Myricetin Selectively Induces Apoptosis on Cancerous Hepatocytes by Directly Targeting Their Mitochondria.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. In patients for whom HCC could not be detected early, current treatments show poor tolerance and low efficacy. So, alternative therapies with good efficacy are urgently needed. The aim of this research was to evaluate the selective apoptotic effects of myricetin (MYR), a flavonoid compound, on hepatocytes and mitochondria obtained from the liver of HCC rats. In this study, HCC induced by diethylnitrosamine (DEN), as an initiator, and 2-acetylaminofluorene (2-AAF), as a promoter. To confirm the HCC induction, serum levels of alpha-fetoprotein (AFP), AST, AST and ALP and histopathological changes in the liver tissue were evaluated. Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effects of MYR were isolated, and mitochondrial and cellular parameters related to apoptosis signalling were then determined. Our results showed that MYR was able to induce cytotoxicity only in hepatocytes from the HCC but not from the untreated control group. Besides, MYR (12.5, 25 and 50 µM) induced a considerable increase in reactive oxygen species (ROS) level, mitochondrial swelling, mitochondrial membrane permeabilization (MMP) and cytochrome c release only in cancerous but not in untreated normal hepatocyte mitochondria. MYR selectively increased caspase-3 activation and apoptotic phenotypes in HCC, but not untreated normal hepatocytes. Finally, our finding underlines MYR as a promising therapeutic candidate against HCC and recommends the compound for further studies.

Safety assessment of ocimum basilicum hydroalcoholic extract in wistar rats: acute and subchronic toxicity studies.

OBJECTIVES: Ocimum basilicum L. is widely used in folk medicine of many countries including . Both O. basilicum and its oil extract have received considerable attention for their potential medicinal properties, but there are a few reports about possible toxicity of this plant. Therefore, in the present study, acute and subchronic toxicity of O. basilicum hydroalcohlic extract have been evaluated in Wistar rats. MATERIALS AND METHODS: For the acute toxicity assessment, five groups of 10 animals (5 male, 5 female) received four different single dose of extract orally, the animals were, then, kept under observation for 14 days. For subchronic toxicity, the animals were divided into four groups (5 male, 5 female) and were gavaged daily by 50, 200 and 500 mg/kg of extract. Mortality, clinical signs, body weight changes, food and water consumption, and hematological and biochemical parameters were monitored during the study period. On the 45th day, animals were sacrificed and gross findings, weight of liver and left kidney and liver histological markers were assessed. RESULTS: The results of acute study indicated that LD50 of O. basilicum is higher than 5 mg/kg. In subchronic study, no adverse effects were observed on serum parameters in male and female rats. The hematological results showed a reduction in the hematocrit, platelets and RBC in both sexes. No abnormalities were observed in other parameters. CONCLUSION: Based on the results of this study, present data suggest that hematologic system could serve as a target organ in oral toxicity of this plant.