Toxicity and evidence for metabolic alterations in 2,3,7,8-tetrachlorodibenzo- p-dioxin-treated guinea pigs fed by total parenteral nutrition

Abstract

The effect of total parenteral nutrition (TPN) on the toxicity of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) in male, Hartley-strain guinea pigs was determined. At a single dose of 2 μg TCDD/kg, TPN-fed guinea pigs maintained body weight at a level which was slightly, but consistently, below that of the TPN-fed control animals. However, despite the sustenance of body weight, TCDD-treated animals died or were sacrificed due to morbidity between Days 8 and 24 following treatment. Approximately 50% of this group demonstrated a profound loss of body weight within a few days prior to death or sacrifice. With the exception of the pattern of weight loss, the signs of toxicity in the TPN-fed, TCDD-treated animals were strikingly similar to those observed in TCDD-treated guinea pigs fed ad libitum. Although livers from TCDD-treated, TPN-fed animals demonstrated increased content of lipid and cytochrome P-450, this tissue appeared to be morphologically and functionally comparable to that from TPN-fed controls. Of the blood chemistry examined, only the serum concentrations of 3,5,3′-triiodothyronine were significantly decreased in the treated animals fed by TPN. Results were also compared to TCDD-treated guinea pigs fed ad libitum and respective pair-fed controls. Many of the physiological and biochemical responses observed in animals fed ad libitum following TCDD treatment could be explained by a decrease in food consumption. This study demonstrated that although food consumption clearly accounts for the major effect of TCDD on body weight loss in guinea pigs fed ad libitum, additional physiological and/or biochemical alterations occurred which also contribute to body weight loss, other signs of toxicity, and subsequent lethality.