cytochrome-c-t and boldine

Discovering the utmost effective and targeted chemotherapy for hepatocellular carcinoma is still a significant challenge. In the present study, diethylnitrosamine was used as a liver carcinogen and boldine a compound of boldo. We anticipated the hypothesis that boldine endow antiproliferative and promote apoptosis on hepatocarcinoma rats. We analyzed that boldine alters the tumor biomarkers and liver markers enzyme levels. Also, we determined boldine modulate the enzymatic and nonenzymatic antioxidant activities, as well as messenger RNA and protein expressions of Bcl2, Bax, and cleaved caspase 3 by reverse transcription polymerase chain reaction and Western blot analysis, respectively. It was also manifested by histopathology studies in liver tissues of HCC rats. Our finding suggested that boldine has antioxidant activity, and moreover, also contributes apoptotic nature by upregulating the protein expression of Bax, and cleaved caspase 3. Our data accomplishes that boldine a candidate drug has dynamic therapeutic activity and suitable for the treatment of HCC.

Topics: alpha-Fetoproteins; Animals; Antioxidants; Apoptosis; Aporphines; bcl-2-Associated X Protein; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Caspase 3; Cell Proliferation; Cytochromes c; Diethylnitrosamine; Liver; Liver Neoplasms; Male; Oxidative Stress; Peumus; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Wistar; RNA, Messenger; Weight Gain

BACKGROUND In the present study, we explored the protective effect and mechanism of action of boldine (BOL) against neural apoptosis, which is a mediator of TBI. MATERIAL AND METHODS The effect of BOL on mitochondrial and cytosol proteins of extracted from cerebral cortical tissue of mice was evaluated. The grip test was used to assess the neurological deficit and brain water content of the subjects after administration of BOL to assess its effect on SOD, GSH, and MDA activity in brain ischemic tissues. To further confirm the effect of the BOL, the histopathological analysis and morphology of neurons were studied by Nissl staining. The effect of BOL against TBI-induced neural apoptosis by immuno-histochemistry and Western blotting assay were also studied. RESULTS BOL showed significant improvement against TBI in a dose-dependent manner. In the BOL-treated group, the apoptotic index was significantly reduced, but the level of caspase-3 was greatly diminished. Additionally, the level of the Bax in mitochondria (mit) and cytosol was elevated in the TBI-treated group as compared to the sham group. Further BOL at the test dose causes significant reduction in the level of mitochondrial MDA together with increase in SOD activity as compared to the TBI alone group. CONCLUSIONS BOL showed a cerebroprotective effect against TBI by attenuating the oxidative stress and the mitochondrial apoptotic pathway. It also inhibited mitochondrial Bax translocation and cytochrome c release.

Topics: Animals; Apoptosis; Aporphines; bcl-2-Associated X Protein; Brain Injuries, Traumatic; Caspases; Cytochromes c; Cytosol; Male; Mice; Mice, Inbred ICR; Mitochondria; Neurons; Neuroprotective Agents; Oxidative Stress; Proto-Oncogene Proteins c-bcl-2