دورية أكاديمية

Positive Feedback Mechanism in Aristolochic Acid I Exposure-Induced Anemia and DNA Adduct Formation: Implications for Balkan Endemic Nephropathy.

التفاصيل البيبلوغرافية
العنوان: Positive Feedback Mechanism in Aristolochic Acid I Exposure-Induced Anemia and DNA Adduct Formation: Implications for Balkan Endemic Nephropathy.
المؤلفون: Ham YH; Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong., Chin ML; Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong., Pan G; Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong., Wang S; Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong., Pavlović NM; Medical Faculty, University of Niš, 18000 Niš, Serbia., Chan W; Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong.
المصدر: Journal of agricultural and food chemistry [J Agric Food Chem] 2024 Aug 01. Date of Electronic Publication: 2024 Aug 01.
Publication Model: Ahead of Print
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0374755 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5118 (Electronic) Linking ISSN: 00218561 NLM ISO Abbreviation: J Agric Food Chem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, American Chemical Society.
مستخلص: Balkan endemic nephropathy (BEN) is a chronic kidney disease that predominantly affects inhabitants of rural farming communities along the Danube River tributaries in the Balkans. Long-standing research has identified dietary exposure to aristolochic acids (AAs) as the principal toxicological cause. This study investigates the pathophysiological role of anemia in BEN, noting its earlier and more severe manifestation in BEN patients compared to those with other chronic kidney diseases. Utilizing a mouse model, our research demonstrates that prolonged exposure to aristolochic acid I (AA-I) (the most prevalent AA variant) leads to significant red blood cell depletion through DNA damage, such as DNA adduct formation in bone marrow, prior to observable kidney function decline. Furthermore, in vitro experiments with kidney cells exposed to lowered oxygen and pH conditions mimicking an anemia environment show enhanced DNA adduct formation, suggesting increased AA-I mutagenicity and carcinogenicity. These findings indicate for the first time a positive feedback mechanism of AA-induced anemia, DNA damage, and kidney impairment in BEN progression. These results not only advance our understanding of the underlying mechanisms of BEN but also highlight anemia as a potential target for early BEN diagnosis and therapy.
فهرسة مساهمة: Keywords: Balkan endemic nephropathy; DNA adduct; anemia; aristolochic acids; dietary exposure
تواريخ الأحداث: Date Created: 20240801 Latest Revision: 20240801
رمز التحديث: 20240802
DOI: 10.1021/acs.jafc.4c03508
PMID: 39088813
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-5118
DOI:10.1021/acs.jafc.4c03508