{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T15:10:11Z","timestamp":1751469011360,"version":"3.41.0"},"reference-count":71,"publisher":"Canadian Science Publishing","issue":"11","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p> Elevated circulating uric acid has been postulated to play an important pathophysiological role in estrogen\u2013progestin combined oral contraceptive (COC)-induced hypertension and endothelial dysfunction. We hypothesized that disruption of glucoregulation and liver triglyceride (TG) accumulation induced by COC use would be abated by valproic acid (VPA) treatment through suppression of adenosine deaminase (ADA) and xanthine oxidase (XO) activities. Female Wistar rats aged 9\u201310 weeks were treated with a combination of estrogen\u2013progestin COC steroids (1.0 \u03bcg ethinylestradiol and 5.0 \u03bcg levonorgestrel; p.o.) with or without VPA (100.0 mg\/kg; p.o.) daily for 6 weeks. The result shows that the disrupted glucoregulation and associated elevated hepatic ADA activity, plasma and hepatic XO activity, uric acid (UA), TG\/HDL-cholesterol, total cholesterol, and malondialdehyde induced by COC treatment were attenuated by VPA treatment. However, VPA did not have any effect on plasma aldosterone, corticosterone, ADA, circulating and hepatic free fatty acid. Our results demonstrate that suppression of plasma and hepatic XO activities, along with hepatic ADA activity and UA by VPA treatment, protects against disrupted glucoregulation and increased liver TG by COC independent of elevated corticosteroids. The findings imply that VPA would provide protection against the development of cardiometabolic disorder via inhibition of the ADA\/XO\/UA\u2013mediated pathway. <\/jats:p>","DOI":"10.1139\/cjpp-2018-0231","type":"journal-article","created":{"date-parts":[[2018,7,12]],"date-time":"2018-07-12T21:39:42Z","timestamp":1531431582000},"page":"1092-1103","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of adenosine deaminase and xanthine oxidase by valproic acid abates hepatic triglyceride accumulation independent of corticosteroids in female rats treated with estrogen\u2013progestin"],"prefix":"10.1139","volume":"96","author":[{"given":"Tolulope Eniola","family":"Omolekulo","sequence":"first","affiliation":[{"name":"HOPE Cardiometabolic Research Team, Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel Damilare","family":"Areola","sequence":"additional","affiliation":[{"name":"HOPE Cardiometabolic Research Team, Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olufunto Olayinka","family":"Badmus","sequence":"additional","affiliation":[{"name":"HOPE Cardiometabolic Research Team, Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."},{"name":"Department of Public Health, Kwara State University, Malete, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olugbenga Samuel","family":"Michael","sequence":"additional","affiliation":[{"name":"HOPE Cardiometabolic Research Team, Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."},{"name":"Cardiometabolic Research Unit, Department of Physiology, College of Health Sciences, Bowen University, Iwo, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inkyeom","family":"Kim","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute and Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence Aderemi","family":"Olatunji","sequence":"additional","affiliation":[{"name":"HOPE Cardiometabolic Research Team, Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0225"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.2174\/1389557511009011175"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.05.044"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-017-0574-9"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0804"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(00)00323-4"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2015-000025"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2010.03.027"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1042\/bj0360478"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0535"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60073-2"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1412"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyq126"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2017.12.015"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1130"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1684-1"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.159228"},{"key":"refg18\/ref18","doi-asserted-by":"publisher","DOI":"10.1136\/fn.83.2.F124"},{"key":"refg19\/ref19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0800885"},{"issue":"3","key":"refg20\/ref20","first-page":"293","volume":"21","author":"Finelli C.","year":"2012","journal-title":"J. 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