5 research outputs found
Segmental aging underlies the development of a Parkinson phenotype in the AS/AGU rat
There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4a expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson's disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging
Cinnamon oil nanoemulsion as a novel nanocarrier for bleomycin amplifies its apoptotic effect on SKOV-3 ovarian cancer cells
697-704Loading the chemotherapeutic agents in nanoemulsions system has recently gained attraction in medicine due to their ability to improve the drug’s efficacy and reduce its adverse effects. In this context, here, we loaded bleomycin (BLM) in nanoemulsion (NE) consisting of cinnamon oil in order to evaluate its antineoplastic effect on the SKOV-3 cells. The produced NE formulas were physically characterized by the zetasizer. The cytotoxic activities of BLM and NE formulas were examined by CCK-8 kit, Coomassie blue staining for the visualization of the morphological changes, Annexin V-FITC for identifying apoptosis and cell death detection ELISA plus kit for DNA fragmentation measurement. The average droplet diameter of the blank NE (450.90±1.57 nm) was increased when loaded with BLM (522.57±0.85 nm) while the magnitude of the negative zeta potential of the loaded formula (0.381±0.003 mV) was less than the blank NE (1.01±0.020 mV). The potential cytotoxicity of the BLM-NE was significantly greater than the toxicities of the free BLM and blank NE. The blank NE and BLM-NE have the greatest apoptotic effect and higher enrichment factor compared to free BLM. Loading BLM in NE based on cinnamon oil has considerably improved its efficacy as an anticancer drug on the SKOV-3 cells
Cinnamon oil nanoemulsion as a novel nanocarrier for bleomycin amplifies its apoptotic effect on SKOV-3 ovarian cancer cells
Loading the chemotherapeutic agents in nanoemulsions system has recently gained attraction in medicine due to their ability to improve the drug’s efficacy and reduce its adverse effects. In this context, here, we loaded bleomycin (BLM) in nanoemulsion (NE) consisting of cinnamon oil in order to evaluate its antineoplastic effect on the SKOV-3 cells. The produced NE formulas were physically characterized by the zetasizer. The cytotoxic activities of BLM and NE formulas were examined by CCK-8 kit, Coomassie blue staining for the visualization of the morphological changes, Annexin V-FITC for identifying apoptosis and cell death detection ELISA plus kit for DNA fragmentation measurement. The average droplet diameter of the blank NE (450.90±1.57 nm) was increased when loaded with BLM (522.57±0.85 nm) while the magnitude of the negative zeta potential of the loaded formula (0.381±0.003 mV) was less than the blank NE (1.01±0.020 mV). The potential cytotoxicity of the BLM-NE was significantly greater than the toxicities of the free BLM and blank NE. The blank NE and BLM-NE have the greatest apoptotic effect and higher enrichment factor compared to free BLM. Loading BLM in NE based on cinnamon oil has considerably improved its efficacy as an anticancer drug on the SKOV-3 cells
A biochemical, theoretical and immunohistochemical study comparing the therapeutic efficacy of curcumin and taurine on T-2 toxin induced hepatotoxicity in rats
Introduction: Foodborne trichothecene T-2 Toxin, is a highly toxic metabolite produced by Fusarium species contaminating animal and human food, causing multiple organ failure and health hazards. T-2 toxins induce hepatotoxicity via oxidative stress causing hepatocytes cytotoxicity and genotoxicity. In this study, curcumin and taurine were investigated and compared as antioxidants against T-2-provoked hepatotoxicity.Methods: Wistar rats were administrated T-2 toxin sublethal oral dose (0.1 mg/kg) for 2 months, followed by curcumin (80 mg/kg) and taurine (50 mg/kg) for 3 weeks. Biochemical assessment of liver enzymes, lipid profiles, thiobarbituric acid reactive substances (TBARs), AFU, TNF-α, total glutathione, molecular docking, histological and immunohistochemical markers for anti-transforming growth factor-β1 (TGFβ1), double-strand DNA damage (H2AX), regeneration (KI67) and apoptosis (Active caspase3) were done.Results and Discussion: Compared to T-2 toxin, curcumin and taurine treatment significantly ameliorated hepatoxicity as; hemoglobin, hematocrit and glutathione, hepatic glycogen, and KI-67 immune-reactive hepatocytes were significantly increased. Although, liver enzymes, inflammation, fibrosis, TGFβ1 immunoexpressing and H2AX and active caspase 3 positive hepatocytes were significantly decreased. Noteworthy, curcumin’s therapeutic effect was superior to taurine by histomorphometry parameters. Furthermore, molecular docking of the structural influence of curcumin and taurine on the DNA sequence showed curcumin’s higher binding affinity than taurine.Conclusion: Both curcumin and taurine ameliorated T-2 induced hepatotoxicity as strong antioxidative agents with more effectiveness for curcumin