Limited role of the intestinal microflora in the nephrotoxicity of hexachloro-1,3-butadiene in rats.
The nephrotoxicity of hexachlorobutadiene has been investigated in germ-free rats and compared to conventional rats that have a normal intestinal microflora. Presynthesized mercapturate intermediates of hexachlorobutadiene, the glutathione and the cysteine S-conjugate, were also administered. Germ-free rats appeared to be slightly more susceptible to hexachlorobutadiene by judging the extent of morphological changes compared to conventional ones. A similar response was also observed after treatment with the glutathione and cysteine S-conjugates. However, no significant difference between germ-free and conventional animals was monitored in the extent of elevation of blood urea nitrogen and plasma creatinine after treatment with hexachlorobutadiene or the glutathione and the cysteine S-conjugates. The urinary excretion of marker enzymes was monitored and showed that gamma-glutamyl transferase was significantly more increased in the germ-free rats when treated with the cysteine S-conjugate. In addition, no difference in the rate of glutathione conjugation of hexachlorobutadiene was measured between the two groups. Although a tendency toward a protective effect by the presence of an intestinal microflora was observed, the role of the intestinal microflora in detoxifying hexachlorobutadiene seems to be of limited importance in rats.
Wallin
A
A
Department of Toxicology, Karolinska Institute, Stockholm, Sweden.
Ormstad
K
K
Midtvedt
T
T
D000818:Animals; D002070:Butadienes / Q000378:metabolism / Q000633:toxicity*; D005856:Germ-Free Life; D005982:Glutathione Transferase / Q000502:physiology; D007422:Intestines / Q000382:microbiology*; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D051381:Rats
D002070:Butadienes; C001335:hexachlorobutadiene; D005982:Glutathione Transferase