Deneysel diyabetik nefropatide quercetin'in renoprotektif potansiyeli: antiapoptotik ve antioksidan etkilerin değerlendirilmesi

Öz

Amaç: Sıçanlarda diyabetin neden olduğu böbrek hasarına katkıda bulunan apoptoz düzenleyici genlerin ekspresyonunu değerlendirerek güçlü bir biyoflavonoid olan quercetin'in renoprotektif ve antiapoptotik etkilerini araştırmak.

Yöntemler: Sıçanlar 4 gruba ayrıldı; Kontrol, STZ-diyabetik, STZ-diyabetik + Quercetin ve Quercetin kontrol. Açlık kan şekeri, vücut ağırlığı ve idrar mikroalbüminüri değerleri ölçüldü. İmmünohistokimya bax, bcl-2, kaspaz-3 antikorları kullanılarak gerçekleştirildi. Apoptoz tespiti için TUNEL yöntemi uygulandı. Homojenize böbrek dokularında ileri oksidasyon protein ürünleri (AOPP), protein karbonil oksidasyon (PCO), malondialdehid (MDA) ve süperoksit dismutaz (SOD) aktivitesi ölçüldü.

Bulgular: Tedavi edilmeyen diyabetik gruba kıyasla, quercetin uygulanan diyabetik grupta kan şekeri ve mikroalbüminüri düzeyleri anlamlı olarak azalmıştı (sırasıyla; p=0,020, p=0,003). MDA, AOPP ve PCO seviyeleri anlamlı olarak azaldı (sırasıyla; p=0,001, p=0,0001, p=0,0005), ancak SOD aktivitesinin quercetin uygulanan diyabetik grupta arttığı tespit edildi (p=0,005). Quercetin uygulanan diyabetiklerde, tedavi edilmemiş diyabetik gruba kıyasla bcl-2, bax ve kaspaz-3'ün immün boyanması azaldı.  Tedavi edilmeyen diyabetik grubun böbrek tübüllerinde apoptotik hücrelerde belirgin bir artış gözlenirken, quercetin uygulanan diyabetik grupta belirgin bir düşüş gözlendi (p=0,0001).

Sonuç: Antioksidan etkileri olan quercetin'in antiapoptotik etkilerinin, diyabetik komplikasyonların etkilerini azaltmada ve yeni komplikasyonları önlemede yararlı olabileceği sonucuna vardık.

Anahtar Kelimeler

• Deneysel diyabetik nefropati,Quercetin,böbrek,apoptoz,oksidatif stres

Renoprotective potential of quercetin in experimental diabetic nephropathy: assesing antiapoptotic and antioxidant effects

Abstract

Aim: We investigated renoprotective and anti-apoptotic effects of quercetin, a potent bioflavonoid, by evaluating expression of apoptosis-regulatory genes that contribute to the kidney damage caused by diabetes in rats.

Methods: Rats were divided into 4 groups; Control, STZ-induced diabetic, STZ-induced diabetic+Quercetin and Quercetin control. Values of fasting blood glucose, body weight and urine microalbuminuria measured. Immunohistochemistry was performed using bax, bcl-2, caspase-3 antibodies. For apoptosis detection, TUNEL method was applied. Advanced oxidation protein products (AOPP), protein carbonyl oxidation (PCO), malondialdehyde (MDA) and superoxide dismutase (SOD) activity were measured in homogenized kidney tissues.

Results: Blood glucose and microalbuminuria levels were significantly decreased in quercetin-treated diabetic group compared to the untreated-diabetic group (p=0.020 and p=0.003; respectively).  MDA, AOPP and PCO levels were significantly decreased (p=0.001, p=0.0001 and p=0.0005; respectively); however, SOD activity were found to increase in quercetin-treated diabetic group (p=0.005). Immunostaining of bcl-2, bax and caspase-3 was decreased compared to the untreated-diabetic group. Apoptotic cells especially increased in the kidney tubuli of untreated-diabetic group and on the contrary, a significant decrease was observed in the group that received a quercetin treatment (p=0.0001).

Conclusion: Our results revealed that antiapoptotic effects of quercetin, which has predominantly antioxidant effects, may be useful in reducing effects of diabetic complications and preventing new complications.                                                                 

Keywords

• Experimental diabetic nephropathy,Quercetin,kidney,apoptosis,oxidative stress

Kaynakça

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