Effluent from drug manufacturing affects cytochrome P450 1 regulation and function in fish

• We have previously reported very high concentrations of pharmaceuticals in the effluent from a treatment plant receiving wastewater from about 90 bulk drug manufacturers near Hyderabad, India. The main objective of the present study was to examine how high dilutions of this effluent affect mRNA expression of cytochrome P450 (CYP) 1 family genes and ethoxyresorufin O-deethylase (EROD) activity in exposed wildlife, using the three-spined stickleback (Gasterosteus aculeatus) as a model. In gill filaments exposed to diluted effluent ex vivo, EROD activity was strongly inhibited in a concentration-dependent manner. In a subsequent in vivo study, groups of fish were exposed (24. h) to three concentrations of effluent, 0.8%, 1.6% or 3.2%. In this experiment, EROD in gills was induced 27-, 52- or 60-fold, respectively. Accordingly, CYP1A mRNA was markedly up-regulated in gill, liver and brain of fish exposed to all three effluent concentrations. Expression of mRNA for CYP1B1 and CYP1C1 was induced in gills at all concentrations while effects on these genes in liver and brain were weak or absent. The results of a time course study suggested that most CYP1-inducing substances in the effluent were readily metabolised or excreted, because the induced EROD activity and mRNA expression decreased when the fish were transferred to clean water. Considering that CYP1 enzymes play important roles in biotransformation of endogenous and foreign compounds, the observed dual effect of the effluent on CYP1 catalytic activity and mRNA expression suggests that multiple physiological functions could be affected in exposed wildlife.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

CYP1

EROD

Gills

Pharmaceuticals

Three-spined stickleback

Treated wastewater

Drug products

Effluent treatment

Fish

Gene expression

Wastewater treatment

Effluents

cytochrome P450

cytochrome P450 1

cytochrome P450 1A

cytochrome P450 1B1

cytochrome P450 1C1

cytochrome P450 1C2

ethoxyresorufin deethylase

industrial effluent

messenger RNA

tap water

unclassified drug

biotransformation

concentration (composition)

drug

ecological modeling

effluent

enzyme activity

manufacturing

metabolism

pollution exposure

teleost

wastewater

water treatment

animal experiment

animal tissue

article

brain

controlled study

enzyme induction

enzyme inhibition

female

Gasterosteus aculeatus

gene

genetic transcription

gill

liver

mortality

nonhuman

spiggin gene

upregulation

vitellogenin gene

waste water treatment plant

Andhra Pradesh

Hyderabad [Andhra Pradesh]

India

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