Ağır Metal Miksinin İnsan Aort Vasküler Düz Kas Hücrelerinde Genotoksik ve Apoptotik Etkileri

Amaç: Ağır metaller özgül ağırlıkları 5g cm-3ten yüksek olan en yaygın kirleticilerdir. Insanların ağır metallere maruziyeti genellikle ağır metal içeren su ve besinlerin tüketilmesi yolu ile olmaktadır. Içme suyu yolu ile vücuda giren metaller genotoksisite ve çeşitli hastalıklara neden olurlar. Bu nedenle insani tüketim amaçlı kullanılan sularda ağır metallerin kabul edilebilir limitleri kanun ve yönetmelikler ile belirlenmiştir. Bizim çalışmamız içme suyunda izin verilen limitlerde metal miksinin (Cu, Zn, Pb ve Fe) insan aort düz kas hücrelerinde (TG-HA-VSMC) etkilerini moleküler düzeyde araştırmayı amaçlamıştır. Materyal-Metot: İnsan aort düz kas hücrelerine içme sularında izin verilen düzey ve 10 kat yüksek konsantrasyonda metal miksi 24 ve 48 saat süre ile uygulandı ve RAPD-DNA polimorfizmine ilaveten antioksidan enzimler (CuZn-SOD, Mn-SOD, CAT, GST), ısı şok proteinleri (HSP27, HSP60, HSP70), apoptoz yolak (p53, PUMA, BCL2, BAX, Cyt-C, Casp-3, TNF-α, Casp-8, DR4, DR5) hücre döngüsü kontrol (p21) DNA tamir (EXO1) gen ifadeleri belirlendi. Bulgular: Ağır metal uygulamasının DNA polimorfizminde, apoptotik hücre oranında, antioksidan ve apoptoz yolağı gen ifadelerinde artışa neden olduğu belirlendi. Sonuç: Sonuç olarak, içme sularında izin verilen limitlerde ağır metal karışımının aorta düz kas hücrelerinde oksidatif stres, genotoksisite ve apoptoza neden olduğu belirlendi. Vasküler düz kas hücrelerinde apoptozun arteroskleroz, hipertansiyon gibi hastalıkların patofizyolojisinde rol oynadığı göz önünde bulundurulduğunda bu limitlerin daha kapsamlı çalışmalarda araştırılarak değerlendirilmesi gerektiği düşünüldü.

Genotoxic and Apoptotic Effects of Heavy Metal Mixture on Human Aortic Vascular Smooth Muscle Cell Line

Objective: Heavy metals are the most common pollutantswith specific gravity greater than 5g cm-3. Human exposureto heavy metals occurs mostly through the consumption offood and water containing heavy metals. Metals that enter thebody via drinking water may cause genotoxicity and variousdiseases. Therefore, permissible limits of heavy metals inwater for human consumption have been determined by lawsand regulations. Our study aimed to investigate the effectsof a mix of metals (Cu, Zn, Pb and Fe) at permissible limitsin drinking water on aortic smooth muscle cells (TG-HAVSMC)with at molecular level.Material-Method: A metal mix at the permissible concentrationfor drinking water and 10-fold higher concentration wereexposed to human aortic smooth muscle for 24 and 48 hours, andgene expression of antioxidant enzymes (CuZn-SOD, Mn-SOD,CAT, GST), heat-shock proteins (HSP27, HSP60, HSP70) andapoptosis pathway (p53, PUMA, BCL2, BAX, Cyt-C, Casp-3,TNF-α, Casp-8, DR4, DR5) cell cycle control (p21) and DNArepair (EXO1) were investigated in addition to RAPD-DNApolymorphism.Results: It was determined that heavy metal exposure causedincrease in the DNA polymorphism, apoptotic cell ratios andenhanced antioxidant and apoptosis pathway gene expressionin cells.Conclusions: In conclusion, the mix consisting of heavy metalsat permissible limits in drinking water has been shown to causeoxidative stress, genotoxicity and apoptosis in human aorticsmooth muscle cells. Considering that apoptosis in vascularsmooth muscle cells plays a role in the pathophysiology ofdiseases such as arteriosclerosis and hypertension, we believeit would be beneficial to assess these limits through extensiveinvestigations in further studies.

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