ABSTRACT
This study aims to investigate whether asiaticoside, a triterpene glycoside, can afford protection to DNA from alterations induced by gamma radiation under in vitro, ex vivo, and in vivo conditions. In vitro studies were done on plasmid pBR322 DNA, ex vivo studies were done on cellular DNA of human peripheral blood leukocytes, and in vivo investigations were conducted on cellular DNA of spleen and bone marrow cells of mice exposed to whole-body gamma radiation. The supercoiled form of the plasmid pBR322 DNA upon exposure to the radiation was converted into relaxed open circular form due to induction of strand breaks. Presence of asiaticoside along with the DNA during irradiation prevented the relaxation of the supercoiled form to the open circular form. When human peripheral blood leukocytes were exposed to gamma radiation, the cellular DNA suffered strand breaks as evidenced by the increased comet parameters in an alkaline comet assay. Asiaticoside, when present along with blood during irradiation ex vivo, prevented the strand breaks and the comet parameters were closer to that of the controls. Whole-body exposure of mice to gamma radiation resulted in a significant increase in comet parameters of DNA of bone marrow and spleen cells of mice as a result of radiation-induced strand breaks in DNA. Administration of asiaticoside prior to whole-body radiation exposure of the mice prevented this increase in radiation-induced increase in comet parameters, which could be the result of protection to DNA under in vivo conditions of radiation exposure. Thus, it can be concluded from the results that asiaticoside can offer protection to DNA from radiation-induced alterations under in vitro, ex vivo, and in vivo conditions.
Subject(s)
DNA Damage/drug effects , Gamma Rays/adverse effects , Leukocytes, Mononuclear/drug effects , Radiation Injuries, Experimental/prevention & control , Radiation-Protective Agents/pharmacology , Triterpenes/pharmacology , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/radiation effects , Cell Line , Comet Assay , DNA Damage/radiation effects , Dose-Response Relationship, Radiation , Humans , Leukocytes, Mononuclear/pathology , Leukocytes, Mononuclear/radiation effects , Male , Mice , Molecular Structure , Plasmids/drug effects , Plasmids/radiation effects , Radiation Injuries, Experimental/genetics , Radiation-Protective Agents/chemistry , Radiation-Protective Agents/therapeutic use , Spleen/cytology , Spleen/drug effects , Spleen/radiation effects , Triterpenes/chemistry , Triterpenes/therapeutic use , Whole-Body IrradiationABSTRACT
Water dispersible Fe3O4 nanoparticles (coated with Poly Vinyl Pyrolidone (PVP) and Poly oxy ethylene 25-propylene glycol stearate (POES)) and complexed with Doxorubicin has been prepared and characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). The antitumor activity of these particles has been studied by targeting the complex to the tumor site, using an externally applied magnetic field, after oral administration of the magnetic nanoparticle-drug complexes. Our results reveal that the chemotherapy effect of Doxorubicin could be considerably enhanced by combination of the application of the drug-conjugated magnetic Fe3O4 nanoparticles, which are biocompatible and stable, and targeted drug delivery with a magnet. The present report provides the first evidence for the promising application of this novel approach with PVP coated Fe3O4 nanoparticles for cancer therapy using an in vivo murine model.
Subject(s)
Doxorubicin/administration & dosage , Doxorubicin/chemistry , Drug Carriers/chemistry , Ferric Compounds/chemistry , Lymphoma/drug therapy , Nanoparticles/chemistry , Water/chemistry , Administration, Oral , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Cell Line, Tumor , Diffusion , Drug Carriers/radiation effects , Electromagnetic Fields , Ferric Compounds/radiation effects , Lymphoma/pathology , Mice , Nanoparticles/radiation effects , Nanoparticles/ultrastructure , Particle Size , Treatment OutcomeABSTRACT
Alpha-tocopherol monoglucoside (TMG), a water-soluble derivative of alpha-tocopherol, has been examined for its ability to protect DNA against radiation-induced strand breaks. Gamma radiation, up to a dose of 6 Gy (dose rate, 0.7 Gy/minute), induced a dose-dependent increase in single strand breaks (SSBs) in plasmid pBR322 DNA. TMG inhibited the formation of gamma-radiation induced DNA single strand breaks (SSBs) in a concentration-dependent manner; 500 microM of TMG protected the single strand breaks completely. It also protected thymine glycol formation induced by gamma-radiation in a dose-dependent manner, based on an estimation of thymine glycol by HPLC.
