Selective Toxicity of Apigenin on Cancerous Hepatocytes by Directly Targeting their Mitochondria.

BACKGROUND: hepatocellular carcinoma (HCC) is the third cause of mortality due to cancer throughout the world. OBJECTIVE: The main goal of the current research was to evaluate the selective toxicity of apigenin (APG) on hepatocytes and mitochondria obtained from the liver of HCC rats). METHOD: In this research, HCC induced by a single dose of diethylnitrosamine (DEN); 200 mg/kg, i.p, and 2-acetylaminofluorene (2-AAF) (0.02%, through dietary) for 14 days. For confirmation of HCC, histopathological evaluations and determination of serum concentrations of liver toxicity enzymes and specific liver cancer marker; alpha-fetoprotein (AFP) were performed. Then, cancerous and non- cancerous hepatocytes were isolated by using the collagen perfusion method. Eventually, mitochondria isolated from HCC and normal hepatocytes were tested for every eventual toxic effects of APG. RESULTS: After confirmation of HCC, the results of this research showed that APG (10, 20 and 40 µM) increased mitochondrial parameters such as, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) level, mitochondrial swelling and cytochrome c expulsion only in cancerous hepatocytes. Apoptotic effect of APG on HCC cells was confirmed by caspase-3 activation and Annexin V-FITC and PI double staining analysis. CONCLUSION: These results propose the eligibility of the flavonoid APG as a complementary therapeutic agent for patients with hepatocellular carcinoma.

Budget impact analysis of conversion from cyclosporine to sirolimus as immunosuppressive medication in renal transplantation therapy.

OBJECTIVES: The aim of this study was to determine budget impact of conversion from cyclosporine (CsA) to sirolimus (SRL) in renal transplant therapy (RTT) from the perspective of insurance organizations in Iran. METHODS: An Excel-based model was developed to determine cost of RTT, comparing current CsA based therapy to an mTOR inhibitor-based therapy regimen. Total cost included both cost of immunosuppressive agents and relative adverse events. The inputs were derived from database of Ministry of Health and insurance organizations, hospital and pharmacy based registries, and available literature that were varied through a one-way sensitivity analysis. According to the model, there were almost 17,000 patients receiving RTT in Iran, out of which about 2,200 patients underwent the operation within the study year. The model was constructed based on the results of a local RCT, in which test and control groups received CsA, SRL, and steroids over the first 3 months posttransplantation and, from the fourth month on, CsA, mycophenolate mofetil (MMF), and steroids were used in the CsA group and SRL, MMF, and steroids were administered in the SRL group, respectively. RESULTS: The estimated cost of RTT with CsA was US$4,850,000 versus US$4,300,000 receiving SRL. These costs corresponded to the cost saving of almost US$550,000 for the payers. CONCLUSION: To evaluate the financial consequence of adding mTOR inhibitors to the insurers' formulary, in the present study, a budget impact analysis was conducted on sirolimus. Fewer cases of costly adverse events along with lower required doses of MMF related to SRL based therapies were major reasons for this saving budgetary impact.

Acute and subchronic oral toxicity of Galega officinalis in rats.

Galega officinalis L. (Papilionaceae) is widely used in folk medicine as antidiabetic or for increasing lactation. There is a little information about its possible toxicity. In this study, acute and subchronic toxicity of aerial parts of Galega officinalis in Wistar rats have been evaluated. For the acute toxicity study, the animals received orally four different single dose of plant suspension and were kept under observation for 14 days. The results indicated that LD50 of Galega officinalis is higher than 5 g/kg. In the subchronic study, 48 rats were divided into four groups and were fed a diet containing 0%, 0.15%, 1.5% and 3% (w/w) of Galega officinalis. After 90 days blood and tissue samples were taken for hematological, biochemical and histopathological determinations. An increase in serum levels of cholesterol, creatine phosphokinase, lactate dehydrogenase and total and conjugated bilirubin was observed. Some parameters such as calcium, albumin, albumin/globulin ratio, hematocrit, WBC and platelet counts were decreased. In microscopic examination, sinusoidal congestion in liver and alveolar hemorrhage was observed. Other parameters showed non-significant difference between treatment and control groups. Present data suggest that liver and lung could serve as target organs in oral toxicity of this plant.