Modulation of TCDD-induced wasting syndrome by portocaval anastomosis and vagotomy in Long-Evans and Han/Wistar rats.
Portocaval anastomosis and vagotomy operations were performed in Long-Evans (L-E) and Han/Wistar (H/W) rats to elucidate the mechanism of anorexia induced by TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). TCDD-sensitive L-E rats were given a sublethal (5 micrograms/kg) or a lethal dose (20 micrograms/kg) by gavage 5-8 weeks after portocaval anastomosis. TCDD-resistant H/W rats were given a nonlethal dose (500 or 7200 micrograms/kg). The shunt operation did not reduce lethality from TCDD. The effect on wasting of the marginally toxic dose of 5 micrograms/kg in L-E rats was potentiated by the portocaval operation, and the lethal dose was effective in both shunted and sham-operated L-E rats. TCDD failed to decrease food intake and body weight in shunted rats of H/W strain at either dose level though it did so in sham-operated controls. The lack of effect may be due to the already reduced weight of shunted rats at the time of TCDD dosing. TCDD anorexia was not explained by changes in histamine or serotonin (5-HT) turnover in the brain. Vagotomy did not influence lethality after TCDD, although reduction in food intake was somewhat blunted in H/W rats. The results seem to indicate that the anorectic effect of TCDD is modified when portal blood bypasses the liver. The mechanisms remain to be elucidated in detail, but the results do not favor the role of liver as the only or the major initiator of TCDD anorexia. Little evidence was found to support a crucial role of vagal afferent input.
Tuomisto
J
J
Department of Toxicology, National Public Health Institute, Kuopio, Finland.
Andrzejewski
W
W
Unkila
M
M
Pohjanvirta
R
R
Linden
J
J
Vartiainen
T
T
Tuomisto
L
L
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004435:Eating / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011167:Portacaval Shunt, Surgical; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D014628:Vagotomy; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology*
D000072317:Polychlorinated Dibenzodioxins; D012701:Serotonin; D006632:Histamine