Protective effects of silymarin against doxorubicin-induced toxicity.
OBJECTIVE
The aim of the present study was to investigate the effect of silymarin on doxorubicin-induced toxicity to the rat kidney, heart, and liver.


METHODS
A single dose of 10 mg/kg doxorubicin was injected intraperitoneally (ip) in the doxorubicin group. The silymarin group received silymarin (100mg/kg) every other day. In the doxorubicin + silymarin group, silymarin was injected ip at 100 mg/kg dose for 5 days before doxorubicin administration (10 mg/kg, single ip injection) and then continued daily thereafter until euthanization. On the seventh day after doxorubicin injection, eight animals from each group were decapitated and liver and heart samples were obtained. The remaining eight animals of each group continued to receive silymarin every other day, till euthanized on the twenty first day. Serum was separated for determination of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO), creatinine, urea, AST, ALT, lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK) activities. Histopathological and electron microscopic examinations of heart, kidney and liver sections were also performed.


RESULTS
Doxorubicin caused a significant increase in serum NO levels compared to controls. Silymarin pretreatment group lowered these. Histopathological and electron microscopic examinations of kidney, heart, and liver sections showed doxorubicin to cause myocardial and renal injury which was levv evident in silymarin treated rats.


CONCLUSIONS
Results of the present study indicate that silymarin significantly protected doxorubicin-induced toxicities to the rat kidney, heart, and liver, thus suggesting its administration as a supportive care agent during anti-cancer treatment featuring doxorubicin.
Department of Pediatric Oncology, Adnan Menderes University, School of Medicine, Aydin, Turkey. rececen@adu.edu.tr
E
E
Cecen
T
T
Dost
N
N
Culhaci
A
A
Karul
B
B
Ergur
M
M
Birincioglu
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D004317:Doxorubicin / Q000009:adverse effects / Q000633:toxicity*; D005260:Female; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012838:Silymarin / Q000494:pharmacology*
D000970:Antineoplastic Agents; D012838:Silymarin; D009569:Nitric Oxide; D004317:Doxorubicin