{"id":736,"date":"2018-01-30T16:00:52","date_gmt":"2018-01-30T13:00:52","guid":{"rendered":"https:\/\/tatd.org.tr\/tatdtoks\/2021\/09\/17\/sentetik-kannabinoid-zehirlenmesinde-albumin-tedavisi-hakkinda-ongoruler\/"},"modified":"2021-11-10T22:35:23","modified_gmt":"2021-11-10T19:35:23","slug":"sentetik-kannabinoid-zehirlenmesinde-albumin-tedavisi-hakkinda-ongoruler","status":"publish","type":"post","link":"https:\/\/tatd.org.tr\/toksikoloji\/2018\/01\/30\/sentetik-kannabinoid-zehirlenmesinde-albumin-tedavisi-hakkinda-ongoruler\/","title":{"rendered":"Sentetik Kannabinoid Zehirlenmesinde Albumin tedavisi hakk\u0131nda \u00d6ng\u00f6r\u00fcler"},"content":{"rendered":"

In silico<\/em>\u00a0g\u00f6zlemsel y\u00f6ntemler ila\u00e7lara ait farmakokinetik ve farmakodinamik hareketleri bilgisayar arac\u0131l\u0131kl\u0131 model sim\u00fclasyon programlar ile inceleyebilir. Bunlardan en bilinen biri olan AutoDock Vina \u015febekesi ile \u00a0bu ara\u015ft\u0131rmalar yap\u0131lmaktad\u0131r. Bu sanal programda \u00a0FDA taraf\u0131ndan onayl\u0131 olacak \u015fekilde kullan\u0131mdaki 1400 ilac\u0131n \u00a0farmakokinetik ve farmakodinamik hareketleri\u00a0 incelenebilmektedir. DockingApp olarak isim verilen eri\u015fime a\u00e7\u0131k, tamamen\u00a0 \u201cuser-friendly\u201d olan aplikasyon program\u0131 AutoDock Vina \u015febekesini kullanarak sim\u00fclasyonlar ve sanal tarama i\u015flemleri yaparak kannabinoidlerin hareketleri simule edilmi\u015ftir.\u00a0 (Bu konuda \u201cJournal of Computer Aided Molecular Design\u201d dergisinde yap\u0131lan makaleler sizlere de ilgin\u00e7 gelecek).<\/p>\n

\"\"<\/p>\n

\u015eekil 1.<\/strong> \u0130nsan Serum Alb\u00fcmin yap\u0131s\u0131. FA olarak g\u00f6sterilen b\u00f6lgeler Serbest Ya\u011f asidi ba\u011flama alanlar\u0131d\u0131r. Trp214 di\u011fer ba\u011flama b\u00f6lgesi.<\/p>\n

\"\"<\/p>\n

\u015eekil 2.<\/strong> \u0130nsan Serum Alb\u00fcminde ba\u011flanm\u0131\u015f olan \u0394-9-tetrahydrocannabinol (MAV\u0130 renkte ortada) molek\u00fcl\u00fc. Bu \u015fekil Autodock 4.0 ve \u201cgraphical user interface AutoDockTools\u201d kullanarak yap\u0131lm\u0131\u015ft\u0131r. K\u0131saltmalar ile g\u00f6sterilen amino asit ba\u011flanma b\u00f6lgeleridir.<\/p>\n

\u0130SA ile bu\u00a0 yaz\u0131l\u0131m ile yap\u0131lan \u00e7al\u0131\u015fmalarda\u00a0\u00a0 al\u0131nan sonu\u00e7lara g\u00f6re \u00a0\u0130SA\u2019in h\u0131zl\u0131ca ba\u011flad\u0131\u011f\u0131 kannabinoid maddeler:<\/p>\n

    \n
  1. \u0130ndirekt kannabinoid agonistleri olan\u00a0 URB597, AM5206, JZL184, JZL195\u00a0 ve \u00a0AM404;<\/li>\n
  2. Direkt kannabinoid agonistleri olan \u00a0WIN55,212-2 ve \u00a0CP55,940<\/li>\n
  3. Prototip \u00a0kannabinoid antagonisti veya invers \u00a0agonisti olan \u00a0SR141716<\/li>\n<\/ol>\n

    Kannabinoid ila\u00e7lar\u0131n \u0130SA\u2019 e ba\u011flanmas\u0131 i\u00e7in gereken serbest enerji \u22125.4 kcal\/mol ile \u00a0\u221210.9 kcal\/mol aras\u0131nda de\u011fi\u015fmektedir. Asl\u0131nda bu rakamlar \u0130SA:Kannabinoid kompleksi olu\u015fturmak i\u00e7in gerekli serbest enerjinin in vivo<\/em>\u00a0ortamda m\u00fcmk\u00fcn oldu\u011funu g\u00f6stermektedir. \u0130SA kannabinoidlerin v\u00fccuttaki etkilerini belirleyen ana transport molek\u00fcl\u00fc olarak ortaya \u00e7\u0131k\u0131yor ve kannabinoidlerin v\u00fccuttaki toksitelerinin tedavisi i\u00e7in de gelecekte \u0130SA\u2019 den faydalanaca\u011f\u0131z gibi g\u00f6r\u00fcn\u00fcyor.<\/p>\n

    Ancak burada Alb\u00fcmin molek\u00fcl\u00fcn\u00fcn \u015fu anda klinikte kulland\u0131\u011f\u0131m\u0131z suspansiyondan \u00a0farkl\u0131 olarak nanoteknoloji \u00fcr\u00fcn\u00fc olaca\u011f\u0131n\u0131 da s\u00f6ylemek gerekir. Literat\u00fcrde \u0130SA nanopartik\u00fclleri ile yap\u0131lan pek \u00e7ok \u00e7al\u0131\u015fma mevcut. \u00d6zellikle Klinik Toksikoloji konusunda dikkati \u00e7eken pop\u00fcler konular kanser hastalar\u0131nda kullan\u0131lan kemoterap\u00f6tik ajanlar\u0131n\u00a0 toksitesinde \u0130SA nanopartik\u00fcllerinin kullan\u0131m\u0131 ve bu ila\u00e7lar\u0131n yan etkilerinin azalt\u0131lmas\u0131 ile ilgili. \u0130SA nanopartik\u00fcllerinin \u00fcst\u00fcn \u00f6zellikleri olan ila\u00e7 ba\u011flama kapasitesinin y\u00fcksek olmas\u0131, kargo molek\u00fclleri degrade olmadan korumas\u0131,\u00a0 ilac\u0131n erirlili\u011fini ve biyoyararlan\u0131m\u0131n\u0131 art\u0131rmas\u0131, h\u00fccresel al\u0131m\u0131 \u00a0art\u0131rmas\u0131 ve en \u00f6nemlisi non- immun yap\u0131da olmas\u0131 bu molek\u00fclleri sanki s\u00fcper Toksikoloji sava\u015f\u00e7\u0131s\u0131 yapacak gibi g\u00f6r\u00fcn\u00fcyor.<\/p>\n

    Lipid kompartmanlarda \u00a0da\u011f\u0131l\u0131m\u0131 a\u00e7\u0131s\u0131ndan \u015fu anda intraven\u00f6z lipid sol\u00fcsyonlar\u0131n\u0131 sentetik kannabinoid t\u00fcrevi ila\u00e7lar\u0131n intoksikasyonlar\u0131nda\u00a0 kullanmak d\u0131\u015f\u0131nda pek alternatifimiz mevcut de\u011fil. Ancak \u0130SA nanopartik\u00fclleri daha yayg\u0131n ve ucuz oldu\u011fu zaman bu grup suistimal ila\u00e7lar\u0131na kar\u015f\u0131 en \u00f6nemli silah\u0131m\u0131z olacaklar.<\/p>\n

    Kaynaklar<\/h2>\n
      \n
    1. Leboffe L, \u00a0di Masi A,\u00a0 \u00a0Trezza V, \u00a0Polticelli F, \u00a0Ascenzi P. Human serum \u0130SA: A modulator of cannabinoid drugs. IUBMB Life, 69(11):834\u2013840, 2017<\/li>\n
    2. Bhushana B , Khanadeev V, Khlebtsovc B, Khlebtsovc N, Gopinath P. Impact of \u0130SA based approaches in nanomedicine: Imaging, targeting and drug delivery Advances in Colloid and Interface Science 246: 13\u201339, 2017<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

      \u0130nsan v\u00fccudunda endojen kannabinoid sistem geni\u015f bir yelpazede biyolojik olaylar\u0131 etkiler ve t\u00fcm memeli sistemlerinde homeostaz\u0131 sa\u011flar. Ge\u00e7mi\u015f y\u0131llarda yap\u0131lan pek \u00e7ok \u00e7al\u0131\u015fmalarda bu sistemdeki n\u00f6rotransmisyonu a\u00e7\u0131klamak i\u00e7in incelemeler yap\u0131lm\u0131\u015f\u00a0 ve direkt ve \u00a0indirekt kannabinoid agonistleri ile kannabinoid antagonistleri \u00e7al\u0131\u015f\u0131lm\u0131\u015ft\u0131r. Bilindi\u011fi \u00fczere kannabinoid agonistleri ve antagonistleri hidrofob yap\u0131da olduklar\u0131 i\u00e7in lipid dokuda da\u011f\u0131lmay\u0131 tercih ederler. V\u00fccut s\u0131v\u0131lar\u0131nda kannabinoid agonist ve antagonistlerin ta\u015f\u0131nmas\u0131 i\u00e7in \u00f6zel bir transporter ihtiyac\u0131 vard\u0131r. Burada en \u00f6nemli ta\u015f\u0131y\u0131c\u0131 molek\u00fcl \u0130nsan Serum Alb\u00fcmin (\u0130SA) dir. \u0130SA hem \u00a0endocannabinoid anandamid\u00a0 maddesini\u00a0 hem de \u0394-9-tetrahydrocannabinol (Esrar)\u0131 ba\u011flamaktad\u0131r. Yani kannabinoid ila\u00e7lar i\u00e7in \u0130SA\u2019 in en \u00f6nemli ta\u015f\u0131y\u0131c\u0131 oldu\u011fu varsay\u0131labilir.<\/p>\n","protected":false},"author":1538,"featured_media":1642,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[10014],"tags":[44,217,387],"class_list":["post-736","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-akademik-blog-yazisi","tag-albumin","tag-kannabinoid-zehirlenmesi","tag-tedavi"],"acf":[],"_links":{"self":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/736","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/users\/1538"}],"replies":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/comments?post=736"}],"version-history":[{"count":0,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/736\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media\/1642"}],"wp:attachment":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media?parent=736"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/categories?post=736"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/tags?post=736"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}