry W. Connors, Michael A. Paradiso.Neurosciences.Editions Pradel.
summary
Back to our natural solutions
send your request