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

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.