Nicotine, commonly known as nicotine, is an organic compound, chemical formula CtenHfourteenNtwo, highly toxic[15]It exists in solanaceous plants (Solanaceae) and is the representative of N-choline receptor agonists. It has paralytic effects on N1 and N2 receptors and the central nervous system, and has no clinical application value.[1]
Nicotine, one of the main alkaloids in tobacco, has a high content in tobacco plants.When smoking or using tobacco products, nicotine will quickly enter the blood circulation through the lungs and then pass to the brain, which is one of the main reasons for smoking addiction.Nicotine can stimulate the central nervous system to produce a series of physiological and psychological effects, including refreshing, improving attention, enhancing emotion, etc.However, due to its addiction, long-term use of tobacco products may lead to physical and mental health problems.
The history of nicotine can be traced back to thousands of years ago, when the ancient Native Americans began to use tobacco.Later, with the European exploration of the Americas, tobacco was introduced into Europe, and gradually became one of the widely used herbs worldwide.Today, nicotine not only exists in traditional tobacco products, but also is extracted and used to manufacture nicotine replacement treatment products (such as nicotine patches, chewing gum, sprays, etc.) to help smokers reduce tobacco dependence in the process of quitting smoking.[14]
Nicotine comes from the scientific name of tobaccoNicotiana tabacumThe scientific name of tobacco is named after Jean Nicot de Villemain, a French resident in Portugal.[1]In 1560, the seeds of tobacco were sent back to Paris from Brazil and popularized for medical use.In 1828, German chemists Poselt and Reimann separated nicotine from tobacco for the first time.In 1843, Melsens proposed the chemical formula of nicotine.Adolf Pinner discovered the structure of nicotine in 1893, and APictet and Crepieux successfully used synthesis to obtain nicotine.[1]
Pharmacological analysis
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Pharmacokinetics
When nicotine enters the body, it will be transmitted through the blood and can pass through the blood-brain barrier. It takes only 7 seconds to reach the brain after inhalation.The blood-brain barrier is a cellular organization between blood and nerve cells in the brain and spinal cord, which plays a role in restricting some macromolecules in the blood from entering the center.The half-life of nicotine in human body is about 2 hours.The amount of nicotine that the body gets from smoking is affected by many factors, including the quality of the cigarette, whether to inhale it in a large mouth, and whether to use a filter.The chewing, oral and inhaled tobacco can enter the body more efficiently by being contained between the lips and gums and inhaled directly through the nose.Liver is the main organ for nicotine metabolism, and the catabolic enzyme is Cytochrome P450 (the main type of catabolic enzyme that plays a role is CYP2A6, and the catabolic enzyme CYP2B6 can also act on nicotine)Cotinine（cotnine）。[6]
pharmacology
Nicotine acts on nicotinic acetylcholine receptors, especiallyAutonomic nerve(α 1) 2 (β 4) 3) andCentral nervous system(α 4) 2 (β 2) 3), the former is located in the medulla of the accessory kidney and other locations, and the latter is located in the central nervous system.At low concentrations, nicotine increases the activity of these receptors. Nicotine also has a slight direct effect on other neurotransmitters, but at high concentrations, it will inhibit these receptors.
For the central nervous system
Nicotine can combine with nicotine acetylcholine receptor to increase the amount of neurotransmitters and dopamine in the brain. Nicotine actually creates a sense of emptiness in the brain. After increasing the concentration through smoking and other ways, it alleviates the emptiness caused by rapid nicotine metabolism, giving people false illusions such as confidence and relaxation caused by smoking,Finally, they may become addicted due to smoking.The smoke produced by tobacco burning containsMonoamine oxidase inhibitor(Monoamine oxidase inhibitor), which can inhibit monoamine oxidase from decomposing monoamine neurotransmitters, such asdopamine、Norepinephrineand5-HTEtc.[7]
For the peripheral nervous system
Nicotine will stimulate the sympathetic nerve and affect the medulla of the accessory kidney by stimulating the visceral nerve, releasing adrenaline.The parasympathetic preganglionic fibers release acetylcholine, which acts on the nicotinic acid acetylcholine receptor to release epinephrine and norepinephrine into the blood.
To the medulla of accessory kidney
Nicotine combines with nicotine receptors in the adrenal medulla to increase the amount of adrenaline in the blood.By combining with the receptor, nicotine depolarizes the cells, and calcium ions flow into them through calcium ion channels. Calcium ions promote nerve cells to release adrenaline and noradrenaline into the blood in the form of secretion. The adrenaline in the blood increases, resulting in faster heartbeat, higher blood pressure, and faster breathing, just like the situation of hyperglycemia.Cotinine is a by-product of nicotine metabolism, which can remain in the blood for 48 hours and can be used to test whether a person smokes.[6]
For oral cell and oral health
Recent evidence shows that nicotine can lead to an increase in the number of cells with DNA aberrations in normal oral epithelial cells, eventually leading to their transformation into malignancy, as well as cell apoptosis and other diseases.It was also found that the oropharyngeal tissues of dogs exposed to nicotine may also suffer from DNA damage such as acanthosis, hyperkeratosis, increased epithelial cell thickness and mucosal melanin deposition.[18][20-21]
Toxicity analysis
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For a long time, people believe that nicotine ingested by smoking induces cancer. New views confirm that nicotine in cigarettes has no direct carcinogenic effect. The real carcinogens are tar and carbon monoxide.[8]
Zhang Yifang, vice president of the China Association of Smoking and Health, said: "Although the scientific and technological community has not yet made a firm statement on whether nicotine can cause cancer, it is true that nicotine can make people addicted to tobacco, and smoking can affect people's health."[9]Nicotine is a very addictive substance.When people inhale smoke or use nicotine products, nicotine will quickly enter the blood through the lungs, and then pass through the blood brain barrier, affecting the dopamine system in the brain, producing pleasure and satisfaction.This sense of pleasure will lead users to rely on nicotine, and it is difficult to quit smoking or use nicotine products.
Nicotine can stimulate the contraction of peripheral blood vessels, increase heart rate, blood pressure and respiration, and promote the occurrence of cardiovascular diseases such as hypertension and stroke.[10]At the same time, it will also affect the respiratory system: smoking or using nicotine products will damage the respiratory system and increase the risk of respiratory diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer.[4]Pregnant women who smoke or use nicotine products may cause premature delivery, low birth weight and other developmental problems.
Main sources
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Nicotine is not only found in tobacco leaves, but also in the fruits of many solanaceous plants. For example, tomato, wolfberry and other plants contain nicotine, and these vegetables and medicinal materials are recognized as healthy food for human health[22-25]。Because of this, the World Health Organization has been vigorously promoting "nicotine replacement therapy" to quit smoking in the world since the 1990s, replacing the nicotine obtained from cigarettes in the past, helping people overcome their dependence on cigarettes physically and psychologically, and increasing the chances of success of quitting smoking more than twice.[9]
The harm of nicotine smoking
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Chronic poisoning
Nicotine is a highly toxic substance. The LD50 of nicotine in rats and mice is 50mg/kg and 3.3mg/kg respectively after oral administration.The nicotine contained in one cigarette can poison a mouse, and the nicotine contained in 20 cigarettes can poison a cow.If a person takes a large amount of nicotine (50 to 70 mg, equivalent to the amount of nicotine in 40 to 60 cigarettes), it may cause death.If you inject nicotine from one cigar or three cigarettes into a person's vein for 3-5 minutes, you will die.Nicotine is not only harmful to higher animals, but also harmful to lower animals, so it is also the main component of agricultural pesticides.[5]
Some people smoke a lot but are not poisoned. The nicotine content is much higher than the lethal dose, but there are few deaths due to acute poisoning. The reason is that some nicotine in tobacco is neutralized by the toxic formaldehyde in the smoke, and most of them do not smoke continuously. These nicotine enters the human body intermittently and slowly[11-13]。In addition, 50% nicotine diffuses into the air with the smoke after the cigarette is ignited, 5% is thrown away with the cigarette end, 25% is burned and destroyed, and only 20% is absorbed by the body.Nicotine is quickly detoxified in the body and excreted in the urine.In addition, long-term smokers have tolerance and addiction to nicotine.[5]
After entering the market, the use rate of electronic cigarettes has grown rapidly worldwide. The liquid of electronic cigarettes contains many harmful substances. The use of electronic cigarettes may cause nicotine addiction, affect the health of various systems of the human body, and even increase the harm of traditional tobacco[3]。At present, there is a legal and regulatory gap in the electronic cigarette market, and there is still a lack of correct guidance, publicity and education for people who try or use electronic cigarettes, especially young people, which is easy to cause some harm.
Obstruction of chemotherapy
In April 2013, American researchers published a research result that nicotine can prevent chemotherapy drugs such as paclitaxel from killing lung cancer cells. This research result may help explain why it is difficult to treat lung cancer patients who smoke.[1]
In a paper published in the Journal of the National Academy of Sciences, American researchers said that the research results showed that the survival rate of patients who did not quit smoking was much lower than that of patients who quit smoking before receiving treatment, which was consistent with the results of clinical research.These findings may also indicate that the treatment of cancer patients who have quit smoking but use nicotine supplements such as nicotine patches and nicotine chewable tablets may not achieve the desired effect.[1]
Scientists used gemcitabine, cisplatin and paclitaxel, three common cancer drugs, to test several different cells extracted from lung cancer tumors.The study found that adding a small amount of nicotine, that is, the amount of nicotine that can be found in the blood of an ordinary smoker, will interfere with the effect of these drugs on lung tumor cells.Nicotine can enhance the activity of two proteins, thus protecting cancer cells.These two proteins can inhibit apoptosis.They said that only when these two genes are suppressed can drugs play a normal role.[1]
Cancer risk
Nicotine itself is not a carcinogen, but the tobacco products containing nicotine, such as cigarettes, cigars, pipes, and other smoking and chewing products containing nicotine, contain a large number of harmful chemicals and carcinogens.Therefore, smoking or using these nicotine containing products is closely related to the risk of cancer.[9]
scientific research
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In 2022, a team of scientists from China and the United States found a kind of intestinal bacteria that can decompose nicotine - Bacteroides xylanolyticus.[16]
Nicotine test
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Cotinine is the main metabolite of nicotine, the burning product of tobacco, which is metabolized in vivo.Because of its long half-life and easy metabolism, cotinine is often used as a tobacco exposure marker for biological samples such as urine, blood or saliva.At present, the rapid detection technology of cotinine mainly includes colorimetry, immunoassay, instrument method and kit[26]。Among them, colorimetry is the simplest and cheapest method to detect cotinine.Its principle is mainly to analyze the optical properties of pyridine ring of cotinine, which is vulnerable to interference from other substances containing pyridine ring[27]Therefore, the specificity and accuracy of the method are reduced, and the measured value is also higher than the true value.Immunoassay is a biological method to detect cotinine by detecting antibodies that can specifically recognize and bind to cotinine. It can be divided into radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA).Instrumental method is to use various analytical instruments to separate cotinine from matrix components and analyze them, such as GC. It is characterized by high cost, high sensitivity, good specificity, detection limit of 0.1 ng/ml, and simultaneous analysis of cotinine and other nicotine metabolites[26]。In addition to the above methods, some European and American companies have developed simple kits to detect cotinine, such as the UK COZART company has developed kits to detect cotinine in serum, urine, saliva and hair.
In addition to the detection of nicotine in human body, it is sometimes necessary to detect nicotine in the environment.In the process of detecting nicotine in the air, there are two ways: active sampling and passive sampling.Active sampling is also called dynamic sampling. The principle is to use a pump to cut off the air sample through the absorption liquid in the collector, so that the gaseous pollutants can be concentrated in the absorption medium, so as to achieve the purpose of concentrated sampling.The international and Chinese tobacco industry adopts active sampling (i.e. pumping air sampling) for the detection of nicotine in the air. Although it is fast and sensitive, the sampling equipment needs power, power and maintenance, which is not suitable for large-scale monitoring.[28]Dynamic sampling does not require any power supply and pumping power. It is a sampling method based on the principle of gas molecular diffusion to collect gaseous or vaporized pollutants in the air, so it is also called pump free sampling method. Its sampling device is a passive sampler.[28]
