Rahmi Aslan , Kerem Taken , Akif Erbin , Hamit Hakan Alp , Recep Eryilmaz , Omer Sarilar , Zubeyir Huyut
{"title":"睾酮和磷酸二酯酶-5抑制剂组合对氧化应激标志物、基质金属蛋白酶和DNA氧化损伤的协同作用：一项随机对照实验研究。","authors":"Rahmi Aslan , Kerem Taken , Akif Erbin , Hamit Hakan Alp , Recep Eryilmaz , Omer Sarilar , Zubeyir Huyut","doi":"10.1016/j.androl.2020.10.011","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>To investigate the effects of combined tadalafil and testosterone usage on oxidative stress, DNA damage and MMPs in testosterone deficiency.</p></div><div><h3>Methods</h3><p>Fifty rats were randomly divided into 5 groups (<em>group-1:</em> sham group-placebo, g<em>roup-2:</em> bilateral orchiectomy (ORX), g<em>roup-3</em>: bilateral ORX<!--> <!-->+<!--> <!-->tadalafil, g<em>roup-4</em>: bilateral ORX<!--> <!-->+<!--> <!-->testosterone, g<em>roup-5</em>: bilateral ORX<!--> <!-->+<!--> <!-->tadalafil<!--> <!-->+<!--> <!-->testosterone). Group-3 received tadalafil (5<!--> <!-->mg/kg/day, oral). Group-4 was administered testosterone undecanoate (100<!--> <!-->mg/kg i.m., single dose). Group-5 was administered a combination of <em>tadalafil</em> and testosterone undecanoate. <em>All groups were compared</em> with regard to <em>serum</em> nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX-4), total thiol, matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels.</p></div><div><h3>Results</h3><p>Total thiol levels of group-2 were significantly lower than the other groups and thiol levels were higher in group-1 and group-5 than in the other groups. NOX4, MMP2 and 9 levels in group-2 were higher than in the other groups. MMP-9 levels in group-5 were lower than in groups 3 and 4 (<em>p</em> <!-->=<!--> <!-->.001). The level of 8-OHdG in groups 2 and 3 was higher than in the other groups (<em>p</em> <!-->=<!--> <!-->.001). In correlation analysis, 8-OHdG, MMP2, and 9 levels were negatively correlated with total thiol, whereas NOX4 and 8-OHdG levels were positively correlated with MMPs values.</p></div><div><h3>Conclusions</h3><p>The combination of testosterone with PDE-5 inhibitor suppresses MMP-9 levels and increases total thiol levels better than testosterone alone and tadalafil alone. Therefore, testosterone can be considered for use with PDE-5 inhibitor from the initial stage in case of testosterone deficiency.</p></div>","PeriodicalId":49129,"journal":{"name":"Revista Internacional De Andrologia","volume":"20 2","pages":"Pages 73-79"},"PeriodicalIF":0.8000,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The synergistic effects of testosterone and phophodiesterase-5 inhibitor combination on oxidative stress markers, matrix metalloproteinases and oxidative DNA damage: A randomized controlled experimental study\",\"authors\":\"Rahmi Aslan , Kerem Taken , Akif Erbin , Hamit Hakan Alp , Recep Eryilmaz , Omer Sarilar , Zubeyir Huyut\",\"doi\":\"10.1016/j.androl.2020.10.011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><p>To investigate the effects of combined tadalafil and testosterone usage on oxidative stress, DNA damage and MMPs in testosterone deficiency.</p></div><div><h3>Methods</h3><p>Fifty rats were randomly divided into 5 groups (<em>group-1:</em> sham group-placebo, g<em>roup-2:</em> bilateral orchiectomy (ORX), g<em>roup-3</em>: bilateral ORX<!--> <!-->+<!--> <!-->tadalafil, g<em>roup-4</em>: bilateral ORX<!--> <!-->+<!--> <!-->testosterone, g<em>roup-5</em>: bilateral ORX<!--> <!-->+<!--> <!-->tadalafil<!--> <!-->+<!--> <!-->testosterone). Group-3 received tadalafil (5<!--> <!-->mg/kg/day, oral). Group-4 was administered testosterone undecanoate (100<!--> <!-->mg/kg i.m., single dose). Group-5 was administered a combination of <em>tadalafil</em> and testosterone undecanoate. <em>All groups were compared</em> with regard to <em>serum</em> nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX-4), total thiol, matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels.</p></div><div><h3>Results</h3><p>Total thiol levels of group-2 were significantly lower than the other groups and thiol levels were higher in group-1 and group-5 than in the other groups. NOX4, MMP2 and 9 levels in group-2 were higher than in the other groups. MMP-9 levels in group-5 were lower than in groups 3 and 4 (<em>p</em> <!-->=<!--> <!-->.001). The level of 8-OHdG in groups 2 and 3 was higher than in the other groups (<em>p</em> <!-->=<!--> <!-->.001). In correlation analysis, 8-OHdG, MMP2, and 9 levels were negatively correlated with total thiol, whereas NOX4 and 8-OHdG levels were positively correlated with MMPs values.</p></div><div><h3>Conclusions</h3><p>The combination of testosterone with PDE-5 inhibitor suppresses MMP-9 levels and increases total thiol levels better than testosterone alone and tadalafil alone. Therefore, testosterone can be considered for use with PDE-5 inhibitor from the initial stage in case of testosterone deficiency.</p></div>\",\"PeriodicalId\":49129,\"journal\":{\"name\":\"Revista Internacional De Andrologia\",\"volume\":\"20 2\",\"pages\":\"Pages 73-79\"},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2022-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Revista Internacional De Andrologia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1698031X22000097\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"ANDROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Revista Internacional De Andrologia","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1698031X22000097","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ANDROLOGY","Score":null,"Total":0}
The synergistic effects of testosterone and phophodiesterase-5 inhibitor combination on oxidative stress markers, matrix metalloproteinases and oxidative DNA damage: A randomized controlled experimental study
Purpose
To investigate the effects of combined tadalafil and testosterone usage on oxidative stress, DNA damage and MMPs in testosterone deficiency.
Methods
Fifty rats were randomly divided into 5 groups (group-1: sham group-placebo, group-2: bilateral orchiectomy (ORX), group-3: bilateral ORX + tadalafil, group-4: bilateral ORX + testosterone, group-5: bilateral ORX + tadalafil + testosterone). Group-3 received tadalafil (5 mg/kg/day, oral). Group-4 was administered testosterone undecanoate (100 mg/kg i.m., single dose). Group-5 was administered a combination of tadalafil and testosterone undecanoate. All groups were compared with regard to serum nicotinamide adenine dinucleotide phosphate oxidase-4 (NOX-4), total thiol, matrix metalloproteinase-2 (MMP-2), MMP-3 and MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels.
Results
Total thiol levels of group-2 were significantly lower than the other groups and thiol levels were higher in group-1 and group-5 than in the other groups. NOX4, MMP2 and 9 levels in group-2 were higher than in the other groups. MMP-9 levels in group-5 were lower than in groups 3 and 4 (p = .001). The level of 8-OHdG in groups 2 and 3 was higher than in the other groups (p = .001). In correlation analysis, 8-OHdG, MMP2, and 9 levels were negatively correlated with total thiol, whereas NOX4 and 8-OHdG levels were positively correlated with MMPs values.
Conclusions
The combination of testosterone with PDE-5 inhibitor suppresses MMP-9 levels and increases total thiol levels better than testosterone alone and tadalafil alone. Therefore, testosterone can be considered for use with PDE-5 inhibitor from the initial stage in case of testosterone deficiency.
期刊介绍：
Revista Internacional de Andrología es la revista oficial de la Asociación Española de Andrología, Medicina Sexual y Reproductiva (ASESA), la Sociedade Portuguesa de Ardrologia, la Sociedad Argentina de Andrología (SAA), la Asociación Iberoamericana de Sociedades de Andrología (ANDRO), y la Federación Española de Sociedades de Sexología.
La revista publicada trimestralmente es revisada por pares y es líder en el la especialidad y en español y portugués. Recientemente también publica artículos en inglés.
El objetivo de la revista es principalmente la promoción del conocimiento y la educación médica continua, con un enfoque especial en el público español y latinoamericano, a través de la publicación de las contribuciones importantes de la investigación en el campo. Todos los miembros de las sociedades antes mencionadas reciben la revista y otros suscriptores individuales e institucionales de España, Portugal y América Latina.
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