Elevated plasma corticosterone levels and histopathology of the adrenals and thymuses in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.
The relationship between thymic atrophy and plasma corticosterone levels was examined in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated, pair-fed and ad libitum-fed male Sprague-Dawley rats given a usually lethal (125 micrograms/kg) or non-lethal (25 micrograms/kg) dose of TCDD. At both dosages, corticosterone levels in TCDD-treated animals begun to rise as early as day 4 after treatment. At later time points corticosterone levels were 5-7 times higher in rats given the non-lethal dose, and 6-10 times higher in rats administered the lethal dose than the levels observed in ad libitum-fed controls. Corticosterone levels in control rats pair-fed to the lethal dose group (as a result of the severe reduction in feed intake) were similarly elevated as in TCDD-treated rats but this was not the case in pair-fed rats of the non-lethal TCDD dosage (due to an essentially unchanged feed intake). At both dosages, relative thymus weights of TCDD-treated rats started decreasing by day 4 and continued to decline for the most part of the study. Relative thymus weights of rats pair-fed to the non-lethal TCDD dosage were not different from ad libitum-fed rats. However, the decrease in relative thymus weights of rats pair-fed to the lethal TCDD dosage paralleled that of TCDD-treated rats with an apparent 8-day lag period. Morphologically, the thymus as well as the adrenal revealed differential changes in TCDD-treated rats from those observable in pair-fed rats. These results suggest that either TCDD exerts a direct effect on the thymus and the adrenals or it causes an additional stress (e.g., a metabolic stress) over and above the starvation stress, which may be responsible for the differential morphological changes in these glands.
Gorski
J R
JR
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Muzi
G
G
Weber
L W
LW
Pereira
D W
DW
Iatropoulos
M J
MJ
Rozman
K
K
D000311:Adrenal Glands / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004435:Eating; D008297:Male; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D003345:Corticosterone