Chemical research in toxicology
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Chem. Res. Toxicol. · Sep 2018
ReviewLipidomics Reveals Changes in Metabolism, Indicative of Anesthetic-Induced Neurotoxicity in Developing Brains.
Numerous studies have demonstrated that treatment with high dose anesthetics for a prolonged duration induces brain injury in infants. However, whether anesthetic treatment leading to neurotoxicity is associated with alterations in lipid metabolism and homeostasis is still unclear. ⋯ Finally, whether lipid changes identified in serum of infant monkeys can serve as indicators for the early detection of anesthetic-induced brain injury is described. We believe extensive studies on alterations in lipids after exposure to anesthetics will allow us to better understand anesthetic-induced neurotoxicity, unravel its underlying biochemical mechanisms, and develop powerful biomarkers for early detection/monitoring of the toxicity.
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Chem. Res. Toxicol. · Jan 2015
ReviewPyrrolizidine Alkaloids: Potential Role in the Etiology of Cancers, Pulmonary Hypertension, Congenital Anomalies, and Liver Disease.
Large outbreaks of acute food-related poisoning, characterized by hepatic sinusoidal obstruction syndrome, hemorrhagic necrosis, and rapid liver failure, occur on a regular basis in some countries. They are caused by 1,2-dehydropyrrolizidine alkaloids contaminating locally grown grain. Similar acute poisoning can also result from deliberate or accidental consumption of 1,2-dehydropyrrolizidine alkaloid-containing herbal medicines, teas, and spices. ⋯ However, these alkaloids are genotoxic and can cause slowly developing chronic diseases such as pulmonary arterial hypertension, cancers, cirrhosis, and congenital anomalies, conditions unlikely to be easily linked with dietary exposure to 1,2-dehydropyrrolizidine alkaloids, especially if clinicians are unaware that such dietary exposure is occurring. This Perspective provides a comprehensive review of the acute and chronic toxicity of 1,2-dehydropyrrolizidine alkaloids and their potential to initiate certain chronic diseases, and suggests some associative considerations or indicators to assist in recognizing specific cases of diseases that may have resulted from dietary exposure to these hazardous natural substances. If it can be established that low-level dietary exposure to 1,2-dehydropyrrolizidine alkaloids is a significant cause of some of these costly and debilitating diseases, then this should lead to initiatives to reduce the level of these alkaloids in the food chain.
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Chem. Res. Toxicol. · Mar 2007
ReviewPossible role of ammonia on the deposition, retention, and absorption of nicotine in humans while smoking.
This perspective presents an overview of the properties of tobacco smoke aerosol and the possible effect of ammonia on the deposition location, retention and the amount and rate of nicotine absorption during cigarette smoking. Three main mechanisms describe the absorption of smoke constituents: (A) gas-phase constituents deposit directly; (B) particles deposit and the constituents then diffuse through the particle into the biological buffer and then into the tissue; and (C) particulate phase constituents evaporate from the particles and then deposit from the gas phase. Nicotine from smoking deposits and is absorbed predominately in the lungs. ⋯ It is certain that no single measurement of tobacco or of smoke, especially one made under equilibrium conditions, can adequately characterize the time-dependent properties of mainstream smoke aerosol. Thus, the fraction of nonprotonated freebase nicotine in trapped, aged smoke particulate matter has not been shown to be a useful predictor of the amount or total rate of nicotine uptake in human smokers. Similarly, "smoke pH" and "pHeff" are not useful practical parameters for providing understanding or predictability of tobacco smoke chemistry or nicotine bioavailability.
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Chem. Res. Toxicol. · Nov 2001
ReviewA consideration of the role of gas/particle partitioning in the deposition of nicotine and other tobacco smoke compounds in the respiratory tract.
Tobacco smoke is an aerosol that contains both gaseous and suspended particulate material (PM). The particles are largely liquid droplets containing a wide variety of condensed organic compounds. Each compound in the smoke will partition between the gas and PM phases and will always seek a state of gas/particle equilibrium. ⋯ This conclusion is consistent with (1) the gas-sampling denuder results obtained by Philip Morris in which significant tobacco smoke nicotine was observed to deposit in acid-coated denuder tubes, with more depositing when the cigarette tobacco blend was treated with ammonia; (2) the view that the sensory "impact" exhibited by some tobacco smokes is caused by the deposition of gaseous nicotine in the pharynx; (3) the observed throat irritation caused by nicotine inhalers; and (4) the high overall respiratory tract deposition efficiencies for nicotine of 0.9 and greater that have been reported for some cigarette smokes. The available information combines to create a picture of nicotine in cigarette smoke that contradicts the traditional view that cigarette smoke PM is typically acidic, with little free-base nicotine typically present in the smoke PM phase. Government agencies interested in establishing a framework for the testing and monitoring of nicotine delivery may wish to consider requiring the measurement and publication of the PM-phase alpha(fb) values for the cigars and cigarettes marketed in their jurisdictions.