AIMS: This study was performed to evaluate the therapeutic efficacy of nanocapsulated flavonoidal quercetin (QC) in combating arsenic-induced reactive oxygen species (ROS)-mediated oxidative damage in hepatocytes and brain cells in a rat model. MAIN METHODS: Hepatic and neuronal cell damage in rats was made by a single injection (sc) of sodium arsenite (NaAsO(2), 13 mg/kg b. wt. in 0.5 ml of physiological saline). A single dose of 500 microl of quercetin suspension (QC) (QC 8.98 micromol/kg) or 500 microl of nanocapsulated QC (NPQC) (QC 8.98 micromol/kg) was given orally to rats at 90 min prior to the arsenite injection. KEY FINDINGS: Inorganic arsenic depositions (182+/-15.6 and 110+/-12.8 ng/g protein) were found in hepatic and neuronal mitochondrial membranes. Antioxidant levels in hepatic and neuronal cells were reduced significantly by arsenic. NPQC prevented the arsenite-induced reduction in antioxidant levels in the liver and brain. Arsenic induced a substantial decrease in liver and brain cell membrane microviscosities, and NPQC treatment resulted in a unique protection against the loss. A significant correlation between mitochondrial arsenic and its conjugated diene level was observed both in liver and brain cells for all experimental rats. SIGNIFICANCE: Arsenic-specific antidotes are used against arsenic-induced toxicity. However, the target site is poorly recognized and therefore achieving an active concentration of drug molecules can be a challenge. Thus, our objective was to formulate NPQC and to investigate its therapeutic potential in an oral route against arsenite-induced hepatic and neuronal cell damage in a rat model.
AIMS: This study was performed to evaluate the therapeutic efficacy of nanocapsulated flavonoidalquercetin (QC) in combating arsenic-induced reactive oxygen species (ROS)-mediated oxidative damage in hepatocytes and brain cells in a rat model. MAIN METHODS:Hepatic and neuronal cell damage in rats was made by a single injection (sc) of sodium arsenite (NaAsO(2), 13 mg/kg b. wt. in 0.5 ml of physiological saline). A single dose of 500 microl of quercetin suspension (QC) (QC 8.98 micromol/kg) or 500 microl of nanocapsulated QC (NPQC) (QC 8.98 micromol/kg) was given orally to rats at 90 min prior to the arsenite injection. KEY FINDINGS:Inorganicarsenic depositions (182+/-15.6 and 110+/-12.8 ng/g protein) were found in hepatic and neuronal mitochondrial membranes. Antioxidant levels in hepatic and neuronal cells were reduced significantly by arsenic. NPQC prevented the arsenite-induced reduction in antioxidant levels in the liver and brain. Arsenic induced a substantial decrease in liver and brain cell membrane microviscosities, and NPQC treatment resulted in a unique protection against the loss. A significant correlation between mitochondrial arsenic and its conjugated diene level was observed both in liver and brain cells for all experimental rats. SIGNIFICANCE: Arsenic-specific antidotes are used against arsenic-induced toxicity. However, the target site is poorly recognized and therefore achieving an active concentration of drug molecules can be a challenge. Thus, our objective was to formulate NPQC and to investigate its therapeutic potential in an oral route against arsenite-induced hepatic and neuronal cell damage in a rat model.
Authors: Andreas M Grabrucker; Barbara Ruozi; Daniela Belletti; Francesca Pederzoli; Flavio Forni; Maria Angela Vandelli; Giovanni Tosi Journal: Tissue Barriers Date: 2016-02-25
Authors: Lara Gibellini; Marcello Pinti; Milena Nasi; Jonas P Montagna; Sara De Biasi; Erika Roat; Linda Bertoncelli; Edwin L Cooper; Andrea Cossarizza Journal: Evid Based Complement Alternat Med Date: 2011-04-14 Impact factor: 2.629