Reduction of hepatic and renal nonprotein sulfhydryl content and increased toxicity of rubratoxin B in the Syrian hamster and Mongolian gerbil.
Studies were undertaken to determine if the toxicity and pathology of rubratoxin B, a nephrotoxic and hepatotoxic mycotoxin, could be altered by increasing or decreasing the tissue concentrations of nonprotein sulfhydryls in the liver and kidneys. Rubratoxin B dissolved in DMSO was administered ip to weanling male Syrian hamsters and Mongolian gerbils at doses of 0.4 mg/kg and 2.0 mg/kg, respectively. Rubratoxin B caused a 70% decrease in hepatic and a 60% decrease in renal cortical nonprotein sulfhydryl (NPSH) concentration, an index of tissue reduced glutathione concentration, in both species. Treatment with cysteine prior to rubratoxin B administration did not greatly alter the decreases in NPSH concentration, but did decrease the severity of renal lesions. Treatment with diethyl maleate prior to rubratoxin B administration caused an 80% reduction in hepatic and a 70% reduction in renal NPSH concentration, which was prolonged by rubratoxin B treatment. The incidence and severity of renal lesions was increased in rubratoxin B-treated hamsters and gerbils given diethyl maleate compared to animals given rubratoxin B alone. Additionally, hepatic lesions were seen in hamsters and were more frequent and severe in gerbils that were treated with diethyl maleate prior to rubratoxin B dosing compared to animals given rubratoxin B alone. Renal and hepatocellular NPSH concentration appears to decrease during rubratoxin B toxicosis in the hamster and gerbil, and appears to be contributory in lesion development, since lesions in the liver and kidneys were more severe in animals in which NPSH concentrations were reduced by treatment with diethyl maleate.
Engelhardt
J A
JA
Department of Veterinary Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907.
Carlton
W W
WW
Carlson
G P
GP
Hayes
A W
AW
D000818:Animals; D006224:Cricetinae; D003545:Cysteine / Q000633:toxicity; D005849:Gerbillinae; D007668:Kidney / Q000187:drug effects*; D007684:Kidney Tubules / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D008298:Maleates / Q000633:toxicity; D008647:Mesocricetus; D009183:Mycotoxins / Q000633:toxicity*; D009336:Necrosis; D013438:Sulfhydryl Compounds / Q000032:analysis*
D008298:Maleates; D009183:Mycotoxins; D013438:Sulfhydryl Compounds; C100297:rubratoxins; C014476:diethyl maleate; D003545:Cysteine