{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T01:20:22Z","timestamp":1784683222152,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>This study aimed to investigate the effect of antihypertensive drugs on reproductive function in Rattus norvegicus and demonstrate the potential role of oxidative stress in reproductive dysfunction. Rattus norvegicus were selected as the experimental animals and divided into the following groups: healthy (control group), clonidine (CL), rilmenidine (RLD), methyldopa (MTL), amlodipine (ALD), and ramipril (RML). Each individual in each group was marked from one to six. Doses of clonidine (0.075 mg\/kg), rilmenidine (0.5 mg\/kg), methyldopa (100 mg\/kg), amlodipine (2 mg\/kg), and ramipril (2 mg\/kg) were administered orally via gavage to each Rattus norvegicus. Using blood obtained from Rattus norvegicus, the absorbance of the pink-colored complex formed by thiobarbituric acid (TBA) and malondialdehyde (MDA) was measured spectrophotometrically at the 532 nm wavelength. Blood samples were collected from the tail veins to analyze serum malondialdehyde (MDA) and total glutathione levels in the serum of all Rattus norvegicus. After sampling, two mature male Rattus norvegicus were introduced to every group of six female Rattus norvegicus and accommodated in a controlled laboratory environment for two months. Any female Rattus norvegicus that became pregnant during this time was transferred to a solitary cage within a controlled setting. Rattus norvegicus that did not become pregnant and did not give birth during this period were considered infertile. The results were compared among the groups. Total glutathione (tGSH) levels were determined using a spectrophotometer. According to our study, the increase in MDA levels observed was not statistically significant in the CL and RLD groups compared to that in the control group. MDA levels were significantly increased in the methyldopa, amlodipine, and RML groups. While total glutathione levels in the CL group were similar to those in the control group, the RLD, MTL, ALD, and RML groups showed a statistically significant decrease. While the animals in the CL and RLD groups were not infertile, infertility was apparent in the groups treated with MTL, ALD, and RML. Thus, it was determined that the antihypertensive drugs MTL, ALD, and RML had different effects on fertility, and that the use of such drugs could cause infertility by increasing oxidative stress and decreasing antioxidant levels.<\/jats:p>","DOI":"10.3390\/ani14243674","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T04:07:40Z","timestamp":1734667660000},"page":"3674","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Relationship Between Oxidative Stress and Infertility Due to Antihypertensive Drugs in Rattus Norvegicus"],"prefix":"10.3390","volume":"14","author":[{"given":"Berna","family":"Asir","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Erzurum City Hospital, Erzurum 25030, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakup","family":"Kumtepe","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Ankara University, Ankara 06100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mascarenhas, M.N., Flaxman, S.R., Boerma, T., Vanderpoel, S., and Stevens, G.A. (2012). National, regional, and global trends in infertility prevalence since 1990: A systematic analysis of 277 health surveys. PLoS Med., 9.","DOI":"10.1371\/journal.pmed.1001356"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s00404-009-1252-4","article-title":"Comparison of mild stimulation and conventional stimulation in ART outcome","volume":"281","author":"Karimzadeh","year":"2010","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Alcala, M., Gutierrez-Vega, S., Castro, E., Guzman-Guti\u00e9rrez, E., Ramos-\u00c1lvarez, M.P., and Viana, M. (2018). Antioxidants and Oxidative Stress: Focus in Obese Pregnancies. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.01569"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.repbio.2017.03.001","article-title":"Augmented oxidative stress in infertile women with persistent chlamydial infection","volume":"17","author":"Seklic","year":"2017","journal-title":"Reprod. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1080\/13813455.2018.1499120","article-title":"Insulin resistance and oxidative marker in women with PCOS","volume":"126","author":"Bannigida","year":"2018","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12978-018-0506-7","article-title":"A review of the risk factors, genetics and treatment of endometriosis in Chinese women: A comparative update","volume":"15","author":"Dai","year":"2018","journal-title":"Reprod. Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"327240","DOI":"10.1155\/2013\/327240","article-title":"The Effect of Mirtazapine on Cisplatin-Induced Oxidative Damage and Infertility in Rat Ovaries","volume":"2013","author":"Altuner","year":"2013","journal-title":"Sci. World J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/humupd\/dmh021","article-title":"Fertility preservation in female patients","volume":"10","author":"Sonmezer","year":"2004","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"National High Blood Pressure Education Program (2000). Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am. J. Obstet. Gynecol., 183, S1\u2013S22.","DOI":"10.1067\/mob.2000.107928"},{"key":"ref_10","first-page":"92","article-title":"Hypertensive Disorders in Pregnant Women Receiving Fertility Treatments","volume":"12","author":"Barekat","year":"2018","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"106S","DOI":"10.1016\/S0895-7061(00)00226-0","article-title":"Rilmenidine: A clinical overview","volume":"13","author":"Reid","year":"2000","journal-title":"Am. J. Hypertens."},{"key":"ref_12","first-page":"96","article-title":"Investigation of the relationship of some antihypertensive drugs with oxidant\/antioxidant parameters and DNA damage on rat uterus tissue","volume":"5","author":"Salman","year":"2011","journal-title":"Int. J. Fertil. Steril."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3109\/09513590.2010.551564","article-title":"Investigation of the effects of the chronic administration of some antihypertensive drugs on enzymatic and non-enzymatic oxidant\/antioxidant parameters in rat ovarian tissue","volume":"27","author":"Salman","year":"2011","journal-title":"Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jash.2010.03.002","article-title":"Hypertension in pregnancy","volume":"4","author":"Lindheimer","year":"2010","journal-title":"J. Am. Soc. Hypertens. JASH"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Andreucci, V.E., and Fine, L.G. (1991). Treatment of Hypertension During Pregnancy: Drugs to be Avoided and Drugs to be Used. International Yearbook of Nephrology 1992, Springer.","DOI":"10.1007\/978-1-4471-1892-3"},{"key":"ref_16","first-page":"317","article-title":"Calcium supplementation reduces blood pressure during pregnancy: Results of a randomized controlled clinical trial","volume":"70","author":"Villar","year":"1987","journal-title":"Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0272-6386(12)80087-4","article-title":"Prevention and Treatment of Pregnancy-Associated Hypertension: What Have We Learned in the Last 10 Years?","volume":"18","author":"Remuzzi","year":"1991","journal-title":"Am. J. Kidney Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"ref_19","first-page":"153","article-title":"An approach to free radicals in medicine and biology","volume":"492","year":"1980","journal-title":"Acta Physiol. Scand. Suppl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15569543.2018.1474926","article-title":"Pesticides induced oxidative stress and female infertility: A review","volume":"39","author":"Bhardwaj","year":"2018","journal-title":"Toxin Rev."},{"key":"ref_21","first-page":"CD000058","article-title":"Clonidine for smoking cessation","volume":"2008","author":"Gourlay","year":"2004","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuro.2014.05.004","article-title":"Effects of indole-3-carbinol on clonidine-induced neurotoxicity in rats: Impact on oxidative stress, inflammation, apoptosis and monoamine levels","volume":"44","author":"Ahmed","year":"2014","journal-title":"Neurotoxicology"},{"key":"ref_23","first-page":"927214","article-title":"Effect of Clonidine (an antihypertensive drug) treatment on oxidative stress markers in the heart of spontaneously hypertensive rats","volume":"2013","author":"Mustapha","year":"2013","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ejphar.2018.02.001","article-title":"Ameliorative effects of clonidine on ethanol induced kidney injury in rats: Potential role for imidazoline-1 receptor","volume":"824","author":"Elkomy","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_25","first-page":"515","article-title":"A Comparative Investigation of the Nephrotoxic Effects of Various Antihyper-Tensive Drugs in Rats: Biochemical And Histopathological Analysis","volume":"30","author":"Akcay","year":"2014","journal-title":"Acta Medica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0300-8932(04)77185-7","article-title":"The effects of rilmenidine on cardiac autonomic function in healthy volunteers","volume":"57","author":"Onrat","year":"2004","journal-title":"Rev. Esp. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.neuint.2017.01.010","article-title":"MDMA-induced neurotoxicity of serotonin neurons involves autophagy and rilmenidine is protective against its pathobiology","volume":"105","author":"Mercer","year":"2017","journal-title":"Neurochem. Int."},{"key":"ref_28","unstructured":"Catterall, W.A., and Mackie, K. (2006). Goodman & Gildman\u2019s. The Pharmacological Basis of Therapeutics, McGraw Hill. [11th ed.]. Chapter 14."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1159\/000153250","article-title":"Stimulation of erythrocyte cell membrane scrambling by methyldopa","volume":"31","author":"Mahmud","year":"2008","journal-title":"Kidney Blood Press. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.amjhyper.2003.09.007","article-title":"Inhibition of oxidative stress and improvement of endothelial function by amlodipine in angiotensin II-infused rats","volume":"17","author":"Zhou","year":"2004","journal-title":"Am. J. Hypertens."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.amjhyper.2004.05.013","article-title":"Amlodipine attenuates oxidative stress-induced hypertension","volume":"17","author":"Ganafa","year":"2004","journal-title":"Am. J. Hypertens."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"485","DOI":"10.2143\/AC.59.5.2005220","article-title":"Amlodipine and glutathione cycle in hypercholesterolaemia","volume":"59","author":"Mutaf","year":"2004","journal-title":"Acta Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16l","DOI":"10.1016\/S0002-9149(99)00360-4","article-title":"Antioxidant properties of calcium antagonists related to membrane biophysical interactions","volume":"84","author":"Mason","year":"1999","journal-title":"Am. J. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.3390\/toxins5101918","article-title":"Effect of Thioridazine on Erythrocytes","volume":"5","author":"Lang","year":"2013","journal-title":"Toxins"},{"key":"ref_35","first-page":"91.e1","article-title":"Evidence for and against vertical transmission for SARS-CoV-2 (COVID-19)","volume":"223","author":"Amouroux","year":"2020","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ejphar.2007.10.072","article-title":"Benidipine, an anti-hypertensive drug, inhibits reactive oxygen species production in polymorphonuclear leukocytes and oxidative stress in salt-loaded stroke-prone spontaneously hypertensive rats","volume":"580","author":"Matsubara","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1093\/ajh\/hpt272","article-title":"Combination therapy of amlodipine and atorvastatin has more beneficial vascular effects than monotherapy in salt-sensitive hypertension","volume":"27","author":"Zhou","year":"2014","journal-title":"Am. J. Hypertens."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"18","DOI":"10.5830\/CVJA-2010-091","article-title":"Amlodipine attenuates oxidative stress in the heart and blood of high-cholesterol diet rabbits","volume":"23","author":"Salehi","year":"2012","journal-title":"Cardiovasc. J. Afr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2170\/physiolsci.RP012808","article-title":"Ramipril improves oxidative stress-related vascular endothelial dysfunction in db\/db mice","volume":"58","author":"Liang","year":"2008","journal-title":"J. Physiol. Sci. JPS"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1097\/00005344-200210000-00017","article-title":"Oxidative stress in kidney transplant patients with calcineurin inhibitor\u2013induced hypertension: Effect of ramipril","volume":"40","author":"Davis","year":"2002","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jocn.2006.12.003","article-title":"Ramipril protects from free radical induced white matter damage in chronic hypoperfusion in the rat","volume":"15","author":"Kim","year":"2008","journal-title":"J. Clin. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Agarwal, A., Sengupta, P., and Durairajanayagam, D. (2018). Role of L-carnitine in female infertility. Reprod. Biol. Endocrinol. RBE, 16.","DOI":"10.1186\/s12958-018-0323-4"}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/14\/24\/3674\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:56:00Z","timestamp":1760115360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/14\/24\/3674"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,20]]},"references-count":42,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ani14243674"],"URL":"https:\/\/doi.org\/10.3390\/ani14243674","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,20]]}}}