| Autor: |
Saxena B; Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, India., Parmar P; Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, India., Chauhan H; Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, India., Singh P; Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli, Lucknow, India., Datusalia AK; Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli, Lucknow, India., Vyas VK; Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad, India., Tripathi N; Department of Pharmacognosy, Institute of Pharmacy, Nirma University, Ahmedabad, India., Shah J; Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, India. |
| Jazyk: |
angličtina |
| Zdroj: |
Toxicology mechanisms and methods [Toxicol Mech Methods] 2024 Jul; Vol. 34 (6), pp. 703-716. Date of Electronic Publication: 2024 Mar 25. |
| DOI: |
10.1080/15376516.2024.2329653 |
| Abstrakt: |
Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl 3 ) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl 3 -induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 μM) was tested against AlCl 3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 ( h MD-2) was investigated. AlCl 3 (25 mg/kg/d, i.p. ) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p. ) was given along with AlCl 3 . This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with h MD-2 was found to be -4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl 3 in both C6 and SH-SY5Y cells. Treatment with 10 μM taxifolin restored AlCl 3 -induced altered cell morphology. AlCl 3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl 3 -induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl 3 administration in rats. Thus, taxifolin may protect the brain against AD. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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