Silymarin protects against acrylamide-induced neurotoxicity via Nrf2 signalling in PC12 cells.

Abstract

Silymarin (SM) is a well-known antioxidant, anti-inflammatory and anti-cancer compound extracted from the milk thistle. Here, we investigated the protective effect of SM against acrylamide (AA)-induced neurotoxicity, mainly caused by oxidative stress, via activation of the nuclear transcription factor E2-related factor 2 (Nrf2) signalling pathway in PC12 cells. The MTT reduction assay was used to measure cell viability in various drug-treated groups and demonstrated that SM could increase cell viability in AA-treated PC12 cells. We then measured the reactive oxygen species (ROS) levels by the peroxide-sensitive fluorescent probe DCFH-DA and intracellular glutathione (GSH) and malondialdehyde (MDA) levels by absorption spectrophotometry. Our data revealed that SM could reduce ROS and MDA levels and increase GSH levels in AA-induced PC12 cells. To identify a potential mechanism for SM-induced protection, we measured the mRNA and protein expression levels of Nrf2 and its downstream target antioxidants glutathione peroxidase (Gpx), glutamate cysteine ligase catalytic subunit (GCLC) and glutamate cysteine ligase modifier subunit (GCLM) by quantitative real-time PCR and Western blot, respectively. The results suggested that SM could activate Nrf2 signalling and increase the expression of Nrf2, Gpx, GCLC and GCLM in AA-treated PC12 cells. In conclusion, SM can effectively alleviate AA-induced neurotoxicity in PC12 cells.

• Authors: Liang Li, Hong-Yang Sun, Wei Liu, Hong-Yu Zhao, Mei-Li Shao
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 102 Pg. 93-101 (Apr 2017) ISSN: 1873-6351 [Electronic] England
• PMID: 28137608 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Reactive Oxygen Species
• Silymarin
• Acrylamide
• Malondialdehyde
• Glutathione Peroxidase
• GCLM protein, rat
• Glutamate-Cysteine Ligase
• GCLC protein, rat
• Glutathione

Topics

• Acrylamide (toxicity)
• Animals
• Gene Expression Regulation (drug effects)
• Glutamate-Cysteine Ligase (genetics, metabolism)
• Glutathione (metabolism)
• Glutathione Peroxidase (genetics, metabolism)
• Malondialdehyde (metabolism)
• NF-E2-Related Factor 2 (genetics, metabolism)
• Neurotoxicity Syndromes (metabolism, prevention & control)
• PC12 Cells (drug effects, metabolism, pathology)
• Rats
• Reactive Oxygen Species (metabolism)
• Silymarin (pharmacology)