Gallic acid-coated sliver nanoparticle alters the expression of radiation-induced epithelial-mesenchymal transition in non-small lung cancer cells.

BACKGROUND: Radiotherapy is the most widely used treatment method for treating cancer with or without surgery and chemotherapy. In lung cancer, it is one of the important treatment steps in excising the tumor from the lung tissue; unfortunately, radiation can induce epithelial- mesenchymal transition (EMT), a typical physiological process in which cuboidal shaped epithelial cell loses its phenotype and acquires mesenchymal-like phenotype thus, increases the metastasis progression in the body. To prevent EMT mediated metastasis, we aimed to 1) synthesize silver nanoparticles by using Gallic acid, a potential antioxidant which acts as stabilizing and reducing agent in the form of silver nanoparticle (GA-AgNPs) 2) to analyze its effect on EMT markers during radiation-induced EMT in A549 cells. METHODS: A549 cells were irradiated with 8Gy (X-ray) and treated with GA-AgNPs at a fixed concentration under in vitro condition. GA-AgNPs were prepared and characterized for absorption, potential stability, size and morphology by UV-Visible spectrophotometer, Zeta potential and Transmission electron microscopy respectively. After irradiation, the morphology changes were observed using an inverted microscope, the gene and protein expression of EMT markers were analyzed by RT-PCR and western blotting. RESULTS/CONCLUSION: GA-AgNPs are in nano size with fair stability. The synthesized nanoparticles suppressed the EMT markers including Vimentin, N-cadherin, Snail-1 and increased E-cadherin expression which might inhibit cancer cells to acquire radio resistant metastasis potential.

Protection against X-ray radiation-induced cellular damage of human peripheral blood lymphocytes by an aminothiazole derivative of dendrodoine.

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.

Investigation of the radioprotective efficacy of hesperidin against gamma-radiation induced cellular damage in cultured human peripheral blood lymphocytes.

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.

Lycopene: An antioxidant and radioprotector against gamma-radiation-induced cellular damages in cultured human lymphocytes.

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.

Effect of ellagic acid, a natural polyphenol, on alcohol-induced prooxidant and antioxidant imbalance: a drug dose dependent study.

INTRODUCTION: Alcohol abuse, alcohol intolerance and other alcohol-related disabilities are some of the most challenging public health problems. Alcohol, by its property of generating free radicals, causes severe damage to the membrane and affects almost all organs of the human body. Ellagic acid (EA), a natural polyphenolic compound found in fruits and nuts, possess several biological properties. Our aim was to investigate, in vivo, the antioxidant potential of ellagic acid against oxidative stress induced by alcohol intoxication. METHODS: Female albino Wistar rats were used for the study. The toxicity was induced by administering 20 percent alcohol orally (7.9 g/kg body weight) for 45 days. Rats were treated with EA at three different doses (30, 60 and 90 mg/kg body weight) via intragastric intubations. The antioxidant property of EA was studied by assessing the activities of liver marker enzymes (gamma-glutamyl transferase and alkaline phosphatase), superoxide dismutase and catalase and the levels of vitamin E, vitamin C and reduced glutathione, nitric oxide (NO), protein carbonyl content (PCC), thiobarbituric acid reactive substances (TBARS) and hydroperoxides. RESULTS: Oxidative stress was effectively modulated by EA co-administration. EA significantly improved the status of antioxidants and decreased TBARS, hydroperoxides, NO, PCC and liver marker enzymes at the dose of 60 mg/kg body weight when compared with the alcohol-treated group. CONCLUSION: The study provides the antioxidant and cytoprotective properties of EA at a dose of 60 mg/kg body weight against oxidative stress induced by alcohol.

Effect of Ellagic Acid, a Plant Polyphenol, on Fibrotic Markers (MMPs and TIMPs) during Alcohol-Induced Hepatotoxicity.

ABSTRACT Alcoholic fibrosis and its end-stage cirrhosis occur when the rate of matrix synthesis exceeds matrix degradation. Hepatic fibroproliferation is associated with alterations of hepatic tissue inhibitors of matrix metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs/matrixins) expressions. The alteration of hepatic matrixins and TIMPs expression to disease stage and inflammatory activity underlines their potential diagnostic markers in chronic liver disease. Ellagic acid (EA), a natural phenolic compound found in fruits and nuts, has potent antioxidant, anti-inflammatory, and anticancerous properties. The aim of our study was to gain further insight into the effect of EA on fibrotic markers (MMPs and TIMPs) during alcohol-induced tissue injury. To elucidate the effect on the MMPs/TIMPs balance by EA, gelatin zymography, multiwell zymography, succinylated gelatin assay, and ELISA technique (for TIMPs) were carried out. Coadministration of EA with alcohol decreased the expression of MMP-2 and -9 and TIMP-2 in a dose-dependent manner. These results suggest that EA at the dosage of 60 mg/kg body weight effectively decreased the expression pattern of fibrotic markers during alcohol-induced toxicity. Hence, it can be developed as an antifibrotic compound in near future.