-
International Journal of Environmental... Dec 2016While cotinine is commonly used as a biomarker to validate self-reported smoking status, the selection of an optimal cotinine cutoff value for distinguishing true... (Review)
Review
While cotinine is commonly used as a biomarker to validate self-reported smoking status, the selection of an optimal cotinine cutoff value for distinguishing true smokers from true nonsmokers shows a lack of standardization among studies. This review describes how the cutoff values have been derived, and explains the issues involved in the generalization of a cutoff value. In this study, we conducted an English-language literature search in PubMed using the keywords "cotinine" and "cutoff" or "self-reported" and "smoking status" and "validation" for the years 1985-2014. We obtained 104 articles, 32 of which provided (1) sensitivity and specificity of a cutoff value and (2) determination methods for the given cutoff value. We found that the saliva cotinine cutoff value range of 10-25 ng/mL, serum and urine cotinine cutoff of 10-20 ng/mL and 50-200 ng/mL, respectively, have been commonly used to validate self-reported smoking status using a 2 × 2 table or a receiver operating characteristics (ROC) curve. We also found that recent large population-based studies in the U.S. and UK reported lower cutoff values for cotinine in serum (3 ng/mL) and saliva (12 ng/mL), compared to the traditionally accepted ones (15 and 14 ng/mg, respectively).
Topics: Adult; Biomarkers; Cotinine; Female; Humans; ROC Curve; Saliva; Sensitivity and Specificity; Smoking
PubMed: 27983665
DOI: 10.3390/ijerph13121236 -
Postepy Higieny I Medycyny... Dec 2012This review presents the current state of knowledge on cotinine, the major metabolite of nicotine. Special attention is paid to the formation of this compound in the... (Review)
Review
This review presents the current state of knowledge on cotinine, the major metabolite of nicotine. Special attention is paid to the formation of this compound in the organism, its metabolism, application in diagnostic procedures and evaluation of its in vitro and in vivo activities. For many years, cotinine has been used as a biomarker of exposure to tobacco smoke. Currently, this compound is applied in many other studies including the use of cotinine in the treatment of various diseases. Several years ago, Scott et al. patented therapeutic applications of cotinine in chronic and acute inflammation. Cotinine is an interesting compound with a well-known metabolism; therefore there are suggestions for its application in the diagnosis and treatment of certain diseases.
Topics: Biomarkers; Cotinine; Environmental Exposure; Environmental Monitoring; Humans; Inflammation; Nicotine; Smoke; Tobacco Smoke Pollution
PubMed: 23687219
DOI: 10.5604/17322693.1024156 -
CNS Neuroscience & Therapeutics Jul 2012Tobacco smoking has been correlated with a lower incidence of Alzheimer's disease (AD). This negative correlation has been attributed to nicotine's properties. However,... (Review)
Review
Tobacco smoking has been correlated with a lower incidence of Alzheimer's disease (AD). This negative correlation has been attributed to nicotine's properties. However, the undesired side-effects of nicotine and the absence of clear evidence of positive effects of this drug on the cognitive abilities of AD patients have decreased the enthusiasm for its therapeutic use. In this review, we discuss evidence showing that cotinine, the main metabolite of nicotine, has many of the beneficial effects but none of the negative side-effects of its precursor. Cotinine has been shown to be neuroprotective, to improve memory in primates as well as to prevent memory loss, and to lower amyloid-beta (Aβ)) burden in AD mice. In AD, cotinine's positive effect on memory is associated with the inhibition of Aβ aggregation, the stimulation of pro-survival factors such as Akt, and the inhibition of pro-apoptotic factors such as glycogen synthase kinase 3 beta (GSK3β). Because stimulation of the α7 nicotinic acetylcholine receptors (α7nAChRs) positively modulates these factors and memory, the involvement of these receptors in cotinine's effects are discussed. Because of its beneficial effects on brain function, good safety profile, and nonaddictive properties, cotinine may represent a new therapeutic agent against AD.
Topics: Alzheimer Disease; Animals; Cotinine; Drug Delivery Systems; Humans; Receptors, Nicotinic
PubMed: 22530628
DOI: 10.1111/j.1755-5949.2012.00317.x -
The Journal of Pharmacology and... Mar 2021Nicotine is the major addictive component in tobacco. Cotinine is the major metabolite of nicotine and a weak agonist for nicotinic acetylcholine receptors (nAChRs).... (Comparative Study)
Comparative Study
Nicotine is the major addictive component in tobacco. Cotinine is the major metabolite of nicotine and a weak agonist for nicotinic acetylcholine receptors (nAChRs). Nicotine supports self-administration in rodents. However, it remains undetermined whether cotinine can be self-administered. This study aimed to characterize cotinine self-administration in rats, to compare effects of cotinine to those of nicotine, and to determine potential involvement of nAChRs in cotinine's effects. Adult Wistar rats were trained to self-administer cotinine or nicotine (0.0075, 0.015, 0.03, or 0.06 mg/kg per infusion) under fixed-ratio (FR) and progressive-ratio (PR) schedules. Blood nicotine and cotinine levels were determined after the last FR session. Effects of mecamylamine, a nonselective nAChR antagonist, and varenicline, a partial agonist for 42* nAChRs, on cotinine and nicotine self-administration were determined. Rats readily acquired cotinine self-administration, responded more on active lever, and increased motivation to self-administer cotinine when the reinforcement requirement increased. Blood cotinine levels ranged from 77 to 792 ng/ml. Nicotine induced more infusions at lower doses during FR schedules and greater breakpoints at higher doses during the PR schedule than cotinine. There was no difference in cotinine self-administration between male and female rats. Mecamylamine and varenicline attenuated nicotine but not cotinine self-administration. These results indicate that cotinine was self-administered by rats. These effects of cotinine were less robust than nicotine and exhibited no sex difference. nAChRs appeared to be differentially involved in self-administration of nicotine and cotinine. These results suggest cotinine may play a role in the development of nicotine use and misuse. SIGNIFICANCE STATEMENT: Nicotine addiction is a serious public health problem. Cotinine is the major metabolite of nicotine, but its involvement in nicotine reinforcement remains elusive. Our findings indicate that cotinine, at doses producing clinically relevant blood cotinine levels, supported intravenous self-administration in rats. Cotinine self-administration was less robust than nicotine. Mecamylamine and varenicline attenuated nicotine but not cotinine self-administration. These results suggest cotinine may play a role in the development of nicotine use and misuse.
Topics: Animals; Cotinine; Dose-Response Relationship, Drug; Drug Interactions; Female; Male; Mecamylamine; Nicotine; Rats; Rats, Wistar; Receptors, Nicotinic; Self Administration; Varenicline
PubMed: 33361363
DOI: 10.1124/jpet.120.000367 -
American Journal of Preventive Medicine Feb 2021This study assesses the associations of child salivary cotinine, parent-reported smoking, and child tobacco smoke exposure with the number of child healthcare visits and...
INTRODUCTION
This study assesses the associations of child salivary cotinine, parent-reported smoking, and child tobacco smoke exposure with the number of child healthcare visits and hospital admissions over a 6-month period. This study also assesses the relationships between participant characteristics and child cotinine.
METHODS
Longitudinal data were evaluated from a sample of 313 clinically ill children aged 0-9 years who lived with a smoker and presented to a pediatric emergency department or urgent care in 2016-2018. In 2020, cotinine measurements were log transformed, and Poisson and linear regression were performed.
RESULTS
The majority of the children came from low-income homes (66.1%) and had public insurance/self-pay (95.5%). Child cotinine concentrations ranged from 0.1 to 332.0 ng/mL (geometric mean=4.8 ng/mL, 95% CI=4.1, 5.5). Poisson regression results indicated that each 1-unit increase of log-cotinine concentration was associated with an increase in pediatric emergency department visits over a 6-month period after the baseline visit, with an adjusted RR of 1.16 (95% CI=1.01, 1.34). Each 1-unit increase of log-cotinine concentration was associated with an increase in the frequency of hospital admissions over the 6-month period, with an adjusted RR of 1.50 (95% CI=1.08, 2.09). No differences were found between parent-reported smoking or child tobacco smoke exposure and healthcare utilization. Linear regression results indicated that children who were younger (β= -0.227, p=0.049), were White (geometric mean=5.5 ng/mL), had a medical history of prematurity (geometric mean=8.1 ng/mL), and had a winter baseline visit (geometric mean=6.5 ng/mL) had higher cotinine concentrations. Children living in apartments (geometric mean=5.5 ng/mL) and multiunit homes (geometric mean=5.5 ng/mL) had higher cotinine concentrations than those in single-family homes (geometric mean=3.6 ng/mL).
CONCLUSIONS
Routine biochemical screening could identify children who are in need of intensive tobacco smoke exposure reduction interventions.
Topics: Child; Cotinine; Healthcare Disparities; Humans; Poverty; Smoking; Tobacco Smoke Pollution
PubMed: 33131989
DOI: 10.1016/j.amepre.2020.06.018 -
Current Alzheimer Research 2017The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine that promotes neurogenesis and angiogenesis in the brain. In animal models, it has been shown... (Review)
Review
BACKGROUND
The vascular endothelial growth factor (VEGF) is a neuroprotective cytokine that promotes neurogenesis and angiogenesis in the brain. In animal models, it has been shown that environmental enrichment and exercise, two non-pharmacological interventions that are beneficial decreasing the progression of Alzheimer disease (AD) and depressive-like behavior, enhance hippocampal VEGF expression and neurogenesis. Furthermore, the stimulation of VEGF expression promotes neurotransmission and synaptic plasticity processes such as neurogenesis. It is thought that these VEGF actions in the brain, may underly its beneficial therapeutic effects against psychiatric and other neurological conditions.
CONCLUSION
In this review, evidence linking VEGF deficit with the development of AD as well as the potential role of VEGF signaling as a therapeutic target for cotinine and other interventions in neurodegenerative conditions are discussed.
Topics: Alzheimer Disease; Animals; Cotinine; Humans; Neuroprotective Agents; Vascular Endothelial Growth Factor A
PubMed: 28356047
DOI: 10.2174/1567205014666170329113007 -
Epidemiologic Reviews 1996
Review
Topics: Biomarkers; Cotinine; Environmental Exposure; Humans; Nicotine; Reproducibility of Results; Smoking; Tobacco Smoke Pollution
PubMed: 9021312
DOI: 10.1093/oxfordjournals.epirev.a017925 -
Nihon Rinsho. Japanese Journal of... Sep 1999
-
Biology of Reproduction Aug 2022Levels of cotinine, a major metabolite of nicotine, have been positively correlated with risks of cigarette smoking-related diseases. Melatonin is synthesized by the...
Levels of cotinine, a major metabolite of nicotine, have been positively correlated with risks of cigarette smoking-related diseases. Melatonin is synthesized by the pineal gland and has been demonstrated to be beneficial to oocyte maturation due to its antioxidative activity. In this study, we investigated the effects of cotinine on mouse oocyte meiosis and the protective roles of melatonin in vitro and in vivo. The results showed that cotinine exposure caused defects in the first polar body extrusion and reduced parthenogenetic activation in in vitro-matured oocytes. Additionally, cotinine exposure increased the level of oxidative stress, which resulted in aberrant actin distribution, abnormal spindle morphology, chromosome misalignment, and even oocyte aneuploidy. Simultaneously, cotinine exposure decreased the mitochondrial membrane potential and antioxidant gene expression and increased apoptosis-related gene expression. However, all these toxic effects of cotinine could be reversed after the addition of melatonin, and the mechanism may be a decrease in reactive oxygen species production. In conclusion, cotinine causes poor oocyte quality, which could be rescued by melatonin supplementation during meiotic maturation in mouse oocytes.
Topics: Animals; Antioxidants; Cotinine; Meiosis; Melatonin; Mice; Oocytes; Oogenesis; Oxidative Stress; Reactive Oxygen Species
PubMed: 35191979
DOI: 10.1093/biolre/ioac043 -
Environmental Research May 2021While exposure to secondhand smoke (SHS) is a well-established problem, exposure to third-hand smoke (THS) is scanty known and needs to be studied. The objective of this...
BACKGROUND/OBJECTIVES
While exposure to secondhand smoke (SHS) is a well-established problem, exposure to third-hand smoke (THS) is scanty known and needs to be studied. The objective of this work is to characterize salivary cotinine concentrations among people who self-reported exposure to SHS and THS at home.
METHODS
Cross-sectional study of a representative sample (n = 736) of the adult population (≥16 years) from the city of Barcelona carried out in 2013-2014. A questionnaire on tobacco use and passive exposure was administered, and a saliva sample was collected for cotinine determination. For this study, the information of the non-smoker participants who provided saliva sample (n = 519) was used. The geometric means (GM) and geometric standard deviations (GSD) of the cotinine concentration were compared according to the type of self-reported exposure at home: (1) Not exposed to SHS or THS; (2) Exposed to SHS and THS; and (3) Only exposed to THS. We used log-linear models to compare the cotinine concentration of each exposed group with respect to the unexposed group, adjusting for sex, age, educational level, and tobacco exposure in other settings.
RESULTS
The GM of the salivary cotinine concentration was 0.34 ng/ml (GSD = 0.16) among individuals reporting SHS and THS exposure, 0.22 ng/ml (GSD = 0.15) among those reporting only THS exposure and 0.11 ng/ml (GSD = 0.04) among those who declared not to be exposed to SHS nor THS (p-value for trend <0.001). The regression model showed a statistically significant increase in cotinine concentration among those exposed to SHS and THS (188% higher, 95% CI: 153%; 223%), and only exposed to THS (106% higher, IC95. %: 74.5%; 137.0%) when comparing with the unexposed group. No statistically significant differences in cotinine concentration were observed between those exposed to SHS and THS compared to the THS group (-25.8%, 95% CI: -69.5%; 17.9%).
CONCLUSIONS/RECOMMENDATIONS
People exposed to third-hand smoke at home had quantifiable cotinine levels in saliva. No differences in cotinine levels were found between those exposed to second-hand and third-hand smoke at home. The reduction of exposure to third-hand smoke at home should be put into the agenda of tobacco control.
Topics: Adult; Cotinine; Cross-Sectional Studies; Humans; Saliva; Tobacco Products; Tobacco Smoke Pollution
PubMed: 33129855
DOI: 10.1016/j.envres.2020.110393