Anti-inflammatory and antithrombotic effects of nicotine exposure in oral contraceptive-induced insulin resistance is glucocorticoid-independent

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Date

2016-12-16

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Pharmacological Reports

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 (0.1 mg/kg) or high-dose nicotine (1.0 mg/kg) with or without COC steroids (5.0 µg/kg ethinylestradiol and 25.0 µg/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.

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Keywords

Atherothrombotic CVD, estrogen-progestin oral contraceptive, proinflammatory biomarker, corticosterone

Citation

Olatunji, L.A., Michael, O.S., Adeyanju, O.A., Areola, E.D. & Soladoye, A.O. (2017). Anti-inflammatory and antithrombotic effects of nicotine exposure in oral contraceptive-induced insulin resistance is glucocorticoid-independent. Pharmacological Reports, 69 (3), 512-519, Published by Elsevier. Available online at: Pharmacological Reports | Vol 69, Issue 3, Pages 377-594 (June 2017) | ScienceDirect.com by Elsevier

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