How can nanomicelle-curcumin modulate aluminum phosphide-induced neurotoxicity?: Role of SIRT1/FOXO3 signaling pathway

Milad Khodavysi; Nejat Kheiripour; Hassan Ghasemi; Sara Soleimani-Asl; Ali Fathi Jouzdani; Mohammadmahdi Sabahi; Zahra Ganji; Zahra Azizi; Akram Ranjbar; Milad Khodavysi; Nejat Kheiripour; Hassan Ghasemi; Sara Soleimani-Asl; Ali Fathi Jouzdani; Mohammadmahdi Sabahi; Zahra Ganji; Zahra Azizi; Akram Ranjbar

doi:10.3934/Neuroscience.2023005

AIMS Neuroscience

2023, Volume 10, Issue 1: 56-74. doi: 10.3934/Neuroscience.2023005

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Research article

How can nanomicelle-curcumin modulate aluminum phosphide-induced neurotoxicity?: Role of SIRT1/FOXO3 signaling pathway

1.
Department of Pharmacology and Toxicology, School of Pharmacy, Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
2.
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
3.
Department of Clinical Biochemistry, Abadan University of Medical Sciences, Abadan, Iran
4.
Department of Anatomical Sciences, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
5.
Neuroscience and Artificial Intelligence Research Group (NAIRG), Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
6.
USERN office, Hamadan University of Medical Sciences, Hamadan, Iran
7.
Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

Received: 14 November 2022 Revised: 22 March 2023 Accepted: 27 March 2023 Published: 04 April 2023

Aluminum phosphide (ALP) is among the most significant causes of brain toxicity and death in many countries. Curcumin (CUR), a major turmeric component, is a potent protective agent against many diseases, including brain toxicity. This study aimed to examine the probable protection potential of nanomicelle curcumin (nanomicelle-CUR) and its underlying mechanism in a rat model of ALP-induced brain toxicity. A total of 36 Wistar rats were randomly divided into six groups (n = 6) and exposed to ALP (2 mg/kg/day, orally) + CUR or nanomicelle-CUR (100 mg/kg/day, orally) for 7 days. Then, they were anesthetized, and brain tissue samples were dissected to evaluate histopathological alterations, oxidative stress biomarkers, gene expression of SIRT1, FOXO1a, FOXO3a, CAT and GPX in brain tissue via hematoxylin and eosin (H&E) staining, biochemical and enzyme-linked immunosorbent assay (ELISA) methods and Real-Time PCR analysis. CUR and nanomicelle-CUR caused significant improvement in ALP-induced brain damage by reducing the MDA levels and induction of antioxidant capacity (TTG, TAC and SOD levels) and antioxidant enzymes (CAT, GPX), modulation of histopathological changes and up-regulation of gene expression of SIRT1 in brain tissue. It was concluded that nanomicelle-CUR treatment ameliorated the harmful effects of ALP-induced brain toxicity by reducing oxidative stress. Therefore, it could be considered a suitable therapeutic choice for ALP poisoning.
- aluminum phosphide,
- brain,
- curcumin,
- nanomicelle-curcumin,
- oxidative stress
Citation: Milad Khodavysi, Nejat Kheiripour, Hassan Ghasemi, Sara Soleimani-Asl, Ali Fathi Jouzdani, Mohammadmahdi Sabahi, Zahra Ganji, Zahra Azizi, Akram Ranjbar. How can nanomicelle-curcumin modulate aluminum phosphide-induced neurotoxicity?: Role of SIRT1/FOXO3 signaling pathway[J]. AIMS Neuroscience, 2023, 10(1): 56-74. doi: 10.3934/Neuroscience.2023005

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Abstract

Aluminum phosphide (ALP) is among the most significant causes of brain toxicity and death in many countries. Curcumin (CUR), a major turmeric component, is a potent protective agent against many diseases, including brain toxicity. This study aimed to examine the probable protection potential of nanomicelle curcumin (nanomicelle-CUR) and its underlying mechanism in a rat model of ALP-induced brain toxicity. A total of 36 Wistar rats were randomly divided into six groups (n = 6) and exposed to ALP (2 mg/kg/day, orally) + CUR or nanomicelle-CUR (100 mg/kg/day, orally) for 7 days. Then, they were anesthetized, and brain tissue samples were dissected to evaluate histopathological alterations, oxidative stress biomarkers, gene expression of SIRT1, FOXO1a, FOXO3a, CAT and GPX in brain tissue via hematoxylin and eosin (H&E) staining, biochemical and enzyme-linked immunosorbent assay (ELISA) methods and Real-Time PCR analysis. CUR and nanomicelle-CUR caused significant improvement in ALP-induced brain damage by reducing the MDA levels and induction of antioxidant capacity (TTG, TAC and SOD levels) and antioxidant enzymes (CAT, GPX), modulation of histopathological changes and up-regulation of gene expression of SIRT1 in brain tissue. It was concluded that nanomicelle-CUR treatment ameliorated the harmful effects of ALP-induced brain toxicity by reducing oxidative stress. Therefore, it could be considered a suitable therapeutic choice for ALP poisoning.

Acknowledgments

At this moment, we extend our gratitude to the Vice-Chancellor of Research at Hamadan University of Medical Sciences for the financial support of this study (Grant number: 9612228342).

Future Perspective

In this study, curcumin and nanomicelle-curcumin had neuroprotective properties and the ability to modulate oxidative stress conditions in the brain. In many neurodegenerative disorders, including Alzheimer's, Parkinson's and strokes, oxidative stress plays a vital role in their pathogenesis. According to this study's findings, curcumin, especially nanocurcumin, may be effective in treating these neurodegenerative diseases by modulating the effects of oxidative stress in the brain.

Conflict of interest

The authors reported no potential conflict of interest.

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