Tauroursodeoksikolik asit tedavisinin karaciğer fonksiyonları, plazma lipit profili ve oksidatif stres üzerindeki etkilerinin yaşlanmaya ve cinsiyete bağlı değişimi

Amaç: Yaşlanma vücutta çoklu ve sistemik işlev bozuklukları ile ilişkilidir, bu durumlara metabolizma bozuklukları ve oksidatif stres eşlik etmektedir. Endoplazmik retikulum (ER) stresinin yaşlanmaya bağlı patolojilerdeki rolünü gösteren çalışmalar olmakla birlikte bu ilişki tam olarak aydınlatılamamıştır. Bu çalışmada, karaciğer fonksiyonu, plazma lipitleri ve oksidatif stres belirteçlerinin yaşlanmaya ve cinsiyete bağlı değişimlerinin ortaya konması ayrıca bu parametrelerin ER stres inhibitörü tauro-ursodeoksikolik asit (TUDCA) tedavisiyle nasıl değiştiğinin araştırılması amaçlanmıştır. Gereç ve Yöntem: Deneylerde genç (4 aylık) ve yaşlı (24 aylık) Wistar albino erkek ve dişi sıçanlar kullanılmıştır. ER stres inhibitörü olarak TUDCA uygulaması 4 hafta süresince yapılmıştır (150 mg/kg/gün, ip). Plazma örneklerinde karaciğer fonksiyon belirteçleri (AST ve ALT), plazma lipitleri (LDL, HDL, TG ve total kolesterol) ve oksidatif stres biyobelirteçlerinin (malondialdehit, (MDA) ve miyeloperoksidaz (MPO)) seviyeleri ölçülmüştür.. Bulgular: Bu çalışmada TUDCA ile ER stres inhibisyonunun yaşlılarda AST seviyelerini azattığı, HDL değerini yükseltirken TG değerini düşürdüğü, MDA ve MPO düzeylerini azalttığı gösterilmiştir. Bazı parametreler üzerindeki etkileri cinsiyete bağlı olarak değişim göstermiştir. Sonuç: Oksidatif stres ve metabolik bozuklukların yaşa bağlı pek çok hastalığın patogenezindeki rolü göz önüne alındığında; bu sonuçların yaşlanmada ER stres inhibisyonunu hedef alan tedavi yaklaşımlarının geliştirilmesine katkı sunacağı düşünülmektedir.

Anahtar Kelimeler:

yaşlanma, endoplazmik retikulum stresi, oksidatif stres, dislipidemi

Aging and gender-related effects of tauroursodeoxycholic acid treatment on liver functions, plasma lipid profile, and oxidative stress

Purpose: Aging is related to multiple and systemic dysfunctions in the body, accompanied by metabolic disorders and oxidative stress. Although studies are revealing the role of endoplasmic reticulum (ER) stress in aging-related pathologies, this relationship has not been fully elucidated. In this study, it was aimed to reveal changes in liver function, plasma lipids, and oxidative stress markers due to aging and gender, and to investigate how these parameters change with ER stress inhibitor tauro-ursodeoxycholic acid (TUDCA) treatment. Materials and Methods: Young (4 months old) and old (24 months old) Wistar albino male and female rats were used in the experiments. The administration of ER stress inhibitor TUDCA was performed for 4 weeks (150 mg/kg/day, ip). Liver function markers (AST and ALT), plasma lipids (LDL, HDL, TG and total cholesterol), and oxidative stress biomarkers (malondialdehyde, (MDA) and myeloperoxidase (MPO)) levels were measured in plasma samples. Results: ER stress inhibition with TUDCA decreased AST levels, increased HDL value, decreased TG value, and decreased MDA and MPO levels in the elderly. The effects on some parameters varied depending on gender. Conclusion: Considering the role of oxidative stress and metabolic disorders in the pathogenesis of many age-related diseases, it is thought that these results will contribute to the development of treatment approaches targeting ER stress inhibition in aging.

Keywords:

Aging, endoplasmic reticulum stress, oxidative stress, dyslipidemia.,

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