Protective effects of N-acetylcysteine and selenium against doxorubicin toxicity in rats.
To investigate the neutralizing effect of N-acetylcysteine (NAC) and selenium (Se) against doxorubicin (DOX) toxicity in rats, NAC (140 mg/kg, p.o.) and Se (0.5 mg/kg, p.o.) were administered for 2 days before DOX injection and then 3 times a week. Cell viability and the level of lipid peroxidation were examined in cultured-rat astrocytes. Severe morphologic changes in the kidney of DOX group; thickening of Bowmans capsule, presence of multifocal tubular casts were observed, but not in the other treated groups. Vacuoles in some hepatic cells and focal aggregation of stellate macrophages were also detected in DOX group, but not in the other treated groups. However, the severe inhibition of spermatogenesis was found in all treated groups. The cell viability of DOX (10 mg/ml) treated group and NAC (5 mM) or Se (0.001 mg/ml) combined-treated group was 52.5-/+2.0 %, 85.3-/+4.5 % and 75.5-/+1.6 %, respectively. In MDA (malondialdehyde) assay, the level of lipid peroxidation on DOX (10 mg/ml), NAC (5 mM) and Se (0.001 mg/ml) was 0.77-/+0.06, 0.35-/+0.06 and 0.54-/+0.11 nmol/mg protein, respectively. Thus, it is known that NAC and Se have protective effects in kidney and liver but not in the testes. Morphological change was not detected in brain and heart in all groups for experiment period. From this in vitro study, it is known that NAC and Se protect well the astrocytes against DOX induced-cell damage.
Park
Eun-sung
ES
Department of Veterinary Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, San 56-1, Shilim-dong, Gwanak-gu, Seoul 151-742, Korea.
Kim
Sun-don
SD
Lee
Min-hye
MH
Lee
Heung-shik S
HS
Lee
In-se
IS
Sung
Je-kyung
JK
Yoon
Yeo-sung
YS
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013090:Spermatocytes / Q000166:cytology / Q000187:drug effects / Q000473:pathology
D004317:Doxorubicin; D000111:Acetylcysteine