Selma CIRRIK, Gulay HACIOĞLU, Emine Gülçeri GÜLEÇ PEKER, Hatıce KESER, Selcen ABIDIN

Yaşa bağlı oksidatif stres ve nitrik oksit azalışında 7,8-dihidroksiflavonun etkisi

Amaç: Beyin kaynaklı nörotrofik faktör (BDNF) reseptör agonisti olarak bilinen 7,8-dihidroksiflavon (7,8-DHF)’un antioksidan özelliklerinin yanı sıra, nitrik oksit (NO) üretimini de etkilediği bildirilmiştir. Yaşlı rodentlerde 7,8-DHF’nin merkezi sinir sisteminde olumlu etkileri gösterilmiş olsa da, nöral olmayan dokulardaki etkileri bilinmemektedir. Literatürde karaciğer, böbrek ve kalp dokularının yaşa bağlı oksidatif stres ve NO düzensizliği gösterdiği belirtilmiştir. Bu çalışmada 7,8-DHF'nin yaşlı farelerde karaciğer, böbrek ve kalp dokularında oksidatif stres ve NO üretimi üzerine etkileri araştırıldı.Gereç ve yöntem: Erkek C57BL/6 fareler; genç (5 aylık, n=10), yaşlı (18 aylık, n=10) ve DHF-yaşlı (n=7) olmak üzere 3 gruba ayrıldı. DHF-yaşlı grubundaki farelere 3 hafta boyunca 7,8-DHF (5 mg.kg-1.gün-1, intraperitoneal) uygulaması yapıldı. Farelerin karaciğer, kalp ve böbrek dokularında malondialdehid (MDA), redükte glutatyon (GSH) ve nitrit-nitrat (NOx) seviyeleri ölçüldü.Bulgular: Yaşlı grupta gözlenen hepatik MDA artışı (p<0,001) ve GSH azalışı (p<0,01), 7,8-DHF tedavisi ile önemli ölçüde değişti. Yaşlı grupta değişmeyen hepatik NOx seviyesi 7,8-DHF tedavisi ile yükseldi (p<0,001). 7,8-DHF tedavisi yaşa bağlı renal MDA artışını etkilemedi, ancak renal GSH (p<0,05) ve NOx (p<0,001) azalışlarını hafifletti. 7,8-DHF tedavisi kardiyak oksidatif stresi etkilemedi, ancak yaşa bağlı NOx azalışını hafifletti (p<0,001).Sonuç: 7,8-DHF karaciğer ve böbrek dokusunda yaşa bağlı oksidatif stres artışını, karaciğer, kalp ve böbrek dokusunda ise yaşa bağlı NO azalışını engellemede etkili olmuştur. Yaşlılıkta sinir sistemi dışındaki dokularda gözlenen fonksiyonel kayıpların engellenmesinde 7,8-DHF ümit verici bir bileşik olabilir. Bu bileşiğin tüm etkilerini ortaya koymak için yeni araştırmalara ihtiyaç vardır.

Anahtar Kelimeler:

Yaşlanma, oksidatif stres, Nox, 7, 8-dihidroksiflavon

The effect of 7,8-dihydroxyflavone on age related oxidative stress and nitric oxide depletion

Purpose: It has been reported that 7,8-dihydroxyflavone (7,8-DHF), known as a brain-derived neurotrophic factor (BDNF) receptor agonist, affects nitric oxide (NO) production as well as its antioxidant properties. Although favorable effects of 7,8-DHF have been reported in the central nervous system in aged rodents, its effects on non-neural tissues are not fully understood yet. In the literature, it has been stated that liver, kidney and heart tissues show age-related oxidative stress and NO dysregulation. In this study, the effects of 7,8-DHF on oxidative stress and NO production in liver, kidney and heart tissues in aged mice were investigated.Materials and methods: Male C57BL/6 mice were divided into 3 groups as young (5 months old, n=10), elderly (18 months old, n=10) and DHF-elderly (18 months old, n=7). The mice in DHF-elderly group were treated with 7,8-DHF (5 mg/kg-1.day-1, intraperitoneally) for 3 weeks. The malondialdehyde (MDA), reduced glutathione (GSH) and nitrite/nitrate (NOx) levels were measured in the liver, heart and kidney tissues of mice.Results: Hepatic MDA increase (p<0.001) and GSH decrease (p<0.01) observed in the elderly group were significantly reversed with 7,8-DHF treatment. Unchanged hepatic NOx level in the elderly group, increased with 7,8-DHF treatment (p<0.001). 7,8-DHF treatment did not affect the age-related increase in renal MDA, but attenuated the renal GSH (p<0.05) and NOx (p<0.001) decrements. 7,8-DHF treatment did not affect cardiac oxidative stress, but attenuated age-related NOx reduction (p<0.001).Conclusion: 7,8-DHF was effective in preventing age-related oxidative stress in hepatic and renal tissue, and age-related NO decrement in liver, heart and kidney. 7,8-DHF might be a promising compound in preventing age related functional loss in non-neural tissues. Further studies are needed to reveal all effects of this compound.

Keywords:

Aging, oxidative stress, NOx, 7, 8-dihydroxyflavone,

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