Renal toxicity of perchloroethylene and S-(1,2,2-trichlorovinyl)glutathione in rats and mice: sex- and species-dependent differences.
Suspensions of renal cells from rats and renal mitochondria from rats and mice were used to assess the sex and species dependence of acute toxicity due to perchloroethylene (Perc) and its glutathione conjugate S-(1,2,2-trichlorovinyl)glutathione (TCVG). A marked sex dependence in the acute cytotoxicity of both Perc and TCVG was observed: Perc caused significant release of lactate dehydrogenase (LDH) in isolated kidney cells from male but not female rats, and TCVG caused much more LDH release from male than female rat kidney cells. Assessment of toxicity in suspensions of isolated mitochondria from kidneys of male and female rats revealed a generally similar pattern of sensitivity, with mitochondria from males exhibiting significantly more inhibition of State 3 respiration and decrease of respiratory control ratio than mitochondria from females. Respiratory function in mitochondria from male and female mice, however, was also significantly inhibited by Perc or TCVG but exhibited little sex dependence in the degree of inhibition. Comparison with results from similar studies using the congener trichloroethylene and its glutathione conjugate suggested that Perc and TCVG are more potent nephrotoxicants. Neither Perc nor TCVG produced any significant effects on cytotoxicity or mitochondrial function in isolated hepatocytes from rats or in isolated liver mitochondria from rats or mice, suggesting that the liver is not a major acute target for Perc or its glutathione conjugate. Thus, many of the species-, sex-, and tissue-dependent differences in toxicity of Perc and TCVG that are observed in vivo are also observed in these in vitro models.
Lash
Lawrence H
LH
Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. l.h.lash@wayne.edu
Qian
Wei
W
Putt
David A
DA
Hueni
Sarah E
SE
Elfarra
Adnan A
AA
Sicuri
Anna Rita
AR
Parker
Jean C
JC
D000818:Animals; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000633:toxicity*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics; D013045:Species Specificity; D013750:Tetrachloroethylene / Q000633:toxicity*
D004785:Environmental Pollutants; C060857:S-(1,2,2-trichlorovinyl)glutathione; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D013750:Tetrachloroethylene