Diyetsel takviye Spirulina'nın sitokrom p450 ve GST aracılı potansiyel ilaç etkileşimlerinin moleküler düzeyde aydınlatılması
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Tarih
2013
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Çanakkale Onsekiz Mart Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Spirulina doğal preparatı, fotosentetik mavi yeşil alg türü olan Spirulina platensis biyokütlesinden üretilen, zengin antioksidan özellikteki fitokimyasal ve besin içeriğinden dolayı halk arasında yaygın olarak tercih edilen bir üründür. Çalışmalar Spirulinanın farklı hastalıkların tedavisinde alternatif ve tamamlayıcı olarak kullanılmasına yönelik terapötik etkilerini ortaya koymuştur. Ancak, Spirulina?nın ilaç ve ksenobiyotiklerin büyük kısmının metabolizmasından sorumlu sitokrom P450 ve glutatyon S-transferaz (GST) enzimleri üzerine olan etkileri henüz aydınlatılmamıştır. Bu çalışmanın amacı; Spirulina doğal preparatının, ksenobiyotik metabolizmasında önemli rolü bulunan başlıca sitokrom P450 ve GST izozimleri üzerine etkilerinin moleküler düzeyde aydınlatılmasıdır. Bu amaçla, su içerisinde çözülen Spirulina 35 gün süreyle günlük 200, 500, 1000 mg/kg dozlarında oral olarak sıçanlara verilmiştir. Uygulama sonucunda, CYP1A2 ve CYP2E1?nin aktivite/ekspresyon düzeylerinde; mRNA için %14-%30, protein seviyesi için %19-%67, enzim aktiviteleri için %22-%45 arasında azalışlar görülmüştür (p<0.05). Spirulina uygulaması CYP3A1 mRNA ve protein seviyelerini kontrol grubuna kıyasla artırırken (p<0.05), enzim aktivitesinde küçük oranda anlamlı olmayan düşüşlere neden olmuştur. Gözlemlenen bu çift yönlü etki, Spirulina?nın içeriğindeki bazı aktif fitokimyasalların CYP3A1 enzimini inhibe ederek, mRNA ve protein indüksiyonu ile artan katalitik aktiviteyi kontrol grubuna benzer seviyelere çektiği ihtimalini düşündürmektedir. Bunlara ek olarak, Spirulina total GST aktivitesini 1. Doz grubunda kontrol grubuna kıyasla artırırken (%33, p<0.05), GST Mu ve GST Pi aktivitelerinde anlamlı bir değişiklik meydana getirmemiştir. Elde edilen verilere göre, Spirulina? nın karsinojen aktivasyonunda rol alan CYP1A2 ve CYP2E1?i inhibe etmesi, bu maddelerin karsinojenez, mutajenez ve toksisitelerinde potansiyel kemopreventif bir ajan olduğunu göstermektedir. Ayrıca, Spirulina?nın özellikle CYP1A2, CYP2E1 ve CYP3A1 tarafından metabolize edilen bazı klinik ilaçların farmakokinetiğinde potansiyel değişimler yaratabileceği düşünülmektedir. Anahtar Kelimeler: Spirulina, sitokrom P450, GST, ksenobiyotik metabolizması, ilaç etkileşimi, kemopreventif etki
Spirulina is a kind of photosynthetic blue green-algea having remarkable nutrient profile and antioxidant phytochemical constituents. Manufactured as dietary supplement, Spirulina has been widely used among people in the alternative and complementary therapies. Recent research studies demonstrated its therapeutic benefits towards a diverse array of disease conditions. However, the cytochrome P450s and GSTs mediated drug/chemical interaction potential of Spirulina has not been pursued yet. The aim of this study is to elucidate the effects of Spirulina on the main cytochrome P450 and GST isozymes. With this aim, Spirulina was given to the rats orally at doses of 200, 500, and 1000 mg/kg/bw daily for 35 consecutive days. Accordingly, the hepatic expression levels and enzymatic activities of CYP1A2 and CYP2E1 decreased significantly relative to controls. The decreases were changing between 14 to 30% for mRNA, 19 to 67% for protein levels and 22 to 45% for the enzyme activities (p<0.05). In terms of CYP3A1, while the Spirulina application resulted in significant increases at the protein and mRNA levels, these increases were not represented at the enzyme activities.This dual effect observed for CYP3A1 in SP treated rat liver i.e., induced mRNA/protein level, but the reduced/unchanged enzymatic activities suggest that enzyme inhibition caused by the constituents of SP may draw the catalytic activities to the values near to that of observed in controls. In case of GSTs, no remarkable effects on the activities of GST Mu and GST Pi isozyme were observed. In conclusion, the inhibitory effects of Spirulina on carcinogen activating CYP1A2 and CYP2E1 may indicate the potential of this compound as chemopreventive agent towards organ toxicities, mutagenesis and carcinogenesis induced by chemicals. Current data may also indicate that Spirulina has some potential to change the pharmacokinetics of clinical drugs especially metabolized by CYP1A2, CYP2E1 and CYP3A1. Key words: Spirulina, cytochrome P450, GST, xenobiotic metabolism, drug interaction, chemoprevention.
Spirulina is a kind of photosynthetic blue green-algea having remarkable nutrient profile and antioxidant phytochemical constituents. Manufactured as dietary supplement, Spirulina has been widely used among people in the alternative and complementary therapies. Recent research studies demonstrated its therapeutic benefits towards a diverse array of disease conditions. However, the cytochrome P450s and GSTs mediated drug/chemical interaction potential of Spirulina has not been pursued yet. The aim of this study is to elucidate the effects of Spirulina on the main cytochrome P450 and GST isozymes. With this aim, Spirulina was given to the rats orally at doses of 200, 500, and 1000 mg/kg/bw daily for 35 consecutive days. Accordingly, the hepatic expression levels and enzymatic activities of CYP1A2 and CYP2E1 decreased significantly relative to controls. The decreases were changing between 14 to 30% for mRNA, 19 to 67% for protein levels and 22 to 45% for the enzyme activities (p<0.05). In terms of CYP3A1, while the Spirulina application resulted in significant increases at the protein and mRNA levels, these increases were not represented at the enzyme activities.This dual effect observed for CYP3A1 in SP treated rat liver i.e., induced mRNA/protein level, but the reduced/unchanged enzymatic activities suggest that enzyme inhibition caused by the constituents of SP may draw the catalytic activities to the values near to that of observed in controls. In case of GSTs, no remarkable effects on the activities of GST Mu and GST Pi isozyme were observed. In conclusion, the inhibitory effects of Spirulina on carcinogen activating CYP1A2 and CYP2E1 may indicate the potential of this compound as chemopreventive agent towards organ toxicities, mutagenesis and carcinogenesis induced by chemicals. Current data may also indicate that Spirulina has some potential to change the pharmacokinetics of clinical drugs especially metabolized by CYP1A2, CYP2E1 and CYP3A1. Key words: Spirulina, cytochrome P450, GST, xenobiotic metabolism, drug interaction, chemoprevention.
Açıklama
Fen Bilimleri Enstitüsü, Biyoloji Ana Bilim Dalı
Anahtar Kelimeler
Biyokimya, Biochemistry, Biyoloji
