Induction of hepatic mixed function oxidase system by endosulfan in rats

Tyagi, S.; Singh, Yogendra; Srivastava, P. K.; Misra, U. K.

doi:10.1007/bf01607536

Cited by 16 publications

(7 citation statements)

References 12 publications

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“…Compared to experiments with mammals, however (oral dose in the range of 1 to 10 mg kg-', e.g. Tyagi et al 1984), the dosage applied in the present experiment, i.e. 0.5 pg kg-' food, equivalent to 15 ng kg-' fish d-', is extremely low and emphasizes the extraordinary susceptibility of fish not only to acute, but also to sublethal levels of endosulfan.…”

Section: Discussioncontrasting

confidence: 55%

“…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).…”

Section: Discussionmentioning

confidence: 99%

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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: Discussioncontrasting

confidence: 55%

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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“…Values are mean + SE from six animals. (Tyagi et al 1984). It has been reported that the toxicity of endosulfan is inversely related to quantity of dietary protein (Boyd et al 1970).…”

Section: Tablementioning

confidence: 99%

“…In contrast Agarval et al (1978) reported that endosulfan induced the activities of some mixed function oxidases. The toxicity of endosulfan has been inversely related to the quantity and quality of, the protein in the diets (Boyd et al 1970, Tyagi et al 1984. The reasons for the discrepancy in the reports of these workers is not clear.…”

mentioning

confidence: 99%

“…The reasons for the discrepancy in the reports of these workers is not clear. Recently we have reported that higher dose of endosulfan (7.5 mg/kg body weight) for fifteen days, significantly increased the hepatic mixed function oxidases in male rats (Tyagi et al 1984). We have thus re-examined the hepatic mixed function oxidases inducing capacity of endosulfan using actinomycin D which is an inhibitor of induced protein synthesis.…”

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Induction of cytochrome p‐450 and phosphatidylcholine synthesis by endosulfan in liver of rats : Effect of quality of dietary proteins

Tyagi

Sriram

Narayan

et al. 1985

Journal of Environmental Science and Health, Part B

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Administration of endosulfan significantly increased microsomal protein, cytochrome P-450 content and the activity of aminopyrine N-demethylase. Effect of endosulfan and actinomycin D either alone or together on microsomal protein, cytochrome P-450, NADPH cytochrome c reductase, aniline hydroxylase, aminopyrine N-demethylase, phosphatidylcholine content, incorporation of 3H-choline and 14C-methionine were studied in rats given amino acid deficient and supplemented diets. Administration of endosulfan significantly increased the above parameters in both the dietary groups, whereas administration of actinomycin D did not have any effect in rats fed supplemented diets, however, significant decrease in the PC and the incorporation of choline and methionine into PC of rats fed deficient diet were observed. A positive correlation in the effect of endosulfan on hepatic mixed function oxidase activity and hepatic phosphatidylcholine is observed.

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An assessment of the developmental, reproductive, and neurotoxicity of endosulfan

Silva

Gammon

2009

Birth Defects Research Pt B

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BACKGROUND: Endosulfan has been used for over 50 years. Although most analogs have been discontinued, endosulfan has less environmental persistence. Nevertheless, pressure groups are lobbying for a worldwide ban. The reasons are: possible rodent male reproductive toxicity, other endocrine effects and cancer; human epidemiology, and exposure studies; residues appearing in remote areas of the world, e.g., the Arctic. METHODS: The endosulfan toxicology database is described and risks of its use assessed. RESULTS: Endosulfan is an antagonist at the GABA A receptor Cl À ionophore in mammalian CNS. Rat acute toxicity is moderate, LD 50 5 48 (M) or 10 mg/kg/d (F), oral gavage; 130 (M), 70 mg/kg/d (F) dermal; LC 50 5 34.5 mg/L (M), 12.6 mg/L (F), inhalation. Critical NOELs for risk assessment: acute oral (gavage) 5 0.7 mg/kg/d (rabbit developmental); Subchronic oral (diet) 5 1.2 mg/kg/d (rat reproduction); Chronic oral (diet) 5 0.6 mg/kg/d. There were no acceptable dermal toxicity studies. The critical acute and subchronic inhalation NOELs 5 0.001 mg/L, chronic inhalation 5 0.0001 mg/L (estimated). Toxicity to rat sperm occurred at doses causing neurotoxicity. Endocrine effects, resulting from P450 oxygenase(s) induction, were reversible. Increased cancer, genotoxicity, or histopathology in rodents was not observed in any organ. Possible effects on brain biogenic amine levels were probably secondary. CONCLUSIONS: Epidemiology and rodent studies suggesting autism and male reproductive toxicity are open to other interpretations. Developmental/ reproductive toxicity or endocrine disruption occurs only at doses causing neurotoxicity. Toxicity to the fetus or young animals is not more severe than that shown by adults.

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Induction of hepatic mixed function oxidase system by endosulfan in rats

Cited by 16 publications

References 12 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

Induction of cytochrome p‐450 and phosphatidylcholine synthesis by endosulfan in liver of rats : Effect of quality of dietary proteins

An assessment of the developmental, reproductive, and neurotoxicity of endosulfan

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