Anticarcinogenic effect of brucine in diethylnitrosamine initiated and phenobarbital-promoted hepatocarcinogenesis in rats.
We evaluated the effects of brucine on N-nitrosodiethylamine (DENA)-induced hepatocarcinogenesis in rats. Initiation of hepatocarcinogenesis was done by intraperitoneal injection of diethylnitrosamine (DENA) followed by promotion with phenobarbital. The rats were exposed to dietary brucine for 4 weeks prior to initiation, and the treatment was continued for 22 consecutive weeks. Brucine decreased the incidence, total number, multiplicity, size and volume of preneoplastic hepatic nodules in a dose-dependent manner. Administration of DENA induced hepatocellular carcinoma (HCC), as evidenced by changes in histopathological architecture, increased activity of cytochrome P450, decreased activity of glutathione Stransferase (GST) as well as decreased antioxidant status, enhanced lipid peroxidation, increased liver marker enzymes. Western blot analysis showed decreased expression of cyclin D1 and Bcl-2 with activation of caspase-3 and increased expression of Bax. Immunohistochemical demonstrated the decreased expression of the PCNA and VEGF. These results indicate that brucine prevents lipid peroxidation and hepatic cell damage and also protects the antioxidant system in DENA-induced hepatocarcinogenesis.
Camel Biomedical Research Unit, College of Pharmacy and Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: saritasaraswati@gmail.com.
Sarita
S
Saraswati
Abdulqader A
AA
Alhaider
S S
SS
Agrawal
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D010634:Phenobarbital / Q000633:toxicity; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013331:Strychnine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000477:Alkylating Agents; D016588:Anticarcinogenic Agents; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D004052:Diethylnitrosamine; C083806:brucine; D053148:Caspase 3; D013331:Strychnine; D010634:Phenobarbital
Brucine; Chemoprevention; Diethylnitrosamine; Hepatocarcinogenesis; VEGF