Acute exposure of rabbits to diphenyl diselenide: a toxicological evaluation.
The simple organoselenium compound diphenyl diselenide (PhSe)(2) is a promising new pharmacological agent. However, few toxicological evaluations of this molecule have been reported. We evaluated the effects of acute administration of (PhSe)(2) on toxicological parameters in rabbits. Adult New Zealand rabbits were exposed to (PhSe)(2) (5-500 micromol kg(-1) , intraperitoneally) once a day for 5 days. Exposure to 500 micromol kg(-1) caused 85% mortality. Exposure to 50 micromol kg(-1) of (PhSe)(2) increased the glutathione levels in the hippocampus, kidney, heart, muscle and blood, whereas lipoperoxidation (TBARS) decreased in the cerebellum and kidney after exposure to 5 micromol kg(-1) . The activity of glutathione peroxidase increased in the heart and muscle of rabbits treated with 50 micromol kg(-1) of (PhSe)(2) and glutathione reductase activity was reduced in the cerebellum, cerebral cortex and kidney. Treatment with (PhSe)(2) reduced the activity of δ-aminolevulinate dehydratase in the hippocampus and increased this activity in the heart, but did not alter the activity of complexes I and II of the respiratory chain in the liver and brain. Hepatic and renal biochemical and histological parameters were not modified by (PhSe)(2) and apoptosis was not detected in these tissues; however, the hepatic cells tended to accumulate fat vacuoles. These results indicated that acute toxicology to (PhSe)(2) in rabbit is dependent on the dose, which should motivate further experiments on the therapeutic properties of this compound.
Straliotto
Marcos Raniel
MR
Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis, SC, 88040900, Brazil.
Mancini
Gianni
G
de Oliveira
Jade
J
Nazari
Evelise Maria
EM
Müller
Yara Maria Rauh
YM
Dafre
Alcir
A
Ortiz
Susana
S
Silva
Edson Luiz
EL
Farina
Marcelo
M
Latini
Alexandra
A
Rocha
João Batista Teixeira
JB
de Bem
Andreza Fabro
AF
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000633:toxicity*; D001555:Benzene Derivatives / Q000378:metabolism* / Q000633:toxicity*; D001921:Brain / Q000187:drug effects; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D009132:Muscles / Q000187:drug effects; D016566:Organoselenium Compounds / Q000378:metabolism* / Q000633:toxicity*; D018384:Oxidative Stress; D000623:Porphobilinogen Synthase / Q000378:metabolism; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D023382:Toxicity Tests, Acute
D000975:Antioxidants; D001555:Benzene Derivatives; D016566:Organoselenium Compounds; D017392:Thiobarbituric Acid Reactive Substances; C061132:diphenyldiselenide; D003404:Creatinine; D005979:Glutathione Peroxidase; D000623:Porphobilinogen Synthase