Protective effects of pyrrolidine dithiocarbamate on myocardium apoptosis induced by adriamycin in rats.
BACKGROUND
Effects of pyrrolidine dithiocarbamate (PDTC) on programmed cell death are controversial. It is unclear if PDTC has the protective effects on myocardial apoptosis induced by adriamycin (ADR) in rats. The present study was undertaken to study the protective effects of pyrrolidine dithiocarbamate (PDTC) on myocardium apoptosis induced by adriamycin (ADR) in rats and its mechanisms.


METHODS
Forty male Wistar rats were randomly divided into five groups: control, ADR, ADR+PDTC 50 mg/kg, ADR+PDTC 100 mg/kg and ADR+PDTC 200 mg/kg group. Myocardial apoptosis was detected by electron microscopic examination and TUNEL assay. Myocardium p53 gene expression was examined by RT-PCR analysis. Location and distribution of p53 was observed by immunohistochemical assay. Myocardial expression of p53 protein was assessed by Western blot analysis. Activity of NF-kappaB was evaluated by Electrophoretic Mobility Shift Assay.


RESULTS
Myocardial apoptotic index, expression of p53 mRNA, expression of p53 protein and the binding activity of NF-kappaB decreased significantly in ADR+PDTC groups compared with ADR group. All these change were significantly correlated with dose of PDTC.


CONCLUSIONS
PDTC has preventive effects on myocardial apoptosis induced by ADR, which is probably associated with inhibiting binding activity of NF-kappa B and further regulating apoptosis-related gene expression and translation, and inhibiting myocardial apoptosis.
Li
Hongli
H
Department of Cardiology, Shanghai Jiaotong University Affiliated First People's Hospital, 85 Wujin Road, Shanghai, 200080, PR China.
Gu
Hongyue
H
Sun
Baogui
B
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D016158:Genes, p53 / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000473:pathology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013859:Thiocarbamates / Q000494:pharmacology*
D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D004317:Doxorubicin