Is oxidative stress the mechanism of blue sac disease in retene-exposed trout larvae?
Retene (7-isopropyl-1-methylphenanthrene) causes blue sac disease (BSD) in early life stages of fish, an effect similar to that of 2,3,7,8-tetrachlorodibenzo(p)dioxin. The signs of BSD include cytochrome P450 (CYP1A) induction, edema, hemorrhaging, and craniofacial deformities, indicating membrane damage, circulatory failure, and impaired development. To test if the underlying cause was oxidative stress, rainbow trout (Oncorhynchus mykiss) larvae were exposed to waterborne retene or to known prooxidants (paraquat, t-butyl hydroperoxide, and carbon tetrachloride) in the presence or absence of vitamin E, an antioxidant. Fish exposed to retene showed an increased prevalence of BSD, reduced tissue concentrations of vitamin E and total glutathione, and a lower percentage of glutathione in a reduced form. Coexposure to vitamin E reduced the prevalence of BSD and restored tissue concentrations of vitamin E, but it did not affect retene uptake or tissue concentrations of glutathione. These responses are consistent with oxidative stress as a mode of action of retene. However, retene did not affect whole-body lipid peroxide concentrations, and prooxidants did not affect the prevalence of BSD and had only minimal effects on tissue glutathione and vitamin E. Possible explanations for these conflicting results include prooxidant exposures were insufficient to generate oxidative stress; lipid peroxidation may not be measurable in whole-body homogenates of retene-exposed fish if effects are localized to endothelial cells, where CYP1A enzymes are most induced; or retene may have an alternate mode of action (e.g., adduction of retene metabolites to lipids, protein, or DNA).
Bauder
Matthew B
MB
Environment Canada, 351 St-Joseph Boulevard, Hull, Quebec K1A 0H3, Canada
Palace
Vincent P
VP
Hodson
Peter V
PV
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004790:Enzyme Induction; D005393:Fish Diseases / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000196:embryology* / Q000378:metabolism; D018384:Oxidative Stress; D010616:Phenanthrenes / Q000633:toxicity*; D014810:Vitamin E / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D008054:Lipid Peroxides; D010616:Phenanthrenes; D014874:Water Pollutants, Chemical; C447880:retene; D014810:Vitamin E; D019363:Cytochrome P-450 CYP1A1; D005978:Glutathione