Acrylamide-Induced Neurotoxicity Is Mitigated by Curcumin and Its Nano Lipid Carrier Formulation in Albino Rats

Lobna A Hassanin; Shimaa A Haredy; Enaam A Essa; Christopher J Martyniuk; Amany Sultan

doi:10.1002/tox.70043

Acrylamide-Induced Neurotoxicity Is Mitigated by Curcumin and Its Nano Lipid Carrier Formulation in Albino Rats

Environ Toxicol. 2026 Feb 4. doi: 10.1002/tox.70043. Online ahead of print.

Authors

Lobna A Hassanin¹, Shimaa A Haredy², Enaam A Essa², Christopher J Martyniuk^{3

4}, Amany Sultan^{3

5}

Affiliations

¹ Hormonal Evaluation Department, Egyptian Drug Authority, EDA, Formerly NODCAR, Giza, Egypt.
² Physiology Department, Egyptian Drug Authority, EDA, Formerly NODCAR, Giza, Egypt.
³ Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.
⁴ UF Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, Gainesville, Florida, USA.
⁵ Toxicology Unit, Biochemistry Department, Animal Health Research Institute, Agriculture Research Center, Giza, Egypt.

PMID: 41636267
DOI: 10.1002/tox.70043

Abstract

Acrylamide (AA) exerts neurotoxicity and genotoxicity in wildlife and humans. This study measured the ability of curcumin, an antioxidant, and curcumin Nano lipid carriers (Cur-NLCs) to alleviate biochemical biomarkers of AA-induced neurotoxicity in the cortex and hippocampus of exposed rats. Thirty adult female albino rats were assigned into one of five experimental groups: (1) negative control, (2) vehicle control, (3) acrylamide (50 mg/kg b.wt), (4) acrylamide (50 mg/kg b.wt) with curcumin (100 mg/kg b.wt), and (5) acrylamide (50 mg/kg b.wt) with Cur-NLCs (10 mg/kg b.wt). Treatments were orally administered to rats for 5 days/week for 2 weeks. Acrylamide administration caused body weight loss, abnormal gait, and histopathological damage to both the cortex and hippocampus. Curcumin and Cur-NLCs treatment reduced the occurrence of abnormal behavior and mitigated histopathological changes observed in rats treated with AA. The level of norepinephrine (NE), dopamine (DA), gamma-aminobutyric acid (GABA), serotonin (5-HT), reduced glutathione (GSH), and adenosine triphosphate (ATP) were all decreased with AA treatment. Following treatment with curcumin, AA-induced reductions in glutathione (GSH), dopamine (DA), 5-hydroxy indole acetic acid (5-HIAA), norepinephrine (NE), adenosine monophosphate (AMP), aspartate (ASP), and gamma-aminobutyric acid were restored to the control level in the cortex. In the hippocampus, GSH, 8-hydroxydeoxyguanosine (8-OHdG), DA, 5-hydroxy tryptamine (5-HT), 5-HIAA, NE, ATP, ASP, GABA and glutamate (Glu) improved to that observed in control rats. Co-treatment with Cur-NLCs also had protective effects on malondialdehyde (MDA) and NE in the cortex, and 5-HIAA and ASP in the hippocampus. Upon comparison, Cur-NLCs at 10 mg/kg/day showed less benefit than curcumin alone (100 mg/kg/day) based on several endpoints of oxidative stress, DNA damage, and histopathology. We conclude there are tissue specific responses to these formulations in the CNS and suggest that a more effective means of treating AA-induced neurotoxicity with these antioxidants may be a mixture of both unmodified curcumin and its Nano-formulation.

Keywords: DNA damage; acrylamide; brain; curcumin; nanoparticles; neurotransmitters; oxidative stress.