HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, P.M.B. 1515, Nigeria.
Cardiovascular Unit, Department of Physiology, College of Health Sciences, Osun State University, Osogbo, Nigeria.
Mol Cell Biochem. 2021 Apr;476(4):1861-1870. doi: 10.1007/s11010-020-04031-y. Epub 2021 Jan 21.
The kidney plays a critical role in human health and deviation from its normal function can lead to severe morbidity and mortality. Exposure to excess testosterone in women has been linked to several disorders, including kidney disorder and acting undoubtedly through androgen receptor (AR), whereas the involvement of mineralocorticoid receptor (MR) is unclear. Likewise, the renal effect of sodium acetate (SAc) during late gestational exposure to testosterone is not well known. We hypothesized that SAc or MR blockade would protect the kidney of testosterone-exposed pregnant rats against glutathione and adenosine depletion. Twenty-five pregnant Wistar rats were treated (sc) with olive oil, testosterone propionate (0.5 mg/kg) singly or in combination with SAc (200 mg/kg; p.o.), androgen receptor (AR) blocker, flutamide (Flu; 7.5 mg/kg; p.o.) or (MR) blocker, eplerenone (Eple; 0.5 mg/kg) between gestational days 14 and 19. Glutathione, adenosine and nitric oxide were decreased while uric acid (UA), xanthine oxidase (XO), malondialdehyde (MDA), lactate dehydrogenase activity and free fatty acids were increased in the kidneys of gestational rats exposed to testosterone. Also, plasma urea and creatinine were elevated. SAc and Eple reversed tested testosterone-induced effects in gestational rats. The exposure to testosterone impairs renal antioxidant defense via AR and MR during late gestation in pregnant rats. The study also provides evidence that sodium acetate protects the kidneys of gestational testosterone-exposed rats against defective antioxidant defense in like manner as MR or AR antagonist.
肾脏在人类健康中起着至关重要的作用，其功能异常可导致严重的发病率和死亡率。女性体内睾丸酮过多会导致多种疾病，包括肾脏疾病，并通过雄激素受体（AR）发挥作用，而矿物质皮质激素受体（MR）的参与尚不清楚。同样，在妊娠晚期接触睾丸酮期间，醋酸钠（SAc）对肾脏的作用也不明确。我们假设 SAc 或 MR 阻断剂将保护接触睾丸酮的妊娠大鼠的肾脏免受谷胱甘肽和腺苷耗竭的影响。将 25 只妊娠 Wistar 大鼠（sc）用橄榄油、丙酸睾丸酮（0.5mg/kg）、醋酸钠（200mg/kg；po）、雄激素受体（AR）阻断剂氟他胺（7.5mg/kg；po）或（MR）阻断剂依普利酮（0.5mg/kg）单独或联合处理，在妊娠第 14 至 19 天。接触睾丸酮的妊娠大鼠的肾脏中谷胱甘肽、腺苷和一氧化氮减少，尿酸（UA）、黄嘌呤氧化酶（XO）、丙二醛（MDA）、乳酸脱氢酶活性和游离脂肪酸增加，同时血浆尿素和肌酐升高。SAc 和依普利酮逆转了测试中睾丸酮诱导的妊娠大鼠的作用。在妊娠晚期，睾丸酮暴露会通过 AR 和 MR 损害肾脏的抗氧化防御功能。该研究还提供了证据，表明醋酸钠以类似于 MR 或 AR 拮抗剂的方式保护妊娠睾丸酮暴露大鼠的肾脏免受抗氧化防御缺陷的影响。
