High glucuronidation activity of environmental estrogens in the carp (Cyprinus carpino) intestine

Abstract

Many adverse effects on carp reproductive organs have been reported to be caused by exposure to environmental estrogens, such as nonylphenol and bisphenol A, which contaminate the aquatic environment. The glucuronidation activities of xenoestrogens (bisphenol A and diethylstilbestrol) and phytoestrogens (coumestrol, genistein and biochanin A), but not nonylphenol and octylphenol, were observed in microsomes prepared from carp organs. The highest levels of glucuronidation of environmental estrogens, for which the optimum temperature was 25–30 °C, were observed in the intestinal microsomes of 2-year-old carp. These activities in carp intestine increased developmentally, and the maximum levels corresponded to 5–10 % of that in rat liver microsomes. However, the glucuronidation of phytoestrogen by carp intestinal microsomes corresponded to that of rat liver microsomes. Only bisphenol A-glucuronide was excreted from the everted intestine, indicating that bisphenol A is metabolized in the carp intestine mainly as glucuronide.

These results suggest that glucuronidation by carp intestine plays an important role for the detoxification of xenoestrogens and phytoestrogens, except for nonylphenol and octylphenol.

Introduction

Much evidence has recently been reported on the hormone-like effects of environmental chemicals in fish, wildlife and humans [1]. Bisphenol A, which is a monomer used in the manufacture of polycarbonate, and alkylphenols (nonylphenol and octylphenol), which are compounds widely used as plastic additives and for the manufacture of surfactants, have been reported to have estrogenic activities [2], [3], [4]. Significant amounts of these alkylphenols have been found in the aquatic environment, especially in sediments [5], [6]. Alkylphenolic compounds can bioaccumulate in fish and potentially impair reproduction or development through estrogenic actions [7], [8], [9], [10]. Feminized male fishes have been found near sewage outlets in several rivers in the U.K.; a mixture of chemicals including alkylphenols resulting from degradation of detergents during sewage treatment seemed to be the causal agent of this endocrine disruption [11]. Fishes such as carp may be sensitive to these polluted chemicals. The precise mechanisms of action of a number of these xenoestrogens are still not known.

Bisphenol A and nonylphenol are mainly glucuronidated in the liver and excreted into the bile of rats [12], [13], [14] and rainbow trout (Oncorhynchus mykiss) [15], [16]. Recently, plasma xenoestrogen biomarkers such as viterogennin and zona radiata proteins were shown to be induced by intraperitoneal injections of bisphenol A and nonylphenol into juvenile salmon [17]. The metabolism of these chemicals in fish must be determined in order to elucidate the mechanisms of viterogennin induction and endocrine disruptions. It is basically important to know whether xenobiotic pollutants, such as bisphenol A and nonylphenol, are glucuronidated in the organs of fishes that have sustained adverse effects for estimation of toxicity of these chemicals.