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In this study modulatory effect of Hoechst 33258 on radiation induced membrane related signaling events which ultimately leads to apoptosis has been investigated. Splenocytes from swiss albino mice were irradiated in air at room temperature in a gamma chamber (240 TBq 60Co Model 4000 A) at the dose-rate of 0.052 Gys-1. Membrane lipid peroxidation, fluidity, specific activities of antioxidant enzymes, levels of nitric oxide, glutathione and apoptosis in presence and absence of different concentrations of Hoechst 33258 has been assayed. DNA binding activity of nuclear factor kappa B and activator protein–1 was also assayed by electrophoretic mobility shift assay. Modulatory effect of Hoechst 33258 was examined at 3 and 5 Gy using different concentrations (10, 20 and 30 µM). Hoechst 33258 was found to inhibit radiation induced peroxidative damage and fluidity and lowered the level of nitric oxide and apoptosis - as evident by DNA ladder assay and FACS, indicating free radicals scavenging potential. Dot plot diagramme clearly showed that 30 µM Hoechst 33258 caused 14% and 19% decrease in apoptotic cells at 3 Gy and 5 Gy of radiation respectively (compared to irradiated control group). Further DNA binding activity of nuclear factor kappa B and activator protein–1 was also inhibited but the antioxidant potential of the cells was enhanced. These findings support that Hoechst 33258 protects the cell from undergoing apoptosis. Hoechst 33258 may have interacted and has an ability to protect splenocytes against radiation induced apoptosis through modulation of membrane-related signaling events and antioxidant status.
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Effect of consumption of three different doses (2%, 4% and 6%, w/w) of Dolichos biflorus Linn. seeds on hepatic drug metabolizing enzymes, antioxidant enzymes, reduced glutathione content, lactate dehydrogenase and lipid peroxidation in Swiss albino mice has been reported. Anti-carcinogenic effect has been studied by 7,12-dimethylbenzanthracene (DMBA)-induced skin and benzo(a)pyrene[B(a)P]-induced forestomach papillomagenesis models. D. biflorus consumption resulted in a significant increase in hepatic carcinogen metabolizing enzyme systems especially at 4% and 6% doses. Significant increase in reduced glutathione content (GSH) and specific activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) in liver of mice, at 4% and 6% doses has been reported. Lactate dehydrogensae (LDH) activity and peroxidative damage has been significantly decreased at 4% and 6% doses. In skin papillomagenesis model, 4% and 6% dose in diet significantly reduced the tumor incidence (up to 25%), tumor multiplicity (up to 59%) and tumor volume per mouse (up to 70%) as compared to DMBA treated group. Importantly, significant reduction in tumor incidence (up to 33%) and tumor multiplicity (up to 61%) was evident for forestomach papillomagenesis model.
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Objective To observe therapeutic effects of HuGanJieXian decoction on rats hepatic fibrosis induced by tetrachloride. Methods Rat models of hepatic fibrosis were constructed by intraperitoneal injection of tetrachloride.HuGanJieXian decoction composed of low, middle, and high dose curcumin were given to these rats respectively at the same time. Sho-saiko-to compound treatment group and Fufangbiejiarangan Tablets treatment group were made as positive control groups. After twelve weeks, all rats were executed. Serum samples were kept for measuring serum levels of PC-Ⅲ, LN, and HA. Left livers were extirpated for pathologic examination including H.E and Masson stainings. Grade of hepatic fibrosis were evaluated according to SSS system. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) of supematant centrifugated from hepatic tissue homogenate were detected. Results Serum levels of PC-Ⅲ, LN, and HA were depressed obviously in decoction groups compared with those of fibrotic group (P<0.05) , especially in the low-dose curcumin group.HuGanJieXian Decoction could increase the level of SOD and decrease the level of MDA (P<0.05) , especially in the low-dose curcumin group. Staining of H. E and Masson showed that degrees of hepatic fibrosis in decoction groups were improved obviously compared with that of the fibrotic group. Conclusion HuGanJieXian Decoction can improve rat hepatic fibrosis, the mechanism of this effect may be associated with protecting hepatic cell membrane and anti- peroxidative damage.
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Objective To observe the antioxidative capability and the mRNA expression of sodium pump αl-subunit in kidney of hypothyroid rats by iodine deficiency and illuminate the pathogenesis of kidney damage.Methods Wistar rats were randomly divided into two groups as control group (NT) and hypothyroid group (HT).The rats were all fed with low-iodine diet derived from an endemic goiter area and drank deionized water containing different potassium iodide to duplicate hypothyriod animal models.We determined the morphometric parameters of kidney by routine histology method.The contents of malondialdehyde and free radical scavengers (GSH-PX and SOD) in kid-ney,as well as the activity of Na~+-K~+ ATPase were measured in two groups.The mRNA expression of sodium pump α1 subunit was determined by reverse transcription-polymerase chain reaction.Results Compared with that in the control group,in hypothyroid group (1) serum free T3,free T4,total T3 and total T4 were markedly lower.(2) mean glomerular area and volum diminished markedly.(3)the content of MDA and activity of PGx increased markedly,but the activity of SOD decreased significantly,as well as the one of Na~+-K~+-ATPase.(4)the mRNA expression level of sodium pump α1 subunit was lower.Conclusion In a hypothyroid state,the decrease of antiox-idative capability of kidney resulted in lipid peroxidative damage,atrophy of kidney,decreased activity of Na~+-K~+ -ATPase and degression of sodium pump α1 subunit mRNA expression.
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The antioxidative capability and Na+-K+-ATPase α1-subunit mRNA expression in myocardium of hypothyroid rats induced by low-iodine diet were observed. The results showed that the antioxidative capability of myocardium decreased, resulting in lipid peroxidative damage, atrophy of myocardial cells and chondrification of tunica intima, along with decreased expression of sodium pump α1 subunit mRNA in hypothyroid rats.
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Aim To study the influence of Liensinine(LIE) on the oxidative damage of erythrocyte ghost. Method The erythrocyte ghost oxidative injury caused by super oxide anion (O?_2) from the auto-oxidation of pyrogallic acid was used as model. The effect of LIE on oxidated erythrocyte ghost was observed by the measurement of the malonidial aldehyde (MDA)-the degradation product of lipid peroxidation, blocking degree, speed of auto-oxidation and membrane fluidity. Result O?_2 caused lipid peroxidation of erythrocyte ghost, increased the content of MDA and the speed of auto-oxidation, decreased membrane fluidity, and alleviated blocking degree. But LIE(80, 100, 120 mg?L -1 )could decrease the content of MDA and speed of auto-oxidation markedly, improve the membrane fluidity and blocking degree significantly, and inhibit the lipid peroxidation. Conclusion LIE has protective action on the oxidative damage of erythrocyte ghost initiated by O?_2