Ellu Manzoor

Effect of 2,3,7,8-tetrachlorodibenzoy-p-dioxin on the hepatic 7-ethoxyresorufin O-deethylase activity in four rodent species

Temporal and dose-related effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic 7-ethoxyresorufin O-deethylase (EROD) activity were investigated in young male Hartley guinea pigs, Sprague-Dawley rats, C57Bl/6 mice, DBA/2 mice and Golden Syrian hamsters. Animals were terminated 1, 7, 14, 28, 56 and 112 days after the administration of a single i.p. dose of TCDD. The maximal induction of EROD activity, at doses producing a similar toxic and limited lethal effect in all species/strains, was 42-, 18-, 7- and 3-fold in rats, DBA/2 mice, C57Bl/6 mice and guinea pigs, respectively. No treatment-related induction of EROD activity was observed in hamsters. Generally, maximal induction occurred 1-4 weeks after injection in all species. The guinea pig alone maintained the same magnitude of induction of EROD activity throughout the study. Observed toxic effects, i.e., lethality, loss of body weight gain, liver enlargement and thymic atrophy, did not correlate with the TCDD-induced hepatic EROD activity. The obtained results suggest that the fold induction of cytochrome P450 1A1 activity is not a critical event for the expression of the lethal effect of TCDD in rodents.

Effects of combinations of PCDDs/PCDFs given to Sprague-Dawley rats

Abstract Groups of male Sprague-Dawley rats received 1,2,3,7,8-pentaCDD (PeCDD), 2,3,4,7,8-pentaCDF (PeCDF) and octaCDD (OCDD) alone or in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a single oral dose. Four weeks later the rats were sacrificed and body weight gain, relative liver and thymus weights as well as hepatic and renal vitamin A, hepatic cytochrome P-450/448, EROD and UDPGT, were measured. Hepatic vitamin A levels were decreased by all congeners including OCDD but no additive effects were evident in the groups receiving the TCDD/non TCDD combinations. The TCDD induced EROD activity was not further induced by simultaneous exposure to PeCDD, PeCDF or OCDD. PeCDD and PeCDF but not OCDD increased the TCDD-induced UDPGT activity slightly.

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the lactating rat on maternal and neonatal vitamin A status and hepatic enzyme induction: a dose-response study

Abstract Young male Sprague-Dawley rats exposed to TCDD via mothers milk show induced hepatic ethoxyresorufin O -deethylase (EROD) activity at doses where no effects on food consumption, growth and organ weights are observable, while effects on tissue vitamin A contents occur concurrent with these toxic symptoms. In contrast to the dams, offspring also show decreasing vitamin A contents of the lung in response to TCDD-exposure.

TCDD and 2,3,4,7,8-PeCDF temporal interaction of vitamin A depletion and hepatic enzyme-inducton in the rat

Abstract Male Sprague-Dawley rats received 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,7,8-pentachlorodibenzofuran or a combination of these two congeners. The effects on weight, relative organ weights, hepatic, renal, pulmonary vitamin A levels and hepatic enzyme induction were measured.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced alterations in the vitamin A homeostasis and in the 7-ethoxyresorufin O-deethylase (EROD)-activity in Sprague-Dawley rats and Hartley guinea pigs

Abstract Data obtained in this study show that there is a correlation between toxic effects of TCDD and the effect on hepatic vitamin A storage. No such correlation was found for renal and serum vitamin A nor for hepatic EROD-induction.

Interaction of 6-methyl-1,3,8-trichlorodibenzofuran with tcdd-induced vitamin A reduction

Abstract 6-Methyl-1,3,8-trichlorodibenzofuran (MCDF) have been shown to inhibit TCDD-induced enzymeinduction both in rat and in cell culture. MCDF, alone or together with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was administered to rats in order to investigate the ability of MCDF to reduce TCDD-induced vitamin A depletion. High doses of MCDF induced vitamin A-depletion, but no inhibitory effect on TCDD-induced depletion was seen in this experiment.

“ED50” values for TCDD-induced effects on vitamin A in hartley guinea pigs, Sprague-Dawley rats, C57B1/6 mice and golden Syrian hamsters

Abstract In this four-week study, body and organ weights, and the vitamin A content of different organs were measured in guinea pigs, rats, mice and hamsters after exposure to TCDD. In all species, hepatic vitamin A reduction was the most sensitive parameter measured. However, in hamsters, reduced hepatic vitamin A appeared at much lower doses, relative to LD50, than in guinea pigs, rats and mice.