Molecular mechanisms for nicotine intoxication

Highlights

• Nicotine, an ingredient in tobacco smoke, is a neurotoxin.

• Nicotine exerts its effects via the stimulation of the nicotinic acetylcholine receptors.

• Nicotine, at higher concentrations, causes acute and chronic intoxications by disrupting the functions of nervous systems.

Abstract

Nicotine, one of the more than 4700 ingredients in tobacco smoke, is a neurotoxin and once used as pesticides in agriculture. Although its use in agriculture is prohibited in many countries, nicotine intoxication is still a problem among the workers in tobacco farms, and young children as well as adults due to the accidental or suicidal ingestions of nicotine products. Understanding the mechanism of nicotine intoxication is important not only for the prevention and treatment but also for the appropriate regulatory approaches. Here, we review pharmacokinetics of nicotine and the molecular mechanisms for acute and chronic intoxication from nicotine that might be relevant to the central and the peripheral nervous system. We include green tobacco sickness, acute intoxication from popular nicotine products, circadian rhythm changes, chronic intoxication from nicotine through prenatal nicotine exposure, newborn behaviors, and sudden infant death syndrome.

Introduction

Nicotine is a water-soluble bioactive alkaloid with potent parasympathomimetic and addictive properties. Nicotine is obtained from the dried leaves and stems of tobacco plant Nicotiana tabacum that grows natively in North and South America. Native Americans (e.g., Anishinaabe-Ojibwe people living around Great Lakes region in America and Canada) began using tobacco in many different ways, such as in religious, ceremonial and medicinal practices thousands years ago and continues the tradition till now (Johnston, 1990; Struthers and Hodge, 2004). Christopher Columbus, in 1492, was offered dried tobacco leaves as a ceremonial gift from the Native Americans (Brooks, 1953). Tobacco was then introduced to Europe for its pleasurable effects and some medicinal use (Charlton, 2004).

Nicotiana tabacum is now cultivated in more than 100 countries, and some 5.73 million metric tons dry weight of tobacco were grown worldwide in 2004 (McKnight and Spiller, 2005). The tobacco plants are now grown in China (39.5% of world total production), Brazil (7.2%), India (8.7%), the US (9.0%) as well as other countries, but these four countries obviously occupy 65% or more of total tobacco production (McKnight and Spiller, 2005; Yoo et al., 2014). However, 80% of tobacco smokers live in low-and middle-income countries where the burden of tobacco-related illness and death is heaviest and tobacco regulatory approaches are not well-established (McKnight and Spiller, 2005; The World Health Organization, 2018b).

Although the number of smokers is declining in developed countries, it is increasing significantly in developing countries thanks to population growth (Ng et al., 2014). Approximately 1.1 billion people smoke tobacco worldwide in 2015, more than half of them reside in eight regions or countries - Bangladesh, Brazil, China, the European Union, India, Indonesia, the Russian Federation, and the United States (Prabhat Jha et al., 2015; The World Health Organization, 2018a). Tobacco is mostly smoked in the form of cigarettes, and an estimated 5.9 trillion cigarettes sold globally in 2006 (Prabhat Jha et al., 2015). Based on these estimates, a smoker smokes average 15 cigarettes a day. Nicotine is the main component found in fresh leaves of tobacco, and the average nicotine content ranges from 2% to 6% of the dry weight of leaves (Gonzalez-Coloma et al., 2010).

Each cigarette contains approximately 8–20 mg of nicotine, the average amount in one cigarette being 12 mg, and merely more than 40 mg nicotine intake at a time is needed to kill an adult (Francisco García Calvo-Flores et al., 2017; Mayer, 2014). Tobacco smoke contains more than 4700 toxic and carcinogenic compounds in addition to nicotine (Talhout et al., 2011; Thielen et al., 2008). Although tobacco smoking itself does not cause immediate death, the tobacco plant has probably been responsible for more deaths, when consider deaths from the tobacco-related cancers and chronic diseases, than any other plants in the world (Charlton, 2004).