Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish
- Authors
- Wang, L., and Gallagher, E.P.
- ID
- ZDB-PUB-121205-45
- Date
- 2013
- Source
- Toxicology and applied pharmacology 266(2): 177-186 (Journal)
- Registered Authors
- Gallagher, Evan P., Wang, Lu
- Keywords
- Nrf2, cadmium, oxidative stress, zebrafish, olfactory injury
- MeSH Terms
-
- Animals
- Antioxidants/metabolism*
- Cadmium/toxicity*
- Dose-Response Relationship, Drug
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental/drug effects
- Gene Knockdown Techniques
- Isothiocyanates
- NF-E2-Related Factor 2/metabolism*
- Olfactory Pathways/drug effects*
- Oxidative Stress/drug effects*
- Thiocyanates/pharmacology
- Time Factors
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 23174481 Full text @ Tox. App. Pharmacol.
- CTD
- 23174481
Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidative stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function.