Corticosterone Modulates Acute Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-1 dioxin (TCDD) in Male Sprague--Dawley Rats

Corticosterone Modulates Acute Toxicity of 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) in Male Sprague-Dawley Rats.GORSKI, J. R., ROZMAN, T.,GREIM, H., AND ROXMAN, K. (1988). Fundam Appl. Toxicol 11, 494-502.Bilateral adrenalectomy or adrenal demedullation was performedon male Sprague-Dawley rats by established surgical techniques.Subsequently, the dose-response (mortality and mean time todeath) to TCDD was determined in adrenalecto-mized (10, 20,40 µg/kg TCDD ip in 95:5 corn oil: acetone) or demedullated(15, 30, 60 µg/kg TCDD) rats. Adrenalectomy drasticallyincreased mortality and greatly shortened mean time to deathafter dosing with TCDD. More importantly, adrenalectomized TCDD-treatedrats died 3 of hypoglycemic shock without losing much body weightConversely, adrenal demedullation had no effect on mortalityor mean time to death caused by TCDD when compared to non-demedullatedTCDD-treated controls. Thus, it was concluded that the factors)modulating the acute toxicity of TCDD resides in the adrenalcortex and not in the medulla. Administration of corticosterone(25 ngjµl in drinking water) to adrenalectomized ratsreturned the toxicity of TCDD to levels seen in nonadrenalectomizedrats suggesting that this hormone is another key 3 factor (inaddition to the thyroid hormones) in the modulation of the acutetoxicity of TCDD. Corticosterone supplementation (25, 50, or100 µg/) to nonadrenalectomized rats, or to thy- roidectomized-adrenalectomizedrats (25 µg/ml), resulted in no additional beneficialeffect indicating that a factoids) other than thyroid hormonesand corticosterone is also involved in the 14 acute toxicityof TCDD