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Alterations in hepatic mixed-function oxidase activity of rainbow trout after acute treatment with polybrominated
Abstract:
The effects of FireMaster BP-6 and several pure isomers on hepatic microsomal mixed-function oxidase (MFO) activity in rainbow trout have been investigated. After one parenteral injection of these agents at 150 mg/kg and sacrifice 5 d later, there was no elevation of hepatic cytochrome P-450. The noncoplanar isomers 2,4,5,2',4',5'-hexa and 2,3,4,5,2',4',5'-heptabromobiphenyl did not increase any MFO activity generally associated with an increase in cytochrome P-450 levels, including the dealkylations of ethoxycoumarin and benzphetamine. The coplanar isomer 3,4,5,3',4',5'-hexabromobiphenyl produced an increase in O-deethylation of both ethoxycoumarin and ethoxyresorufin, suggesting enhancement of cytochrome P-448 associated activity, but produced no increase in benzphetamine N-dealkylation. The "mixed inducer" 2,4,5,3',4',5'-hexabromobiphenyl, produced a small but insignificant elevation of cytochrome P-448 associated MFO activities and no increase in cytochrome P-450 associated activities. At both 150 and 500 mg/kg, the commercial mixture of polybrominated biphenyls FireMaster BP-6 produced marked elevations of both ethoxycoumarin and ethoxy-resorufin dealkylations but had no effect on demethylation of benzphetamine. When microsomes from rainbow trout treated with FireMaster BP-6 were examined electrophoretically, A coomassie Blue-staining band at 57,000 daltons was intensified, as seen after treatment of fish with the cytochrome P-448 inducer beta-naphthoflavone. It is concluded that coplanar polybrominated isomers produce an induction of hepatic cytochrome P-448 associated activity, while noncoplanar isomers are ineffective as inducers of cytochrome P-450 related MFO activities in rainbow trout.
Insights
Polybrominated biphenyls impact rainbow trout liver enzymes. Coplanar isomers induce cytochrome P-448 activity, while noncoplanar isomers do not affect cytochrome P-450 related mixed-function oxidase activities.
Area of Science:
- Environmental Toxicology
- Biochemistry
- Fish Biology
Background:
- Polybrominated biphenyls (PBBs) are persistent organic pollutants.
- Hepatic microsomal mixed-function oxidase (MFO) systems are crucial for xenobiotic metabolism in fish.
- Understanding PBB isomer-specific effects on MFO activity is vital for assessing ecological risk.
Purpose of the Study:
- To investigate the differential effects of FireMaster BP-6 and its isomers on rainbow trout hepatic MFO activity.
- To determine whether coplanar or noncoplanar PBBs are more potent inducers of specific cytochrome P450 isoforms.
Main Methods:
- Parenteral injection of PBBs (FireMaster BP-6 and pure isomers) into rainbow trout.
- Measurement of hepatic microsomal MFO activities, including ethoxycoumarin O-deethylation, ethoxyresorufin O-deethylation, and benzphetamine N-dealkylation.
- Electrophoretic analysis of microsomal proteins to identify changes in specific bands.
Main Results:
- Noncoplanar PBB isomers did not elevate cytochrome P-450 associated MFO activities.
- Coplanar PBB isomers induced cytochrome P-448 associated O-deethylation activities.
- FireMaster BP-6 significantly increased O-deethylation but not N-dealkylation, consistent with P448 induction.
Conclusions:
- Coplanar polybrominated biphenyl isomers are inducers of hepatic cytochrome P-448 associated activity in rainbow trout.
- Noncoplanar isomers are ineffective inducers of cytochrome P-450 related MFO activities.
- These findings highlight the importance of isomeric composition in PBB toxicity and bioactivation.