Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats

Neurovascular dysfunction leads to the second most common type of dementia, i.e., vascular dementia (VaD). Toxic metals, such as aluminium, increase the risk of neurovascular dysfunction-associated VaD. Hence, we hypothesized that a natural antioxidant derived from palm oil, i.e., tocotrienol-rich f...

Full description

Bibliographic Details
Main Authors: Sohrab A. Shaikh, Arunachalam Muthuraman
Format: Article
Language:English
Published: MDPI AG 2023-06-01
Series:Pharmaceuticals
Subjects:
Online Access:https://www.mdpi.com/1424-8247/16/6/828
_version_ 1797593115334279168
author Sohrab A. Shaikh
Arunachalam Muthuraman
author_facet Sohrab A. Shaikh
Arunachalam Muthuraman
author_sort Sohrab A. Shaikh
collection DOAJ
description Neurovascular dysfunction leads to the second most common type of dementia, i.e., vascular dementia (VaD). Toxic metals, such as aluminium, increase the risk of neurovascular dysfunction-associated VaD. Hence, we hypothesized that a natural antioxidant derived from palm oil, i.e., tocotrienol-rich fraction (TRF), can attenuate the aluminium chloride (AlCl<sub>3</sub>)-induced VaD in rats. Rats were induced with AlCl<sub>3</sub> (150 mg/kg) intraperitoneally for seven days followed by TRF treatment for twenty-one days. The elevated plus maze test was performed for memory assessment. Serum nitrite and plasma myeloperoxidase (MPO) levels were measured as biomarkers for endothelial dysfunction and small vessel disease determination. Thiobarbituric acid reactive substance (TBARS) was determined as brain oxidative stress marker. Platelet-derived growth factor-C (PDGF-C) expression in the hippocampus was identified using immunohistochemistry for detecting the neovascularisation process. AlCl<sub>3</sub> showed a significant decrease in memory and serum nitrite levels, while MPO and TBARS levels were increased; moreover, PDGF-C was not expressed in the hippocampus. However, TRF treatment significantly improved memory, increased serum nitrite, decreased MPO and TBARS, and expressed PDGF-C in hippocampus. Thus, the results imply that TRF reduces brain oxidative stress, improves endothelial function, facilitates hippocampus PDGF-C expression for neovascularisation process, protects neurons, and improves memory in neurovascular dysfunction-associated VaD rats.
first_indexed 2024-03-11T02:03:15Z
format Article
id doaj.art-7565f1511baa43539624bfe215e957b0
institution Directory Open Access Journal
issn 1424-8247
language English
last_indexed 2024-03-11T02:03:15Z
publishDate 2023-06-01
publisher MDPI AG
record_format Article
series Pharmaceuticals
spelling doaj.art-7565f1511baa43539624bfe215e957b02023-11-18T12:02:05ZengMDPI AGPharmaceuticals1424-82472023-06-0116682810.3390/ph16060828Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in RatsSohrab A. Shaikh0Arunachalam Muthuraman1Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, Bedong 08100, Kedah, MalaysiaPharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, Bedong 08100, Kedah, MalaysiaNeurovascular dysfunction leads to the second most common type of dementia, i.e., vascular dementia (VaD). Toxic metals, such as aluminium, increase the risk of neurovascular dysfunction-associated VaD. Hence, we hypothesized that a natural antioxidant derived from palm oil, i.e., tocotrienol-rich fraction (TRF), can attenuate the aluminium chloride (AlCl<sub>3</sub>)-induced VaD in rats. Rats were induced with AlCl<sub>3</sub> (150 mg/kg) intraperitoneally for seven days followed by TRF treatment for twenty-one days. The elevated plus maze test was performed for memory assessment. Serum nitrite and plasma myeloperoxidase (MPO) levels were measured as biomarkers for endothelial dysfunction and small vessel disease determination. Thiobarbituric acid reactive substance (TBARS) was determined as brain oxidative stress marker. Platelet-derived growth factor-C (PDGF-C) expression in the hippocampus was identified using immunohistochemistry for detecting the neovascularisation process. AlCl<sub>3</sub> showed a significant decrease in memory and serum nitrite levels, while MPO and TBARS levels were increased; moreover, PDGF-C was not expressed in the hippocampus. However, TRF treatment significantly improved memory, increased serum nitrite, decreased MPO and TBARS, and expressed PDGF-C in hippocampus. Thus, the results imply that TRF reduces brain oxidative stress, improves endothelial function, facilitates hippocampus PDGF-C expression for neovascularisation process, protects neurons, and improves memory in neurovascular dysfunction-associated VaD rats.https://www.mdpi.com/1424-8247/16/6/828endothelial dysfunctionmyeloperoxidaseplatelet-derived growth factor-Cserum nitritetocotrienol-rich fractionvascular dementia
spellingShingle Sohrab A. Shaikh
Arunachalam Muthuraman
Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats
Pharmaceuticals
endothelial dysfunction
myeloperoxidase
platelet-derived growth factor-C
serum nitrite
tocotrienol-rich fraction
vascular dementia
title Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats
title_full Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats
title_fullStr Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats
title_full_unstemmed Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats
title_short Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats
title_sort tocotrienol rich fraction ameliorates the aluminium chloride induced neurovascular dysfunction associated vascular dementia in rats
topic endothelial dysfunction
myeloperoxidase
platelet-derived growth factor-C
serum nitrite
tocotrienol-rich fraction
vascular dementia
url https://www.mdpi.com/1424-8247/16/6/828
work_keys_str_mv AT sohrabashaikh tocotrienolrichfractionamelioratesthealuminiumchlorideinducedneurovasculardysfunctionassociatedvasculardementiainrats
AT arunachalammuthuraman tocotrienolrichfractionamelioratesthealuminiumchlorideinducedneurovasculardysfunctionassociatedvasculardementiainrats