title: Anti-inflammatory and antithrombotic effects of nicotine exposure in oral contraceptive-induced insulin resistance are glucocorticoid-independent.
abstract: BACKGROUND
  Reports showed that estrogen-progestin oral contraceptive (COC) or tobacco smoking causes increased risk of cardiovascular diseases (CVD) in premenopausal women. Studies also suggest that nicotine, a major tobacco alkaloid, may worsen or improve atherothrombotic CVD. Altered hemorheology, prothrombotic and pro-inflammatory biomarkers, have been implicated in the development of atherothrombotic CVD events. However, the effect of non-smoking nicotine exposure on these biomarkers during COC treatment is not yet established. We therefore sought to determine the effects of nicotine exposure during COC treatment on these biomarkers, and also tested the hypothesis that the nicotine effects would be glucocorticoid-dependent.
  
  
  METHODS
  Female Sprague-Dawley rats aged 10 weeks were given (po) vehicle, low-dose nicotine (0.1mg/kg) or high-dose nicotine (1.0mg/kg) with or without COC steroids (5.0μg/kg ethinylestradiol and 25.0μg/kg levonorgestrel) daily for 6 weeks.
  
  
  RESULTS
  COC treatment or nicotine exposure led to increased insulin resistance (IR), hemorheological (blood viscosity, hematocrit and plasma viscosity), prothrombotic (plasminogen activator inhibitor-1), pro-inflammatory (uric acid, C-reactive protein, neutrophil/lymphocyte and platelet/lymphocyte ratios) biomarkers and corticosterone. However, these effects except that on corticosterone were abrogated by nicotine exposure during COC treatment.
  
  
  CONCLUSIONS
  Our study indicates that nicotine- or COC-induced IR may be mediated via inflammatory/thrombotic pathway. The results imply that nicotine exposure could impact negatively on atherothrombotic biomarkers in COC non-users, whereas the impact in COC users could be positive. The results also suggest that the anti-inflammatory, antithrombotic and blood viscosity-lowering effects of nicotine exposure during COC use is circulating glucocorticoid-independent.
authors.affiliation: Cardiovascular Research Laboratory, Department of Physiology, College of Health Sciences University of Ilorin, Ilorin, Nigeria. Electronic address: tunjilaw@unilorin.edu.ng.
authors.forename: Lawrence Aderemi
authors.initials: LA
authors.lastname: Olatunji
authors.affiliation: Cardiovascular Research Laboratory, Department of Physiology, College of Health Sciences University of Ilorin, Ilorin, Nigeria.
authors.forename: Olugbenga Samuel
authors.initials: OS
authors.lastname: Michael
authors.affiliation: Cardiovascular Research Laboratory, Department of Physiology, College of Health Sciences University of Ilorin, Ilorin, Nigeria.
authors.forename: Oluwaseun Aremu
authors.initials: OA
authors.lastname: Adeyanju
authors.affiliation: Cardiovascular Research Laboratory, Department of Physiology, College of Health Sciences University of Ilorin, Ilorin, Nigeria.
authors.forename: Emmanuel Damilare
authors.initials: ED
authors.lastname: Areola
authors.affiliation: Cardiovascular Research Laboratory, Department of Physiology, College of Health Sciences University of Ilorin, Ilorin, Nigeria.
authors.forename: Ayodele Olufemi
authors.initials: AO
authors.lastname: Soladoye
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001809:Blood Viscosity / Q000187:drug effects; D003276:Contraceptives, Oral / Q000008:administration & dosage / Q000633:toxicity*; D003345:Corticosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism; D007333:Insulin Resistance; D016912:Levonorgestrel / Q000008:administration & dosage / Q000633:toxicity; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D003276:Contraceptives, Oral; D004338:Drug Combinations; D005343:Fibrinolytic Agents; D005938:Glucocorticoids; D018722:Nicotinic Agonists; C072593:ethinyl estradiol, levonorgestrel drug combination; D004997:Ethinyl Estradiol; D016912:Levonorgestrel; D009538:Nicotine; D003345:Corticosterone
keywords: Atherothrombotic CVD; Corticosterone; Estrogen-progestin oral contraceptive; Proinflammatory biomarker