Abstract

The effects of TCDD on normal and iron-deficient mice fed a casein-based diet were compared. Liver damage, porphyria, and thymic atrophy were studied in C57B1/6J mice, chloracne and liver damage in the HRS/J strain. Sequential pathologic changes also were studied in C57B1/6J mice fed laboratory chow and treated with TCDD (25 μg/kg/week). Steatosis was present by Day 4; cell swelling, necrosis, and disorganization of the acinar architecture followed with maximal effects from weeks 4 to 8. Widespread necrosis of liver and cholangiofibrosis were late changes. The disturbance of porphyrin metabolism was localized to zone III. Mice fed a low iron diet supplemented with 0.05% w w Fe and treated with TCDD (25 μg/kg/week × 12 weeks) developed porphyria after 15 weeks; venesected mice not supplemented with iron had not developed porphyria by 20 weeks. In general, an interaction was noted between TCDD and iron as judged by the rapidity of onset and severity of the porphyria. Iron-deficient and iron-supplemented groups of C57B1/6J mice received 37.5 μg/kg of TCDD. After 5 days there was an equal decrease in thymus weight in both groups of animals but histologic evidence of liver damage was less in the low iron mice. TCDD (45 μg/kg) was applied to the skin of iron-deficient and iron-supplemented hairless (HRS/J) mice. After 3 weeks chloracne developed irrespective of iron status; liver porphyrin was normal in the low iron animals but increased 100-fold in iron-supplemented mice in which histologic damage was also more severe. In general, iron deficiency did not decrease the activity of the hepatic mixed-function oxygenase systems. We conclude that iron deficiency protects against porphyria due to TCDD but that protection by iron deficiency against histologic damage to the liver is incomplete. In contrast, iron deficiency did not affect thymic atrophy or chloracne caused by TCDD.

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