HOPE Cardiometabolic Research Team and Department of Physiology, College of Health Sciences, University of Ilorin, P.M.B. 1515, Ilorin, 240001, Nigeria.
Department of Public Health, Kwara State University, Malete, Nigeria.
Naunyn Schmiedebergs Arch Pharmacol. 2019 Aug;392(8):913-924. doi: 10.1007/s00210-019-01634-1. Epub 2019 Mar 23.
Postpartum contraception is an important step for preventing closely spaced pregnancy. Combined oral contraceptive (COC) has been linked to cardiometabolic disturbances. We therefore hypothesized that postpartum oral estrogen-progestin use induces hepatic lipid accumulation that is associated with glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation via adenosine deaminase (ADA)/xanthine oxidase (XO)/uric acid (UA)-dependent pathway. Female Wistar rats weighing 130-150 g were mated to achieve timed pregnancy and delivery. Twenty-four (24) dams were randomly assigned to receive vehicle (po), COC (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel; po), COC with GR blockade (mifepristone; 80.0 mg/kg; po) and COC with MR blockade (spironolactone; 0.25 mg/kg; po) daily between 3rd and 11th week postpartum. Data showed that postpartum COC resulted in glucose dysregulation, increased visceral adiposity, liver weight, plasma corticosterone, aldosterone, circulating and hepatic free fatty acid (FFA), triglyceride (TG), adenosine deaminase (ADA), uric acid production, lactate production, and oxidative marker injury. On the other hand, G6PD-dependent antioxidant defenses were depressed by postpartum COC. However, these effects were attenuated by GR or MR blockade. Our data demonstrate that enhanced G6PD-dependent antioxidant defenses and suppressed ADA/XO/UA pathway in the liver by GR or MR blockade improves glucose dysregulation and hepatic TG accumulation induced by postpartum COC. This study implies a plausible involvement of GR and MR via defective G6PD-dependent antioxidant barrier and increased activity of ADA/XO/UA pathway in postpartum COC-induced hepatic lipid accumulation.
产后避孕是预防密切间隔妊娠的重要步骤。联合口服避孕药（COC）与心脏代谢紊乱有关。因此，我们假设产后口服雌激素-孕激素的使用会导致肝脏脂质积累，这与通过腺苷脱氨酶（ADA）/黄嘌呤氧化酶（XO）/尿酸（UA）依赖性途径激活糖皮质激素受体（GR）和盐皮质激素受体（MR）有关。体重为 130-150g 的雌性 Wistar 大鼠交配以实现定时妊娠和分娩。24 只（24）只母鼠被随机分为接受载体（po）、COC（1.0μg 乙炔雌二醇和 5.0μg 左炔诺孕酮；po）、GR 阻断（米非司酮；80.0mg/kg；po）和 COC 的 COC）与 MR 阻断（螺内酯；0.25mg/kg；po），产后第 3 至第 11 周每天一次。数据显示，产后 COC 导致葡萄糖失调、内脏脂肪增加、肝重、血浆皮质酮、醛固酮、循环和肝游离脂肪酸（FFA）、甘油三酯（TG）、腺苷脱氨酶（ADA）、尿酸生成、乳酸生成和氧化标记物损伤。另一方面，产后 COC 抑制了 G6PD 依赖性抗氧化防御。然而，这些影响被 GR 或 MR 阻断所减弱。我们的数据表明，GR 或 MR 阻断增强了肝脏中 G6PD 依赖性抗氧化防御，并抑制了 ADA/XO/UA 通路，从而改善了产后 COC 引起的葡萄糖失调和肝 TG 积累。这项研究表明，GR 和 MR 通过 G6PD 依赖性抗氧化屏障缺陷和 ADA/XO/UA 途径活性增加参与产后 COC 诱导的肝脂质积累。
