Protective role of granulocyte colony-stimulating factor against adriamycin induced cardiac, renal and hepatic toxicities.
Adriamycin (ADR) causes dose-dependant toxicities in heart, liver and kidneys via inducing the peroxidative alterations in organ tissues. Recent studies showed that the granulocyte colony-stimulating factor (G-CSF) exerts beneficial effects on heart, liver and kidney injuries induced by different pathological conditions. We hypothesize that G-CSF have a protective effect on ADR induced cardiac, renal and hepatic toxicities by inhibiting the peroxidative alterations in organ tissues. Wistar rats were randomly divided into control, ADR, ADR+phosphate buffered saline (PBS) and ADR+G-CSF group (n=16 in each group). ADR was administered intraperitoneally every other day at the dose of 2.5 microg/kg each time per rat (total six times of injection during 2 weeks). Rats in the ADR+G-CSF group were injected subcutaneously with G-CSF at the dose of 50 microg/(kg day) (for 8 consecutive days). After 8 weeks, the serum and urine biochemistry variables were determined. The malondialdehyde (MDA) level and the glutathione (GSH) content in the heart, the liver and the kidney tissues were measured. ADR caused significant cardiac, renal and hepatic toxicities indicated by the serum and urine biochemistry variables. The tissue MDA level in the heart, kidney and liver in rats treated with ADR were markedly elevated, while the GSH content in these tissues were significantly reduced. G-CSF administration palliated the cardiac, renal and hepatic toxicities. Notably, G-CSF induced significant reduction of MDA level and increase of GSH content in the heart, kidney and liver tissues. This study suggests that G-CSF play an overall protective effect on ADR-induced toxicities in heart, liver and kidneys and the inhibition of tissue peroxidative alterations might contribute to this beneficial effect.
Department of Cardiology, Hangzhou First Municipal Hospital and Hangzhou Hospital, Nanjing Medical University, Huan-sha Road 26, Hangzhou 310006, China. beckhxw007@yahoo.com.cn
Xu-Wei
XW
Hou
Yu
Y
Jiang
Li-Fang
LF
Wang
Hai-Ying
HY
Xu
Hong-Min
HM
Lin
Xiu-Ying
XY
He
Jian-Jun
JJ
He
Sheng
S
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001774:Blood Chemical Analysis; D056486:Chemical and Drug Induced Liver Injury; D004317:Doxorubicin / Q000633:toxicity*; D004336:Drug Antagonism; D005978:Glutathione / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016482:Urinalysis
D000970:Antineoplastic Agents; D008315:Malondialdehyde; D004317:Doxorubicin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005978:Glutathione