Michael, Olugbenga SamuelDibia, ChinazaAdeyanju, OluwaseunOlaniyi, KehindeAreola, EmmanuelOlatunji, Lawrence Aderemi2025-05-082025-05-082020-06-0710.Michael, O.S., Dibia, C.L., Adeyanju, O.A., Olaniyi, K.S., Areola, E.D., & Olatunji, L.A. (2020). Estrogen-progestin oral contraceptive and nicotine exposure synergistically confers cardio-renoprotection in female Wistar rats. Biomedicine and Pharmacotherapy, 129, 110387, Published by Elsevier. Available online at: Biomedicine & Pharmacotherapy | Vol 129, September 2020 | ScienceDirect.com by Elsevier10.1016/j.biopha.2020.110387https://uilspace.unilorin.edu.ng/handle/123456789/16407Approximately fifty percent of premenopausal women who smoke cigarettes or on nicotine replacement therapy are also on hormonal contraceptives, especially oral estrogen-progestin. Oral estrogen-progestin therapy has been reported to promote insulin resistance (IR) which causes lipid influx into non-adipose tissue and impairs Na+/K+ -ATPase activity, especially in the heart and kidney. However, the effects of nicotine on excess lipid and altered Na+/K+ -ATPase activity associated with the use of estrogen-progestin therapy have not been fully elucidated. This study therefore aimed at investigating the effect of nicotine on cardiac and renal lipid influx and Na+/K+ -ATPase activity during estrogen-progestin therapy. Twenty-four female Wistar rats grouped into 4 (n = 6/group) received (p.o.) vehicle, nicotine (1.0 mg/kg) with or without estrogen-progestin steroids (1.0 μg ethinyl estradiol and 5.0 μg levonorgestrel) and estrogen-progestin only daily for 6 weeks. Data showed that estrogen-progestin treatment or nicotine exposure caused IR, hyperinsulinemia, increased cardiac and renal uric acid, malondialdehyde, triglyceride, glycogen synthase kinase-3, plasminogen activator inhibitor-1, reduced bilirubin and circulating estradiol. Estrogen-progestin treatment led to decreased cardiac Na+/K+-ATPase ac tivity while nicotine did not alter Na+/K+-ATPase activity but increased plasma and tissue cotinine. Renal Na+/K+-ATPase activity was not altered by the treatments. However, all these alterations were reversed following combined administration of oral estrogen-progestin therapy and nicotine. The present study therefore demon strates that oral estrogen-progestin therapy and nicotine exposure synergistically prevents IR-linked cardio-renotoxicity with corresponding improvement in cardiac and renal lipid accumulation, oxidative stress, in- flammation and Na+/K+-ATPase activityenEstrogen-progestin therapyCardiacNa+-K+-ATPase activityLipidInsulin resistanceMetabolic stressNicotineArticle