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Yavaş Salımlı Hidrojen Sülfür (H2S) Donörü GYY4137'nin In Vitro İskemi-Reperfüzyon Modelinde Vasküler Düz Kas ve Endotel Cevabı Üzerine Etkisinin ve Etki Mekanizmasının Değerlendirilmesi

Emre Aydingoz, Selda; TEIMOORI, Ariyan; ORHAN, Halit Güner; ZEYNALOVA, Nargiz; DEMİRTAŞ, Elif; EFE, Oğuzhan Ekin; ÖZTURAN ÖZER, Huriye Eda


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    "creators": [
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        "affiliation": "Ba\u015fkent \u00dcniversitesi T\u0131p Fak\u00fcltesi T\u0131bbi Farmakoloji Anabilim Dal\u0131", 
        "name": "Emre Aydingoz, Selda"
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        "affiliation": "Ba\u015fkent \u00dcniversitesi T\u0131p Fak\u00fcltesi T\u0131bbi Farmakoloji Anabilim Dal\u0131", 
        "name": "TEIMOORI, Ariyan"
      }, 
      {
        "affiliation": "Ba\u015fkent \u00dcniversitesi T\u0131p Fak\u00fcltesi T\u0131bbi Farmakoloji Anabilim Dal\u0131", 
        "name": "ORHAN, Halit G\u00fcner"
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        "affiliation": "Ba\u015fkent \u00dcniversitesi T\u0131p Fak\u00fcltesi T\u0131bbi Farmakoloji Anabilim Dal\u0131", 
        "name": "ZEYNALOVA, Nargiz"
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      {
        "affiliation": "Ba\u015fkent \u00dcniversitesi T\u0131p Fak\u00fcltesi T\u0131bbi Farmakoloji Anabilim Dal\u0131", 
        "name": "DEM\u0130RTA\u015e, Elif"
      }, 
      {
        "affiliation": "Ba\u015fkent \u00dcniversitesi T\u0131p Fak\u00fcltesi T\u0131bbi Farmakoloji Anabilim Dal\u0131", 
        "name": "EFE, O\u011fuzhan Ekin"
      }, 
      {
        "affiliation": "Ba\u015fkent \u00dcniversitesi T\u0131p Fak\u00fcltesi Biyokimya Anabilim Dal\u0131", 
        "name": "\u00d6ZTURAN \u00d6ZER, Huriye Eda"
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    ], 
    "description": "<p>Koroner arter bypass cerrahisi s\u0131ras\u0131nda kullan\u0131lan otolog vask&uuml;ler greftlerin iskemi-reperf&uuml;zyon (\u0130R) hasar\u0131, cerrahi ba\u015far\u0131y\u0131 olumsuz etkileyebilmektedir. Bu &ccedil;al\u0131\u015fmada, yava\u015f sal\u0131nan bir hidrojen s&uuml;lf&uuml;r (H<sub>2</sub>S) don&ouml;r&uuml; olan GYY4137&#39;nin in vitro s\u0131&ccedil;an \u0130R hasar\u0131 modelinde vask&uuml;ler doku &uuml;zerindeki koruyucu etkileri ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r. Bu &ccedil;al\u0131\u015fma Ba\u015fkent &Uuml;niversitesi Hayvan Deneyleri Yerel Etik Kurulu taraf\u0131ndan onaylanm\u0131\u015ft\u0131r (Proje no: DA23/26, Karar no: 22/15, Tarih: 21/04/2022). Yirmi erkek (21-22 ay, 378,2 &plusmn; 10,19 g) Sprague-Dawley s\u0131&ccedil;an\u0131n torasik aortas\u0131 4&rsquo;e b&ouml;l&uuml;nerek deney gruplar\u0131na randomize edilmi\u015ftir: Kontrol, \u0130R, \u0130R + GYY4137 100 &micro;M, \u0130R + GYY4137 300 &micro;M. \u0130R modeli i&ccedil;in aort halkas\u0131 azot ile gazland\u0131r\u0131lm\u0131\u015f %0,9 salinde 4&deg;C&rsquo;de 24 saat bekletilip, 37&deg;C&rsquo;de Krebs-Henseleit sol&uuml;syonu i&ccedil;eren, %95 O<sub>2</sub>+%5 CO<sub>2</sub> ile gazland\u0131r\u0131lan organ banyosuna al\u0131narak 30 dk sodyum hipoklorite (200 &mu;M) maruz b\u0131rak\u0131lm\u0131\u015ft\u0131r. GYY4137 gruplar\u0131nda salin i&ccedil;ine GYY4137 eklenmi\u015ftir. Vask&uuml;ler fonksiyon organ banyosu d&uuml;zene\u011finde de\u011ferlendirilmi\u015f, doku malondialdehidi glutatyon ve kaspaz-3 aktivitesi biyokimyasal olarak &ouml;l&ccedil;&uuml;lm&uuml;\u015ft&uuml;r. \u0130R hasar\u0131 dokunun KCl (80 mM) yan\u0131t\u0131n\u0131 azaltm\u0131\u015f (Kontrol 1815 &plusmn; 140 mg, \u0130R 842 &plusmn; 160 mg, p = 0,0003), fenilefrin konsantrasyon-cevap e\u011frisinde E<sub>maks</sub>&rsquo;\u0131 art\u0131rm\u0131\u015f (Kontrol %144,1 &plusmn; %2,64, \u0130R %202,3 &plusmn; %4,9, p &lt; 0,0001), asetilkolin e\u011frisinde E<sub>maks&rsquo;\u0131 </sub>(Kontrol %78,4 &plusmn; %1,4, \u0130R %32,6 &plusmn; 3,4, p &lt; 0,0001) ve pD<sub>2</sub>&rsquo;yi d&uuml;\u015f&uuml;rm&uuml;\u015f (Kontrol 7,24 &plusmn; 0,05, \u0130R 5,18 &plusmn; 0,17, p &lt; 0,0001), sodyum nitroprusit e\u011frisinde ise E<sub>maks</sub>&rsquo;\u0131 art\u0131r\u0131rken (Kontrol %101,4 &plusmn; %1,47, \u0130R %113,6 &plusmn; %2,3, p = 0,0009), pD<sub>2</sub>&rsquo;yi azaltm\u0131\u015ft\u0131r (Kontrol 8,4 &plusmn; 0,03, \u0130R 8,23 &plusmn; 0,04, p = 0,00025). GYY4137, \u0130R&rsquo;ye ba\u011fl\u0131 bu fonksiyonel de\u011fi\u015fiklikleri d&uuml;zeltmemi\u015ftir. Di\u011fer taraftan, biyokimyasal analizlerde \u0130R ile artan malondialdehid seviyesi (Kontrol 8,4 &plusmn; 0,9 nmol/g, \u0130R 12,6 &plusmn; 1,0 nmol/g, p = 0,02), 100 &mu;M ve 300 &mu;M GYY4137 ile kontrol d&uuml;zeyine gerilemi\u015ftir (s\u0131ras\u0131yla 8,7 &plusmn; 0,9 nmol/g, p = 0,008 ve 7,6 &plusmn; 1,1 nmol/g, p = 0,012). Azalan glutatyon seviyesi (Kontrol 785 &plusmn; 61 nmol/g, \u0130R 506 &plusmn; 45 nmol/g, p = 0,012) 300 &mu;M GYY4137 varl\u0131\u011f\u0131nda normale d&ouml;nm&uuml;\u015f (709 &plusmn; 45 nmol/g, p = 0,004); artan doku kaspaz-3 seviyesi (Kontrol 2,4 &plusmn; 1,3 ng/g, \u0130R 8,4 &plusmn; 1,2 ng/g, p = 0,02), 100 &mu;M ve 300 &mu;M GYY4137 ile d&uuml;zelmi\u015ftir (s\u0131ras\u0131yla 2,3 &plusmn; 1,3 ng/g, p = 0,004 ve 3,2 &plusmn; 1,1 ng/g, p = 0,02). Bu bulgular, GYY4137&#39;nin \u0130R hasar\u0131n\u0131 takiben olu\u015fan oksidatif stres ve apoptoza kar\u015f\u0131 h&uuml;cresel koruma sa\u011flad\u0131\u011f\u0131n\u0131, ancak vask&uuml;ler disfonksiyonu &ouml;nemli &ouml;l&ccedil;&uuml;de iyile\u015ftirmedi\u011fini g&ouml;stermektedir. \u0130leri &ccedil;al\u0131\u015fmalar, sunulan bulgular\u0131n mekanizmalar\u0131n\u0131n anla\u015f\u0131lmas\u0131na ve \u0130R hasar\u0131na kar\u015f\u0131 potansiyel &ouml;nleme ve tedavi stratejileri geli\u015ftirilmesine odaklanmal\u0131d\u0131r.</p>", 
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      "GYY4137; izole organ banyo; s\u0131\u00e7an; in vitro; iskemi-reperf\u00fczyon"
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    "title": "Yava\u015f Sal\u0131ml\u0131 Hidrojen S\u00fclf\u00fcr (H2S) Don\u00f6r\u00fc GYY4137'nin  In Vitro \u0130skemi-Reperf\u00fczyon Modelinde Vask\u00fcler D\u00fcz Kas ve Endotel Cevab\u0131 \u00dczerine Etkisinin ve Etki Mekanizmas\u0131n\u0131n De\u011ferlendirilmesi", 
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