Response of xenobiotic metabolizing enzymes in rainbouw trout (Oncorhynchus mykiss) to endosulfan, detected by enzyme activities and immunochemical methods

Jensen, Elisabeth Gram; Skaare, Janneche Utne; Egaas, Eliann; Goksøyr, Anders

doi:10.1016/0166-445x(91)90007-v

Cited by 33 publications

(10 citation statements)

References 28 publications

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“…In the rat, endosulfan was actually shown to stimulate a n increase in hepatic microsomal protein and to function as a weak inducer of biotransformation enzymes (Den Tonkelaar & Van Esch 1974, Tyagi et al 1984, Siddiqui et al 1987 and to provoke an increase of SER membranes (Agarwal et al 1978, Tyagi et al 1984. Similarly, endosulfan has been shown to induce hepatic phase I biotransformation enzymes including cytochrome P450 (Jensen et al 1991). The fact that most of the endosulfan metabolites are excreted via the bile indicates that the liver is the major site of endosulfan metabolism and excretion in fish (Schoettger 1970, Rao & Murty 1982, Herzberg 1986).…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural alterations in the liver and intestine of carp Cyprinus carpio induced orally by ultra-low doses of endosulfan

Braunbeck¹,

Appelbaum²

1999

Dis. Aquat. Org.

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In order to elucidate the importance of food-borne chemical contamination in fish, cytological and ultrastructural alterations in hepatocytes and enterocytes of common carp Cyprinus carpio L. exposed for 5 wk to 0.5 pg endosulfan (6,7,8.9,10,10-hexachloro-1,5,5a, 6,9a-hexahydro-6,9-methano-2,4,3-benzo-dioxyanthiepin-3-oxide) kg-' food dry weight, equivalent to an ultra-low dosis of 15 ng kg-' fish d-', were investigated by means of light and electron microscopy Observations on liver alterations were quantified by morphometric analysis Livers show enlargement of the nucleolus, increase in number and size of both Golgi flelds and rough endoplasmic reticulum (ER) lamellae, as well as proliferation of peroxisomes and lysosomes. Taken together, these alterations represent the morphological equivalent of a general stimulation of hepatic metabolism. Proliferation of the smooth ER is indicative of the onset of biotransformation processes under the influence of food-borne endosulfan. Further pathological processes in the liver were evident by glycogen and lipid depletion, invasion of phagocytic macrophages, and accun?ulation of myelinated bodies in endothehal cells of hepatic sinusoids. In the intestinal tract, exposure to endosulfan is associated with a complete lack of chylomicrons in the epithelia1 lining, w h~c h indicates disturbance of intestinal absorption. The reaction of the gut epithelium also included considerable distension of the intercellular space and an elevated number of lysosomal inclusions in enterocytes. An increased rate of mucous cell precursors was detectable, and rnacrophages were numerous. Results are consistent with endosulfan resorption by the intestinal epithelium and the coexistence of gut and liver ultrastructural changes at extremely low doses. Thus, the substantiation of patholog~cal alterations In organs sequentlally in contact with toxicants appears useful as a biomarker of pollutant exposure and effect. With regard to a chemical spill into the Rhine river at Basel, Switzerland, in November 1986, endosulfan, as a component of the mixture of toxic substances, may well have contributed to the overall toxicity of the chemicals released during the accident and the subsequent fish kill, less as a toxicant in itself than as a stimulant for the toxicity of other xenobiotics.

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Section: Discussionmentioning

confidence: 99%

Ultrastructural alterations in the liver and intestine of carp Cyprinus carpio induced orally by ultra-low doses of endosulfan

Braunbeck¹,

Appelbaum²

1999

Dis. Aquat. Org.

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“…This may in part be due to the high mortalities seen in fish exposed to PB (22). However, some investigations have shown induction of various cytochrome P450 monooxygenases by PB-like compounds (23)(24)(25)(26)(27)(28). Others suggest that fish cytochrome P450 may be refractory to induction by PB-like compounds (22, 29 -32) despite the presence of CYP2B-related genes that have been detected in rainbow trout (31,33) and scup liver (34).…”

mentioning

confidence: 89%

Phenobarbital Induction of Gene Expression in a Primary Culture of Rainbow Trout Hepatocytes

Sadar

Ash

Sundqvist

et al. 1996

Journal of Biological Chemistry

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In mammals, phenobarbital (PB) is an in vivo inducer of the cytochrome P4502B (CYP2B) family, whereas in teleosts PB induction of cytochrome P450 is unclear. We show that teleost cytochrome P4502K1 (CYP2K1) protein levels and 7-pentoxyresorufin-O-deethylase activity were not induced by exposure of primary cultures of rainbow trout hepatocytes to PB. Instead, cytochrome P4501A1 (CYP1A1) gene expression was strongly induced by PB, based upon observations of marked increases in CYP1A1 mRNA, CYP1A1 protein, and 7-ethoxyresorufin-O-deethylase activity. In accordance with these data we provide a temporal study employing antibodies for the aromatic hydrocarbon (Ah) receptor that showed an increase in Ah receptor in nuclear extracts prepared from cells exposed to PB. Employment of the electrophoretic mobility shift assay (EMSA) showed PB to cause activation or "transformation" of the Ah receptor in nuclear extracts. Studies employing actinomycin D and cycloheximide indicated that PB induction of CYP1A1 was regulated at both the transcriptional and post-transcriptional levels. Nuclear run-off experiments confirm that PB causes an increase in CYP1A1 transcription. Inhibition of protein synthesis led to the superinduction of CYP1A1 mRNA, suggesting the regulation of teleost CYP1A1 may involve a labile repressor protein. These findings suggest that PB induction of the CYP1A1 gene involves the Ah receptor and is via transcriptional activation.

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“…In both mammals (Gupta & Gupta 1979, Tyagi et al 1985 and fish (Jensen et al 1991) endosulfan has been shown to function as a phenobarbital-type inducer of cytochrome P-450. In general, fish have repeatedly been shown not to respond to induction by phenobarbital-type compounds ( G o k s~y r et al 1987, Kleinow et al 1987, Gooch et al 1989, Winston et al 1989), although they express corresponding cytochrome P-450 IIB genes (Elskus & Stegeman 1989, Stegeman 1989, Miranda et al 1990; for nomenclature, see Nebert et al 1991).…”

Section: Introductionmentioning

confidence: 99%

Cytological alterations in the liver of rainbow trout Oncorhynchus mykiss after prolonged exposure to low concentrations of waterborne endosulfan

Arnold¹,

Hj²,

Braunbeck³

1996

Dis. Aquat. Org.

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ABSTRACT-In order to elucidate sublethal cytopathological alterations in hepatocytes, mature male rainbow trout Oncorhynchus mykiss were exposed to 1, 10. 50, and 100 ng I-' technical grade endosulfan (ThiodanTM, 70% a-and 30 % P-isomers) for 28 d. Whereas stereological parameters, i.e. relative volumes and numbers of cell organelles, were unaffected, qualitative ultrastructural alterations were detectable from 10 ng I-' endosulfan. The No-Observed-Effect Concentration (NOEC) for cytological alterations was determined to be 1 ng I-' endosulfan, i e 3 orders of magnitude below the LC,, value Cytological effects that were probably of an adaptive nature included proliferation of SER and circular arrays of RER indicating induction of mixed-function oxygenases (MFO) as well as an increase in lysosomal elements at 50 and 100 ng I-' endosulfan, probably due to enhanced cellular turnover In addition, at 250 ng 1-' endosulfan, degenerative effects such as dilation of intermembranous spaces in mitochondria, deformation of mitochondria, myelin formation in peroxisomes and cytoplasm, and vesiculation and dilation of RER cisternae were observed. Although there was no indication of specific sublethal modes of toxic action except for MFO induction, the present study indicates that endosulfan has toxic impacts at concentrations of environmental relevance.

show abstract

Response of xenobiotic metabolizing enzymes in rainbouw trout (Oncorhynchus mykiss) to endosulfan, detected by enzyme activities and immunochemical methods

Cited by 33 publications

References 28 publications

Ultrastructural alterations in the liver and intestine of carp Cyprinus carpio induced orally by ultra-low doses of endosulfan

Ultrastructural alterations in the liver and intestine of carp Cyprinus carpio induced orally by ultra-low doses of endosulfan

Phenobarbital Induction of Gene Expression in a Primary Culture of Rainbow Trout Hepatocytes

Cytological alterations in the liver of rainbow trout Oncorhynchus mykiss after prolonged exposure to low concentrations of waterborne endosulfan

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