Browsing by Author "Usman, Taofeek Olumayowa"

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    Sildenafil ameliorates leptin resistance and normalizes lipid handling in the hypothalamic and adipose tissues of testosterone-exposed pregnant rats
    (Elsevier, Cell Press, 2021-07-12) Areola, Emmanuel Damilare; Sabinari, Isaiah Woru; Usman, Taofeek Olumayowa; Abayomi, Faith Ifeoluwa; Onyezia, Onyeka; Onaolapo, Bisola; Adetokunbo, Phebe Oluwaseun; Adebanjo, Olympus Oyewole; Oladipupo, Funmilayo Rebecca; Olatunji, Lawrence Aderemi
    Leptin and hypothalamic-adipose lipid handling are relevant in determining the shift of metabolic activities. There are scanty findings connecting glucose dysregulation as a result of hyperandrogenism during gestation to hypothalamic-adipose axis and leptin resistance. Sildenafil has recently gained attention in the prevention of intra-uterine growth restriction. The present study aimed at demonstrating the effect of sildenafil on leptin resistance and hypothalamic-adipose lipid handling in testosterone-exposed pregnant rats. Three groups of pregnant Wistar rats (n ¼ 5/group) received olive oil (Ctr, S.C.) or testosterone propionate (Tes, 3.0 mg/kg; sc)or testosterone propionate (3.0 mg/kg; sc) and sildenafil (Tes þ PDE5, 50 mg/kg; po)from gestational day 14–19. Blood samples, hypothalamus and adipose tissue were excised for biochemical analysis on day 20. Adipose and body weights, plasma leptin and adiponectin, adipose and hypothalamic leptin and triglyceride, adipose uric acid, hypothalamic Nrf2, catalase and nitric oxide were reduced following gestational testosterone exposure. Also, fasting insulin, plasma triglyceride, uric acid, leptin-adiponectin ratio, hypothalamic free fatty acid, total cholesterol, uric acid, aspartate transaminase and cyclic guanine monophosphate were elevated by testosterone exposure to pregnant animals. Sildenafil ameliorated leptin resistance and normalized hypothalamic-adipose lipid handling. Therefore, sildenafil protects against testosterone-induced leptin resistance and adverse hypothalamic adipose lipid handling in pregnant rats.
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    Sildenafil augments fetal weight and placental adiponectin in gestational testosterone-induced glucose intolerant rats
    (Elsevier, 2021-06-14) Areola, Emmanuel Damilare; Adewuyi, Ifeoluwa Jesufemi; Usman, Taofeek Olumayowa; Tamunoibuomi, God’sgift; Arogundade, Lucy Kemi; Olaoye, Barakat; Matt-Ojo, Deborah Damilayo; Jeje, Abdulrazaq Olatunji; Oyabambi, Adewumi Oluwafemi; Afolayan, Enoch Abiodun; Olatunji, Lawrence Aderemi
    Testosterone induces intra-uterine growth restriction (IUGR) with maternal glucose dysregulation and oxidant release in various tissues. Adiponectin, which modulates the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) signaling is expressed in the placenta and affects fetal growth. Sildenafil, a phosphodiesterase type 5 inhibitor (PDE5i), used mainly in erectile dysfunction has been widely studied as a plausible pharmacologic candidate in IUGR. Therefore, the present study sought to determine the effect of PDE5i on placental adipo nectin/Nrf2 pathway in gestational testosterone-induced impaired glucose tolerance and fetal growth. Fifteen pregnant Wistar rats were allotted into three groups (n = 5/group) receiving vehicles (Ctr; distilled water and olive oil), testosterone propionate (Tes; 3.0 mg/kg; sc) or combination of testosterone propionate (3.0 mg/kg; sc) and sildenafil (50.0 mg/kg; po) from gestational day 14–19. On gestational day 20, plasma and placenta homogenates were obtained for biochemical analysis as well as fetal biometry. Pregnant rats exposed to testosterone had 4-fold increase in circulating testosterone compared with control (20.9 ± 2.8 vs 5.1 ± 1.7 ng/mL; p < 0.05) whereas placenta testosterone levels were similar in testosterone- and vehicle-treated rats. Exposure to gestational testosterone caused reduction in fetal and placental weights, placental Nrf2 and adiponectin. Moreover, impaired glucose tolerance, elevated plasma triglyceride-glucose (TyG) index, placental triglyceride, total cholesterol, lactate, malondialdehyde, and alanine aminotransferase were observed in testosterone-exposed rats. Treatment with sildenafil improved glucose tolerance, plasma TyG index, fetal and placental weights and reversed placental adiponectin in testosterone-exposed pregnant rats without any effect on placental Nrf2. Therefore, in testosterone-exposed rats, sildenafil improves impaired glucose tolerance, poor fetal outcome which is accompanied by augmented placental adiponectin regardless of depressed Nrf2.