Streptozotosin ile indüklenmiş diyabetik rat modelinde kuersetinin HPA aksı ve depresyona etkisi
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Dosyalar
Tarih
2014
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Selçuk Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Flavonoid ailesinin en güçlü flavonollerinden biri olan kuersetinin sağlık açısından çeşitli faydaları gösterilmiştir. Depresyon fizyopatogenezinde söz edilen oksidatif stres, enflamasyon ve hipotalamik-hipofizer-adrenal aks disregülasyonu diyabetik komplikasyonlarla da ilişkilidir. Bu çalışmada yan etkiler ve tedavi uyumsuzluğu nedeniyle geleneksel antidepresan ilaç tedavilerinin sınırlı fayda sunduğu diyabette kuersetinin antidepresan benzeri karakteri ve hipotalamik-hipofizer-adrenal aks üzerine etkileri araştırılmıştır. Bu amaçla diyabetik ve non-diyabetik iki ana grupta; kontrol, 50 mg/kg ve 100 mg/kg i.p. kuersetin uygulanan üçer alt grup olacak şekilde toplam altı grupta 45 erişkin erkek sıçan kullanılmıştır. Tek doz streptozotosin (60 mg/kg) uygulamasından 72 saat sonra kan glukozu tayiniyle diyabet doğrulamasını takiben 21 gün süreyle kuersetin uygulamaları gerçekleştirilmiş ve haftalık ağırlık takibi yapılmıştır. 14. ve 21. günlerde kan glukozu ölçülmüştür. Porsolt testi amacıyla son uygulamadan bir gün önce 15 dakika süreyle aklimatizasyon ve son uygulamadan sonra 5 dakika süreyle test seansları yürütülmüştür. Test sonrasında elde edilen plazmadan adrenokortikotropik hormon, total kortikosteron, serbest kortikosteron, nitrik oksit (total nitrit) ve malondialdehit seviyeleri ölçülmüştür. Diyabetin hayvanlarda kilo kaybına yol açtığı, 100 mg/kg kuersetin uygulamasıyla bu kaybın azaldığı görülmüştür. İki farklı dozdaki kuersetinin diyabete sekonder gelişen hiperglisemi üzerine etkilerinin bulunmadığı belirlenmiştir. Hem diyabetik hem non-diyabetik hayvanlarda 50 mg/kg kuersetin uygulamasının Porsolt testinde total immobil süreyi azaltırken immobilite latensini uzattığı; ancak 100 mg/kg kuersetin uygulamasının diyabetik hayvanlarda total immobil süre ve immobilite latensi üzerine etkisinin bulunmadığı görülmüştür. Kuersetinin kullanılan iki dozunun da diyabetik ve non-diyabetik hayvanlarda adrenokortikotropik hormon, total kortikosteron ve serbest kortikosteron seviyelerini etkilemediği belirlenmiştir. Diyabet veya kuersetin uygulamaları nitrik oksit düzeyini değiştirmediği halde malondialdehit seviyeleri diyabetle birlikte artış göstermiş ve kuersetin uygulamasıyla non-diyabetik hayvanlardaki seviyesine inmiştir. Çalışmamızın sonuçları değerlendirildiğinde 50 mg/kg kuersetin uygulamasının diyabetik deneklerde antidepresan benzeri aktivite sergilediği; ancak söz konusu etkinin 100 mg/kg kuersetin uygulanmasıyla oluşmadığı anlaşılmıştır. Diyabetin hipotalamik-hipofizer-adrenal aksı bozmaması, kullanılan modelin süresiyle ilişkilendirilmişken antidepresan etkinlik gösteren ve göstermeyen kuersetin dozlarının aksı değiştirmemesi nedeniyle kuersetinin diyabetik hayvanlarda görülen antidepresan benzeri etkinliğinin hipotalamik-hipofizer-adrenal akstan bağımsız olduğu sonucuna varılmıştır.
Quercetin, one of the most potent flavonol in the family of flavonoids, has been shown to have health-related beneficial effects. Oxidative stress, inflammation, and hypothalamic-pituitary-adrenal axis disregulation that are regarded to the pathophysiology of depression are also involved in diabetic complications. In our present study, we investigated antidepressant-like properties of quercetin and its effects on hypothalamic-pituitary-adrenal axis in diabetes which conventional antidepressant treatments have limited efficacy due to side effects and poor treatment adherence. To this end, total 45 adult male rats in diabetic and non-diabetic main groups were divided into sub-groups as control, quercetin 50 mg/kg, and quercetin 100 mg/kg. Diabetes was confirmed with blood glucose test 72 hours after a single dose of streptozotocin (60 mg/kg), and quercetin administration and weekly weight measurement were established for 21 days. Blood glucose was measured at day 14 and 21. For the purpose of the forced swim test, acclimatization session was conducted for 15 minutes a day before the last quercetin administration and test session was conducted for 5 minutes just after the last administration. Obtained plasma was used for adrenocorticotropic hormone, total and free corticosterone, nitric oxide (total nitrite), and malondialdehyde evaluations. We found that diabetes resulted to the weight loss, and 100 mg/kg quercetin alleviated this loss. Two separate doses of quercetin had no effect on hyperglycemia that occurred secondarily to diabetes. 50 mg/kg quercetin administration prolonged total immobile time while it shortened immobility latency in the forced swim test in both diabetic and non-diabetic animals, but 100 mg/kg quercetin did not change total immobile time and immobility latency in diabetic animals. Adrenocorticotropic hormone, total and free corticosterone were not affected by both doses of quercetin in diabetic and non-diabetic animals. Diabetes or quercetin administration did not alter nitric oxide levels, but malondialdehyde levels increased with diabetes whilst quercetin administration decreased it to that in non-diabetic animals. We deduced that 50 mg/kg quercetin administration displayed an antidepressant-like activity in diabetics, but this effect had not emerged with 100 mg/kg quercetin administration. We proposed that hypothalamic-pituitary-adrenal axis not being disturbed by diabetes is associated with the used experimental protocol. We concluded that quercetin exhibits antidepressant-like effect in diabetic animals independently to hypothalamic-pituitary-adrenal axis because quercetin doses which showed antidepressant-like effect or not, did not disturb hypothalamic-pituitary-adrenal axis.
Quercetin, one of the most potent flavonol in the family of flavonoids, has been shown to have health-related beneficial effects. Oxidative stress, inflammation, and hypothalamic-pituitary-adrenal axis disregulation that are regarded to the pathophysiology of depression are also involved in diabetic complications. In our present study, we investigated antidepressant-like properties of quercetin and its effects on hypothalamic-pituitary-adrenal axis in diabetes which conventional antidepressant treatments have limited efficacy due to side effects and poor treatment adherence. To this end, total 45 adult male rats in diabetic and non-diabetic main groups were divided into sub-groups as control, quercetin 50 mg/kg, and quercetin 100 mg/kg. Diabetes was confirmed with blood glucose test 72 hours after a single dose of streptozotocin (60 mg/kg), and quercetin administration and weekly weight measurement were established for 21 days. Blood glucose was measured at day 14 and 21. For the purpose of the forced swim test, acclimatization session was conducted for 15 minutes a day before the last quercetin administration and test session was conducted for 5 minutes just after the last administration. Obtained plasma was used for adrenocorticotropic hormone, total and free corticosterone, nitric oxide (total nitrite), and malondialdehyde evaluations. We found that diabetes resulted to the weight loss, and 100 mg/kg quercetin alleviated this loss. Two separate doses of quercetin had no effect on hyperglycemia that occurred secondarily to diabetes. 50 mg/kg quercetin administration prolonged total immobile time while it shortened immobility latency in the forced swim test in both diabetic and non-diabetic animals, but 100 mg/kg quercetin did not change total immobile time and immobility latency in diabetic animals. Adrenocorticotropic hormone, total and free corticosterone were not affected by both doses of quercetin in diabetic and non-diabetic animals. Diabetes or quercetin administration did not alter nitric oxide levels, but malondialdehyde levels increased with diabetes whilst quercetin administration decreased it to that in non-diabetic animals. We deduced that 50 mg/kg quercetin administration displayed an antidepressant-like activity in diabetics, but this effect had not emerged with 100 mg/kg quercetin administration. We proposed that hypothalamic-pituitary-adrenal axis not being disturbed by diabetes is associated with the used experimental protocol. We concluded that quercetin exhibits antidepressant-like effect in diabetic animals independently to hypothalamic-pituitary-adrenal axis because quercetin doses which showed antidepressant-like effect or not, did not disturb hypothalamic-pituitary-adrenal axis.
Açıklama
Anahtar Kelimeler
Antidepresif ajanlar, Antidepressive agents, Depresyon, Depression, Diabetes mellitus, Flavonoidler, Flavonoids, Hipotalamo hipofizeal sistem, Hypothalamo hypophyseal system, Nörofizyoloji, Neurophysiology, Psikofizyoloji, Psychophysiology, Quercetin, Streptozotocin, Sıçanlar, Rats
Kaynak
WoS Q Değeri
Scopus Q Değeri
Cilt
Sayı
Künye
Demir, E. A. (2014). Streptozotosin ile indüklenmiş diyabetik rat modelinde kuersetinin HPA aksı ve depresyona etkisi. Selçuk Üniversitesi, Yayımlanmış doktora tezi, Konya.
