Open Access
Suppression of Adenosine Deaminase and Xanthine Oxidase Activities by Mineralocorticoid and Glucocorticoid Receptor Blockades Restores Renal Antioxidative Barrier in Oral Contraceptive-Treated Dam
Author(s) -
Olufunto O. Badmus,
Emmanuel Damilare Areola,
Eleojo Benjamin,
Matthew A. Obekpa,
Tolulope Eniola Adegoke,
Oluwatobi E. Elijah,
Aminu Imam,
Olayemi Joseph Olajide,
Lawrence Aderemi Olatunji
Publication year - 2021
Publication title -
jraas. journal of the renin-angiotensin-aldosterone system/journal of the renin-angiotensin-aldosterone system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 46
eISSN - 1752-8976
pISSN - 1470-3203
DOI - 10.1155/2021/9966372
Subject(s) - endocrinology , medicine , mineralocorticoid receptor , xanthine oxidase , chemistry , aldosterone , biochemistry , enzyme
Objective We tested the hypothesis that postpartum combined oral contraceptive (COC) treatment would induce oxidative stress via the adenosine deaminase-xanthine oxidase pathway in the kidney. We also sought to determine whether mineralocorticoid receptor (MR) or glucocorticoid receptor (GR ) blockade would suppress the activities of ADA and xanthine oxidase caused by postpartum COC treatment in the kidney.Methods Twenty-four Wistar dams were randomly assigned to 4 groups ( n = 6/group). Dams received vehicle (po), COC (1.0 μ g ethinylestradiol and 5.0 μ g 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.Results Data showed that postpartum COC caused increased plasma creatinine and urea, increased renal triglyceride/high-density lipoprotein ratio, free fatty acid accumulation, alanine aminotransferase, gamma-glutamyltransferase, uric acid, and activities of renal XO and ADA. On the other hand, postpartum COC resulted in decreased plasma albumin, renal glutathione, and Na + -K + -ATPase activity with no effect on lactate production. However, MR or GR blockade ameliorated the alterations induced by postpartum COC treatment. The present results demonstrate that MR or GR blockade ameliorates postpartum COC-induced increased activities of ADA and xanthine oxidase and restores glutathione-dependent antioxidative defense.Conclusion These findings implicate the involvements of GR and MR in renal dysfunctions caused by COC in dams via disrupted glutathione antioxidative barrier.