ABSTRACT
This study evaluated the radioprotective effect of dendrodoine analog (DA) against radiation-induced damage in the liver of mice. The study was divided into two phases; in the first phase, the effective concentration of DA was fixed by performing a survival study. In the second phase, the fixed effective concentration of DA was orally administered to mice to evaluate its radioprotective efficacy by performing various assays. The results indicated that the radiation-induced decrease in the activities of antioxidant enzymes, increase in thiobarbituric acid reactive substances (TBARS) and comet parameters were altered by pre-administration with the effective concentration of DA which restored the antioxidant status to near normal and decreased the level of the TBARS and comet parameters. The histopathological examinations further confirmed the hepatoprotective effect of DA in mice. Thus, the current study showed DA to be an effective radioprotector against radiation induced damage in the liver of mice.
Subject(s)
Indoles/pharmacology , Radiation-Protective Agents/pharmacology , Thiadiazoles/pharmacology , X-Rays , Animals , Comet Assay , Indoles/chemistry , Liver/metabolism , Liver/pathology , Liver/radiation effects , Male , Mice , Thiadiazoles/chemistry , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
The present study was aimed to evaluate the radioprotective efficacy of dendrodoine analog (DA), an aminothiazole derivative against X-ray radiation-induced cellular damage in cultured human peripheral blood lymphocytes. Different concentrations of DA (2, 4, 6, 8, 10 microg/ml or 6.15, 12.29, 18.44, 24.59, 30.73 microM) were pre-incubated with lymphocytes for 30 min prior to irradiation [4 Gy] and the micronuclei (MN) scoring and comet assay were performed to fix the effective concentration of DA against 4 Gy irradiation-induced cellular damage. The results indicated that among all the concentrations, 6 microg/ml concentration of DA showed optimum protection by effectively decreasing the MN frequencies and comet attributes. Based on the above results, 6 microg/ml concentration of DA was fixed as the effective dose to further investigate its radioprotective efficacy. This was carried out by pre-incubating the lymphocytes with 6 microg/ml concentration of DA followed by exposure of the lymphocytes to different doses (1, 2, 3 and 4 Gy) of radiation and investigating the radiation-induced genetic damage (MN, comet assay, DNA fragmentation assay) and biochemical changes (changes in the level of enzymic and non-enzymic antioxidants, lipid peroxidation). The results indicated a dose-dependent increase in both genetic damage and thiobarbituric acid reactive substances (TBARS), accompanied by a significant decrease in the antioxidant status in the irradiated groups compared to DA treated groups which modulated the toxic effects through its antioxidant potential. Thus the current study shows DA to be an effective radioprotector against X-ray radiation induced in vitro cellular damage in lymphocytes.
Subject(s)
Indoles/chemistry , Indoles/pharmacology , Lymphocytes/drug effects , Lymphocytes/radiation effects , Radiation-Protective Agents/chemistry , Radiation-Protective Agents/pharmacology , Thiadiazoles/chemistry , Thiadiazoles/pharmacology , Adult , Antioxidants/metabolism , Cells, Cultured , Comet Assay , DNA Fragmentation/drug effects , DNA Fragmentation/radiation effects , Humans , Indoles/chemical synthesis , Lipid Peroxidation/drug effects , Lipid Peroxidation/radiation effects , Radiation-Protective Agents/chemical synthesis , Thiadiazoles/chemical synthesis , Thiazoles/chemical synthesis , Thiazoles/chemistry , Thiazoles/pharmacology , X-Rays , Young AdultABSTRACT
The present study was aimed to evaluate the radioprotective efficacy of hesperidin (HN), a flavonone glycoside against gamma-radiation-induced cellular damage in cultured human peripheral blood lymphocytes. Different concentrations of HN (3.27, 6.55, 9.83, 13.10, 16.38 and 19.65 microM) were pre-incubated with lymphocytes for 30 min prior to gamma-irradiation [4 Gy] and the micronuclei (MN) scoring, dicentric aberration and comet assay were performed to fix the effective dose of HN against gamma-irradiation induced cellular damage. The results indicated that among all the concentrations, 16.38 microM concentration of HN showed optimum protection by effectively decreasing the MN frequencies, dicentric aberrations and comet attributes. Based on the above results, 16.38 microM concentration of HN was fixed as the effective dose to further investigate its radioprotective efficacy which was then carried out by pre-incubating lymphocytes with 16.38 microM concentration of HN, exposing the lymphocytes to different doses (1, 2, 3 and 4 Gy) of radiation and investigating radiation induced genetic damage (MN, dicentric aberration, comet assay, DNA fragmentation assay) and biochemical changes (changes in the level of enzymic and non-enzymic antioxidants, lipid peroxidation). The results indicated a dose dependent increase in both genetic damage and thiobarbituric acid reactive substances (TBARS), accompanied by a significant decrease in the antioxidant status compared to HN treated groups which modulated the toxic effects through its antioxidant potential. Thus the current study shows HN to be an effective radioprotector against gamma-radiation induced in-vitro cellular damage in lymphocytes.
Subject(s)
DNA Damage/drug effects , DNA Fragmentation/drug effects , Gamma Rays , Hesperidin/pharmacology , Lymphocytes/drug effects , Oxidative Stress/drug effects , Radiation-Protective Agents/pharmacology , Adaptor Proteins, Signal Transducing , Carrier Proteins , Cell Separation , Cells, Cultured , Chromosome Aberrations/radiation effects , Comet Assay , DNA Fragmentation/radiation effects , Dose-Response Relationship, Radiation , Free Radical Scavengers , Humans , Leukocyte Count , Lipid Peroxidation , Lymphocytes/physiology , Lymphocytes/radiation effects , Micronucleus Tests , Radiation Dosage , Repressor ProteinsABSTRACT
The present study aimed to evaluate the radioprotective effect of lycopene, a naturally occurring dietary carotenoid on gamma-radiation-induced toxicity. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). The DNA damage was analyzed by cytokinesis blocked micronucleus assay (CBMN), dicentric aberration (DC) and translocation frequency. The gamma-radiation at different doses (1, 2 and 4Gy) resulted in a significant increase in the number of micronuclei (MN), DC, translocation frequency, TBARS and HP level, whereas the levels of GSH and antioxidant enzymes were significantly decreased when compared with normal control. The maximum damage to lymphocytes was observed at 4Gy irradiation. Lycopene pretreatment (1, 5 and 10microg/ml) significantly decreased the frequency of MN, DC and translocation when compared with gamma-radiation control. The levels of TBARS, HP were also decreased and activities of SOD, CAT and GPx were significantly increased along with GSH levels when compared with gamma-radiation control. The dose of 5microg/ml of lycopene was found to be more effective than the other two doses. Thus, our result shows that pretreatment with lycopene offers protection to normal lymphocytes against gamma-radiation-induced cellular damage.
Subject(s)
Antioxidants/pharmacology , Carotenoids/pharmacology , Gamma Rays , Lymphocytes/drug effects , Radiation-Protective Agents/pharmacology , Adult , Antioxidants/administration & dosage , Carotenoids/administration & dosage , Catalase/drug effects , Catalase/radiation effects , Cells, Cultured , Chromosome Aberrations/drug effects , Chromosome Aberrations/radiation effects , DNA Damage/drug effects , DNA Damage/radiation effects , Dose-Response Relationship, Drug , Glutathione Peroxidase/drug effects , Glutathione Peroxidase/radiation effects , Humans , Lipid Peroxidation/drug effects , Lipid Peroxidation/radiation effects , Lycopene , Lymphocytes/radiation effects , Micronuclei, Chromosome-Defective/drug effects , Micronuclei, Chromosome-Defective/radiation effects , Radiation Dosage , Radiation-Protective Agents/administration & dosage , Superoxide Dismutase/drug effects , Superoxide Dismutase/radiation effects , Thiobarbituric Acid Reactive Substances/metabolism , Young AdultABSTRACT
The present work was carried out to evaluate the antioxidant activity of hesperidin and to study its protective effect on H(2)O(2) induced oxidative damage on pBR322 DNA and RBC cellular membrane. The in vitro assays were performed with different concentrations (2, 4, 6, 8, and 10 microg/ml, which were equivalent to 3.27, 6.55, 9.83, 13.10, and 16.38 microM) of hesperidin and the results clearly indicate that hesperidin at 10 microg/ml exhibited radical scavenging activity greater than that of standards like ascorbic acid and trolox. The protective effect of hesperidin on pBR322 DNA and RBC cellular membrane on treatment with different concentrations of H(2)O(2) shows that hesperidin at 2.5 mM converts the open circular form (oc) of pBR322 DNA that is an indication of damage to super coiled (ccc) form and at 10 microg/ml it prevents membrane damage. Thus, our result proves hesperidin to be a valuable antioxidant that protects pBR322 DNA and RBC cellular membrane from free radical induced oxidative damage.
Subject(s)
Antioxidants/pharmacology , DNA/drug effects , Erythrocyte Membrane/drug effects , Hesperidin/pharmacology , Hydrogen Peroxide/pharmacology , Oxidants/pharmacology , Oxidative Stress/drug effects , Antioxidants/chemistry , DNA/chemistry , DNA Damage , Erythrocyte Membrane/metabolism , Free Radicals/metabolism , Hesperidin/chemistry , Humans , Lipid Peroxidation , Molecular Structure , Reactive Oxygen Species/metabolismABSTRACT
The present work was carried out to evaluate the antioxidant and free radical scavenging activity of aminothiazole derivative by performing various in vitro assays; to study its protective effect on H(2)O(2)-induced oxidative damage on pBR322 DNA and on RBC cellular membrane. The in vitro assays were performed with different concentrations of aminothiazole derivative (6.15, 12.29, 18.44, 24.59, and 30.73 microM) and the results were compared with standards like ascorbic acid and trolox. Our results clearly indicated that aminothiazole derivative at a dose of 18.44 microM exhibited radical scavenging activity greater than that of ascorbic acid and trolox. The DNA protective effect on pBR322 DNA showed that there was a concentration-dependent inhibition of the disappearance of supercoiled (ccc) form of DNA on incubation with 30 mM H(2)O(2) in the presence of different concentrations of aminothiazole derivative. Thus our compound at 1.5 mM prevents the conversion from supercoiled (ccc) form to open circular form (oc) form of pBR322 DNA. Pretreatment with aminothiazole derivative at a dose of 18.44 microM prevents membrane damage and exhibits an IC(50) value, which is the concentration of the sample required to inhibit 50% of the radical formed greater than that of the standards (ascorbic acid and trolox). Thus our compound of interest aminothiazole derivative exhibits antioxidant and free radical scavenging properties greater than that of standards like ascorbic acid and trolox and thereby protects pBR322 DNA and RBC cellular membrane from free radical induced oxidative damage.
