Toxicity and irreversible binding of two DDT metabolites —3‐methylsulfonyl‐DDE and o,p'‐DDD‐in adrenal interrenal cells in birds

Abstract

The toxicity and the metabolism dependent irreversible binding of the lipophilic DDT metabolites 3‐methylsulfonyl DDE (MeSO2 DDE) and o,p DDD in the adrenal gland of the chicken were examined As determined by histopathology, vacuolar degeneration and pycnosis of adrenal interrenal cells occurred 4 d after injection of a single dose of either compound (0 25 mmol/kg, 80–100 mg/kg body weight) to 6‐d old chicken In addition, o,p DDD, but not MeSO2 DDE, induced fatty degeneration of the liver According to autoradiography, irreversibly bound radioactivity was present in the interrenal cells after injection of the 14C‐labeled compounds into the air sacs of eggs Both DDT metabolites were also irreversibly bound to protein after incubation with adrenal 300 g supernatant in vitro, with apparent Km values of 2 0 and 8 3 μM for MeSO2 DDE and o,p DDD, respectively The irreversible binding in vitro was inhibited by metyrapone, SKF 525A, and carbon monoxide, suggest ing a cytochrome P450‐dependent metabolic activation to reactive intermediates Addition of glutathione to the incubations reduced the irreversible binding of MeSO2‐[14C]DDE significantly, whereas the irreversible binding of o,p [14C]DDD remained un changed The results indicate that MeSO2‐DDE and o,p DDD are adrenocorticolytic following an adrenal P450‐dependent met abolic activation in the chicken Experiments with embryonated eggs from common eider and domestic duck demonstrated that MeSO2 DDE and o,p DDD are also metabolically activated and irreversibly bound to adrenal tissue in embryos of these species

Experimentally reducing corticosterone mitigates rapid captivity effects on behavior, but not body composition, in a wild bird

“…Mitotane inhibits CORT production by suppressing mitochondrial steroid 11β-hydroxylase and cholesterol side-chain cleavage activity in the zona fasciculata of the adrenals (Sanderson, 2006). Because it is metabolically activated by an adrenal-specific cytochrome P450 (Jonsson et al, 1994), mitotane has been found to be quite selective in its effects - for example, an earlier study found that mitotane had no effects on testis size or testosterone titers in male house sparrows (Breuner et al, 2000). However, there are documented instances of mitotane treatment causing liver damage (Nagai et al, 1999), which can lead to hepatocyte proliferation (Sell, 2003).…”

“…Mitotane is metabolically activated by an adrenal-specific cytochrome P450 (Jonsson et al, 1994); in this active form, it blocks cyctochrome P450-mediated reactions, causing selective necrosis of adrenocortical tissue and reducing glucocorticoid production (Maher et al, 1992). Half of the birds (n=10) received injections of mitotane, and the other half (n=10) a vehicle control.…”

Adrenocorticotrophin‐ and cyclic adenosine 3′,5′‐monophosphate‐stimulated cortisol secretion in interrenal tissue of rainbow trout exposed in vitro to DDT compounds

“…There are no data available, however, on the metabolism of DDT in fish. Two metabolites of DDT, methysulfonyl‐DDE and o,p ′‐DDD, have adrenolytic effects in some species of birds and mammals [6,7]. The teleost interrenal tissue, enriched with lipids originating from the steroid precursor cholesterol, may be particularly vulnerable to lipophilic xenobiotics such as DDT, as has been documented for mammalian adrenals [6].…”

“…The biochemical site of action of o,p ′‐DDD in this species has been located at a step following the generation of cAMP [23], specifically the conversion of cholesterol into pregnenolone and the 11 β‐hy‐droxylation of 11‐deoxycortisol into cortisol, two intramito‐chondrial steps [24]. More recently, o,p ′‐DDD and other DDT compounds such as p,p ′‐DDD, p,p ′‐DDT, and MeSO 2 ‐DDE have been studied in other mammals (guinea pig, mink, otter, gray seal) and in birds (chicken, domestic duck, and common eider) [6,7,25,26]. These studies demonstrated the covalent binding of o,p ′‐DDD, p,p ′‐DDD, and p,p ′‐DDT to the adrenal cortical cells and the subsequent activation of the compound into a reactive intermediate that binds and inhibits the 11 β‐hydroxylase [6,26].…”

“…These studies demonstrated the covalent binding of o,p ′‐DDD, p,p ′‐DDD, and p,p ′‐DDT to the adrenal cortical cells and the subsequent activation of the compound into a reactive intermediate that binds and inhibits the 11 β‐hydroxylase [6,26]. Degeneration of the adrenal cortex and mitochondria were observed in the zona fasciculata and reticularis; however, species differences exist in the DDT compounds and the type of effects generated by these organoch‐lorinated chemicals [6,7,25,27–29].…”