Ex vivo investigation of betaine and boric acid function as preprotective agents on rat synaptosomes to be treated with A? (1-42)

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Tarih

2024

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Dergi ISSN

Cilt Başlığı

Yayıncı

Wiley

Erişim Hakkı

info:eu-repo/semantics/openAccess

Özet

Recent evidence suggests that ferroptosis, an iron-dependent cell death process, may be involved in Alzheimer's disease (AD) pathology. The study evaluated the therapeutic potential of betaine and boric acid (BA) pretreatment administered to rats for 21 days in AD. Then, the rats were sacrificed, and morphological and biochemical analyses were performed in brain tissues. Next, an ex vivo AD model was created by applying amyloid-beta (A beta 1-42) to synaptosomes isolated from the brain tissues. Synaptosomes were analyzed with micrograph images, and protein and mRNA levels of ferroptotic markers were determined. Betaine and BA pretreatments did not cause any morphological and biochemical differences in the brain tissue. However, A beta (1-42) administration in synaptosomes increased the levels of acyl-CoA synthetase long chain family member-4 (ACSL4), transferrin receptor-1 protein (TfR1), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) and decreased the levels glutathione peroxidase-4 (GPx4) and glutathione (GSH). Moreover, ACSL4, GPx4, and TfR1 mRNA and protein levels were similar to the ELISA results. In contrast, betaine and BA pretreatments decreased the levels of ACSL4, TfR1, MDA, and 8-OHdG in synaptosomes incubated with A beta 1-42, while promoting increased levels of GPx4 and GSH. In addition, betaine and BA pretreatments completely reversed ACSL4, GPx4, and TfR1 mRNA and protein levels. Therefore, betaine and BA pretreatments may contribute to the prevention of neurodegenerative damage by supporting antiferroptotic activities.

Açıklama

Anahtar Kelimeler

Alzheimer's disease, betaine, boric acid, ferroptosis, iron metabolism, TfR, Glutathione-Peroxidase 4, Alzheimers-Disease, Iron, Transferrin, Brain

Kaynak

Environmental Toxicology

WoS Q Değeri

Q1

Scopus Q Değeri

Q2

Cilt

39

Sayı

4

Künye