{"id":1137,"date":"2021-06-08T20:38:52","date_gmt":"2021-06-08T17:38:52","guid":{"rendered":"https:\/\/tatd.org.tr\/tatdtoks\/2021\/09\/17\/kadmiyum-kaynaklari-ve-toksisite\/"},"modified":"2022-03-23T00:34:19","modified_gmt":"2022-03-22T21:34:19","slug":"kadmiyum-kaynaklari-ve-toksisite","status":"publish","type":"post","link":"https:\/\/tatd.org.tr\/toksikoloji\/2021\/06\/08\/kadmiyum-kaynaklari-ve-toksisite\/","title":{"rendered":"Kadmiyum Kaynaklar\u0131 ve Toksisite"},"content":{"rendered":"

<\/h3>\n

Toxics dergisinin May\u0131s 2019 say\u0131s\u0131nda yay\u0131nlanan; Soisungwan Satarug\u2019un, bir kapsaml\u0131 inceleme [1], \u00fc\u00e7 epidemiyolojik ara\u015ft\u0131rma [2-4] ve be\u015f laboratuvar tabanl\u0131 ara\u015ft\u0131rmay\u0131 [5-9] ele ald\u0131\u011f\u0131 yaz\u0131s\u0131 \u00fczerinden, kadmiyum (Cd) kaynaklar\u0131 ve toksisitesini sizlerle tart\u0131\u015fmak iste\u011findeyim.<\/em><\/p>\n

Satarug\u2019un 2018 y\u0131l\u0131nda yapt\u0131\u011f\u0131 incelemede Cd’ye \u00e7evresel maruziyet ve bunun kronik b\u00f6brek hastal\u0131\u011f\u0131 ile ili\u015fkisi \u00f6ne \u00e7\u0131karken; Cd’nin pirin\u00e7, patates, bu\u011fday, ye\u015fil yaprakl\u0131 sebzeler ve di\u011fer tah\u0131llar gibi hemen t\u00fcm g\u0131da maddelerinde bulundu\u011funu g\u00f6steren diyet \u00e7al\u0131\u015fmalar\u0131n\u0131n verileri payla\u015f\u0131lm\u0131\u015f [1]. Karaci\u011fer ve b\u00f6brekte biriken Cd miktar\u0131n\u0131n belirlenmesinde oral al\u0131m, \u00fcriner e\u015fik ve at\u0131l\u0131m\u0131n birlikte de\u011ferlendirilmesi gereklili\u011fi vurgulanm\u0131\u015ft\u0131r.<\/p>\n

B\u00f6brek fonksiyonlar\u0131na etkisi hakk\u0131nda, t\u00fcb\u00fcler disfonksiyon g\u00f6steren \u03b22 mikroglubulinin (\u03b22MG) at\u0131l\u0131m\u0131 artm\u0131\u015f olan hastalarda d\u00fc\u015f\u00fck eGFR (<60 mL\/dak\/1.73 m2) izlenmi\u015f ve bu durum artm\u0131\u015f kronik b\u00f6brek hastal\u0131\u011f\u0131 riski ile ili\u015fkilendirilmi\u015ftir [2]. Bulgular tubuler patolojinin nefron atrofisine ve GFR d\u00fc\u015f\u00fc\u015f\u00fcne sebep oldu\u011funu d\u00fc\u015f\u00fcnd\u00fcrmektedir [10]. Yine protein\u00fcri ve glikoz\u00fcri gibi Cd ile ili\u015fkili b\u00f6brek patolojilerinin belirtileri olan kad\u0131nlarda kanser nedenli \u00f6l\u00fcmlerde 1.49-kat art\u0131\u015f g\u00f6zlenmi\u015f. Spesifik olarak uterus, b\u00f6brek, \u00fcretral kanserler s\u0131k g\u00f6r\u00fclm\u00fc\u015ft\u00fcr [3].<\/p>\n

D\u00fc\u015f\u00fck, orta veya y\u00fcksek seviyelerde \u00e7evresel Cd maruziyetinde menapoza girme ya\u015f\u0131 a\u00e7\u0131s\u0131ndan fark g\u00f6r\u00fclmezken;13 ya\u015f\u0131ndan \u00f6nce menar\u015f ihtimali, orta maruziyet i\u00e7in 1.3 ve y\u00fcksek maruziyet i\u00e7in ise 3.7-kat artm\u0131\u015ft\u0131r [4]. Bu bulgu, Cd verilen s\u0131\u00e7anlarda erken puberte g\u00f6r\u00fclmesiyle paralellik g\u00f6stermekte [11] olup Cd\u2019nin \u00f6strojenik aktiviteye sahip oldu\u011funu d\u00fc\u015f\u00fcnd\u00fcrmektedir.<\/p>\n

Cd inhalasyonunun geli\u015fmekte olan b\u00f6breklere etkisi incelenmi\u015f [5]; bu ama\u00e7la gestasyonun 8. ve 20. g\u00fcnleri aras\u0131ndaki gebe s\u0131\u00e7anlara g\u00fcnde 2 saat CdCl2<\/sub> aerosol (17.43 mg\/m3<\/sup>) inhale ettirilmi\u015f. Gestasyonun 21. g\u00fcn\u00fcnde fetuslar\u0131n b\u00f6breklerinde DNA ba\u011flay\u0131c\u0131 aktivite ve hipoksiyle-ind\u00fcklenebilir-fakt\u00f6r-1 (HIF-1) incelenmi\u015ftir. HIF-1 oksijen kullan\u0131m\u0131n\u0131n reg\u00fclasyonunda; h\u00fccrenin b\u00fcy\u00fcme, geli\u015fme ve ya\u015fam\u0131n\u0131 s\u00fcrd\u00fcrmesinde kritik bir role sahiptir. Toksik Cd maruziyeti olan annelerin fet\u00fcslerinin b\u00f6breklerinde DNA-ba\u011flay\u0131c\u0131 aktivitede hasarlanmayla birlikte HIF-1 ile reg\u00fcle edilen genlerden vask\u00fcler endotelyal b\u00fcy\u00fcme fakt\u00f6r\u00fcn\u00fcn (VEGF) transkript seviyesinde d\u00fc\u015f\u00fc\u015f g\u00f6zlemlenmi\u015ftir. Bu bulgular inhale Cd\u2019nin geli\u015fmekte olan b\u00f6breklerdeki potansiyel y\u0131k\u0131c\u0131 etkilerini ortaya koymaktad\u0131r.<\/p>\n

Cd\u2019nin mat\u00fcr b\u00f6breklerdeki etkisini ara\u015ft\u0131rmak i\u00e7in erkek Sprague-Dawley s\u0131\u00e7anlar\u0131na 12 hafta boyunca, haftada 5 g\u00fcn subkutan CdCl2<\/sub> (0.6 mg\/kg) uygulanm\u0131\u015f; sonras\u0131nda b\u00f6brek hasar\u0131n\u0131 g\u00f6steren \u00fcriner protein, KIM-1 ve \u03b22MG seviyeleri ind\u00fcklenmi\u015f ve s\u0131ras\u0131yla 2.2, 21.7 ve 6.1 kat artt\u0131\u011f\u0131 tespit edilmi\u015ftir. Ek olarak, b\u00f6brek korteksinde microRNA ekspresyonunun seviyesinde de de\u011fi\u015fiklik saptanm\u0131\u015ft\u0131r (44 miRNA seviyesi artm\u0131\u015f, 54 miRNA seviyesi azalm\u0131\u015f). Yani Cd sebepli b\u00f6brek hasar\u0131, s\u0131\u00e7an\u0131n b\u00f6brek korteksine disreg\u00fcle miRNA ekspresyonuyla e\u015f zamanl\u0131 geli\u015fmi\u015ftir. Bu bulgularla miRNA\u2019n\u0131n Cd-ili\u015fkili b\u00f6brek hasar\u0131 i\u00e7in bir g\u00f6sterge oldu\u011fu d\u00fc\u015f\u00fcn\u00fclebilir.<\/p>\n

Cd’nin periodontal kemik \u00fczerindeki etkilerini ara\u015ft\u0131rmak i\u00e7in yine erkek Sprague-Dawley s\u0131\u00e7anlar\u0131na 12 hafta boyunca haftada 5 g\u00fcn subkutan CdCl2<\/sub> (0.6 mg\/kg) enjeksiyonlar\u0131 yap\u0131lm\u0131\u015f [7]; semento-enamel bile\u015fke ile alveolar kemik krest aras\u0131ndaki mesafenin artt\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bu durum, Cd\u2019nin periodontal hastal\u0131\u011fa muhtemel katk\u0131s\u0131 olarak de\u011ferlendirilmi\u015f ve y\u00fcksek Cd seviyelerinin Amerikan toplumunda g\u00f6r\u00fclen periodontal hastal\u0131k geli\u015fme riskindeki art\u0131\u015f ile ili\u015fkili olabilece\u011fini d\u00fc\u015f\u00fcnd\u00fcrm\u00fc\u015ft\u00fcr.<\/p>\n

H\u00fccresel seviyede, mitokondri \u00fczerindeki etkileri INS-1 insan pankreas h\u00fccre hatt\u0131nda incelenmi\u015ftir [8]. H\u00fccre \u00f6l\u00fcm\u00fcne sebep olan Cd konsantrasyonunun 10 kat azalt\u0131lm\u0131\u015f hali, enerji y\u00fck\u00fc ve adenozin tri-fosfat (ATP) senteziyle de\u011ferlendirilen mitokondrial fonksiyon \u00fczerinde hi\u00e7 etki g\u00f6stermemi\u015ftir. Ancak fizyonun bir g\u00f6stergesi olarak, mitokondrinin d\u00fc\u015f\u00fck seviye Cd\u2019ye kar\u015f\u0131 uyum cevab\u0131 olarak de\u011ferlendirilen, mitokondriyal yuvarlakla\u015fmaya sebep olmu\u015ftur. H\u00fccresel Cd al\u0131m\u0131 artarsa, organel hasarlanmas\u0131 ile birlikte h\u00fccresel disfonksiyon ve h\u00fccre \u00f6l\u00fcm\u00fc g\u00f6r\u00fcl\u00fcr.<\/p>\n

Cd\u2019nin hiperinsulinemi, ins\u00fclin rezistans\u0131, adiposit disfonksiyonu ve hepatik ins\u00fclin duyarl\u0131l\u0131\u011f\u0131n\u0131n azalmas\u0131na sebep oldu\u011fu; ayr\u0131ca farkl\u0131 dokularda progresif trigliserid depolanmas\u0131na yol a\u00e7t\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Anti-diyabetik bir ila\u00e7 olan metforminin bu etkilere kar\u015f\u0131 terapotik \u00f6zelli\u011fi yine s\u0131\u00e7anlarda incelenmi\u015f ve Cd taraf\u0131ndan ind\u00fcklenen glikoz tolerans\u0131 ve lipid birikimi \u00fczerinde olduk\u00e7a s\u0131n\u0131rl\u0131 bir etkinlik g\u00f6stermi\u015ftir [9].<\/p>\n

\u00d6zet olarak, bu ara\u015ft\u0131rmalar Cd\u2019ye \u00e7evresel maruziyetin \u00f6zellikle kad\u0131nlarda kansere ba\u011fl\u0131 artm\u0131\u015f mortalite [3], erken menar\u015f [4] ve kronik b\u00f6brek hastal\u0131\u011f\u0131 [2] ile ili\u015fkilidir. \u0130nhale Cd’nin fet\u00fcslerde b\u00f6brek geli\u015fimi \u00fczerindeki potansiyel etkileri, hamile s\u0131\u00e7anlar\u0131n kullan\u0131ld\u0131\u011f\u0131 bir \u00e7al\u0131\u015fmada a\u00e7\u0131k\u00e7a g\u00f6r\u00fclm\u00fc\u015ft\u00fcr [5]. Sprague-Dawley s\u0131\u00e7anlar\u0131yla yap\u0131lan \u00e7al\u0131\u015fmalar, bir dizi miRNA’daki disreg\u00fclasyonun renal Cd toksisitesine arac\u0131l\u0131k etti\u011fini [6] ve Cd’nin periodontal hastal\u0131\u011fa katk\u0131da bulundu\u011funu [7] g\u00f6stermektedir. D\u00fc\u015f\u00fck doz Cd’nin insan pankreas h\u00fccrelerindeki mitokondri \u00fczerinde erken etkisi g\u00f6zlenmi\u015ftir [8]. Bununla birlikte, Cd ile ind\u00fcklenen metabolik d\u00fczensizliklerde metforminin terap\u00f6tik etkinli\u011fi g\u00f6sterilememi\u015ftir [9].<\/p>\n

Referanslar<\/strong><\/u><\/h2>\n

1. Satarug, S. Dietary cadmium intake and its effects on kidneys. Toxics 2018, 6, 15.<\/p>\n

2. Satarug, S.; Ruangyuttikarn, W.; Nishijo, M.; Ruiz, P. Urinary cadmium threshold to prevent kidney disease development. Toxics 2018, 6, 26.<\/p>\n

3. Nishijo, M.; Nakagawa, H.; Suwazono, Y.; Nogawa, K.; Sakurai, M.; Ishizaki, M.; Kido, T. Cancer mortality in residents of the cadmium-polluted Jinzu River Basin in Toyama, Japan. Toxics 2018, 6, 23.<\/p>\n

4. Chen, X.; Zhu, G.; Jin, T. Effects of cadmium exposure on age of menarche and menopause. Toxics 2017, 6, 6.<\/p>\n

5. Jacobo-Estrada, T.; Cardenas-Gonzalez, M.; Santoyo-S\u00e1nchez, M.P.; Thevenod, F.; Barbier, O. Intrauterine exposure to cadmium reduces HIF-1 DNA-binding ability in rat fetal kidneys. Toxics 2018, 6, 53.<\/p>\n

6. Fay, M.J.; Alt, L.A.C.; Ryba, D.; Salamah, R.; Peach, R.; Papaeliou, A.; Zawadzka, S.; Weiss, A.; Patel, N.; Rahman, A.; et al. Cadmium nephrotoxicity is associated with altered microRNA expression in the rat renal cortex. Toxics 2018, 6, 16.<\/p>\n

7. Browar, A.W.; Koufos, E.B.;Wei, Y.; Leavitt, L.L.; Prozialeck,W.C.; Edwards, J.R. Cadmium exposure disrupts periodontal bone in experimental animals: Implications for periodontal disease in humans. Toxics 2018, 6, 32.<\/p>\n

8. Jacquet, A.; Cottet-Rousselle, C.; Arnaud, J.; Julien Saint Amand, K.; Ben Messaoud, R.; L\u00e9non, M.; Demeilliers, C.; Moulis, J.M. Mitochondrial morphology and function of the pancreatic-cells INS-1 model upon chronic exposure to sub-lethal cadmium doses. Toxics 2018, 6, 20.<\/p>\n

9. Sarmiento-Ortega, V.E.; Brambila, E.; Flores-Hern\u00e1ndez, J.\u00c1.; D\u00edaz, A.; Pe\u00f1a-Rosas, U.; Moroni-Gonz\u00e1lez, D.; Aburto-Luna, V.; Trevi\u00f1o, S. The NOAEL Metformin d\u00f6\u015fe is ineffective against metabolic disruption induced by chronic cadmium exposure in Wistar rats. Toxics 2018, 6, 55.<\/p>\n

10. Schnaper, H.W. The tubulointerstitial pathophysiology of progressive kidney disease. Adv. Chron. Kidney Dis. 2017, 24, 107\u2013116.<\/p>\n

11. Johnson, M.D.; Kenney, N.; Stoica, A.; Hilakivi-Clarke, L.; Singh, B.; Chepko, G.; Clarke, R.; Sholler, P.F.; Lirio, A.A.; Foss, C.; et al. Cadmium mimics the in vivo e
\nects of estrogen in the uterus and mammary gland. Nat. Med. 2003, 9, 1081\u20131084.<\/p>\n","protected":false},"excerpt":{"rendered":"

Toxics dergisinin May\u0131s 2019 say\u0131s\u0131nda yay\u0131nlanan; Soisungwan Satarug\u2019un, bir kapsaml\u0131 inceleme [1], \u00fc\u00e7 epidemiyolojik ara\u015ft\u0131rma [2-4] ve be\u015f laboratuvar tabanl\u0131 ara\u015ft\u0131rmay\u0131 [5-9]…<\/p>\n","protected":false},"author":212,"featured_media":2067,"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":[10010,10014,10019],"tags":[208,209,210,413],"class_list":["post-1137","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-slider","category-akademik-blog-yazisi","category-tft","tag-kadmiyum","tag-kadmiyum-kaynaklari","tag-kadmiyum-toksisitesi","tag-toksisite"],"acf":[],"_links":{"self":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/1137","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\/212"}],"replies":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/comments?post=1137"}],"version-history":[{"count":0,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/1137\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media\/2067"}],"wp:attachment":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media?parent=1137"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/categories?post=1137"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/tags?post=1137"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}