ABSTRACT
Objective: To investigate the hepatorenoprotective effects of Origanum vulgare L. against finasteride-induced oxidative injury in the liver and kidney of mice. Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS) analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents. Thirty BALB/c mice received 0.5 mL/day distilled water, finasteride (25 mg/kg/day for 10 d), and 100, 200, or 400 mg/kg/day finasteride + Origanum vulgare extract with 6 mice per group for five weeks. On day 36, liver and kidney function as well as pro-and antiinflammatory (IFN-γ, IL-12, IL-6, TNF-α, IL-1β, and IL-10) cytokines were measured. The total antioxidant status, nitric oxide (NO), and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated. Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities. Results: Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS. Origanum vulgare extract, especially at 200 and 400 mg/kg/day doses, significantly improved liver and kidney biochemical indices, decreased inflammatory cytokines, increased total antioxidant status and NO synthase and catalase activities, as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group. Histopathological results further confirmed the protective effect of Origanum vulgare extract. Conclusions: Origanum vulgare extract ameliorates finasteride-induced hepatic and renal biochemical and histopathological alterations, and restores antioxidant/oxidant balance.
ABSTRACT
Objective: To investigate the hepatorenoprotective effects of Origanum vulgare L. against finasteride-induced oxidative injury in the liver and kidney of mice. Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS) analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents. Thirty BALB/c mice received 0.5 mL/day distilled water, finasteride (25 mg/kg/day for 10 d), and 100, 200, or 400 mg/kg/day finasteride + Origanum vulgare extract with 6 mice per group for five weeks. On day 36, liver and kidney function as well as pro-and antiinflammatory (IFN-γ, IL-12, IL-6, TNF-α, IL-1β, and IL-10) cytokines were measured. The total antioxidant status, nitric oxide (NO), and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated. Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities. Results: Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS. Origanum vulgare extract, especially at 200 and 400 mg/kg/day doses, significantly improved liver and kidney biochemical indices, decreased inflammatory cytokines, increased total antioxidant status and NO synthase and catalase activities, as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group. Histopathological results further confirmed the protective effect of Origanum vulgare extract. Conclusions: Origanum vulgare extract ameliorates finasteride-induced hepatic and renal biochemical and histopathological alterations, and restores antioxidant/oxidant balance.
ABSTRACT
Objective: To investigate the hepatorenoprotective effects of Origanum vulgare L. against finasteride-induced oxidative injury in the liver and kidney of mice. Methods: Liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI/MS) analysis was utilized to yield a fingerprint of Origanum vulgare polyphenolic constituents. Thirty BALB/c mice received 0.5 mL/day distilled water, finasteride (25 mg/kg/day for 10 d), and 100, 200, or 400 mg/kg/day finasteride + Origanum vulgare extract with 6 mice per group for five weeks. On day 36, liver and kidney function as well as pro- and anti-inflammatory (IFN-γ, IL-12, IL-6, TNF-α, IL-1β, and IL-10) cytokines were measured. The total antioxidant status, nitric oxide (NO), and malondialdehyde levels as well as the activities of NO synthase and catalase were also evaluated. Histopathological study was conducted to assess the effect of Origanum vulgare extract on finasteride-induced renal and hepatic toxicities. Results: Twenty-five major polyphenolic compounds were identified in the Origanum vulgare extract by LC-ESI/MS. Origanum vulgare extract, especially at 200 and 400 mg/kg/day doses, significantly improved liver and kidney biochemical indices, decreased inflammatory cytokines, increased total antioxidant status and NO synthase and catalase activities, as well as decreased plasma NO and malondialdehyde levels in a dose-dependent manner as compared to the finasteride group. Histopathological results further confirmed the protective effect of Origanum vulgare extract. Conclusions: Origanum vulgare extract ameliorates finasteride-induced hepatic and renal biochemical and histopathological alterations, and restores antioxidant/oxidant balance.
ABSTRACT
<p><b>OBJECTIVE</b>To study the inhibitory effects of antisense bicistronic recombinant adenovirus vector of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (Ad-ODC-AdoMetDCas) on polyamine biosynthesis,proliferation and invasion of lung cancer cells.</p><p><b>METHODS</b>Adenovirus-mediated gene transduction efficiency was assessed with counting GFP-positive cells using trypan blue. Western Blot and HPLC were used to detect ODC and S-AdoMetDC expression and polyamine content in A-549 cells respectively. Viable cell counting and cell cycle analysis were adopted to evaluate cell growth and cell cycle distribution, and A-549 cell invasion in vitro was detected with Matrigel invasion assay.</p><p><b>RESULTS</b>Approximate 75% of A-549 cells were infected with Ad-ODC-AdoMetDCas when multiplicity of infection reached 50. Our study demonstrated that Ad-ODC-AdoMetDCas vector-mediated gene transfer inhibited tumor cell growth through the blockade of polyamine synthesis pathway. The tumor cells were arrested at cell cycle G1 phase after gene transfer. Gene transferred tumor cells were shown to possess markedly decreased invasiveness.</p><p><b>CONCLUSION</b>Ad-ODC-AdoMetDCas has significant inhibitory effects on lung cancer cell proliferation and invasion and bears therapeutic potential for the treatment of lung cancer.</p>