scholarly journals In Vivo Radioprotective Activity of Cell-Permeable Bifunctional Antioxidant Enzyme GST-TAT-SOD against Whole-Body Ionizing Irradiation in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jianru Pan ◽  
Huocong He ◽  
Ying Su ◽  
Guangjin Zheng ◽  
Junxin Wu ◽  
...  

GST-TAT-SOD was the fusion of superoxide dismutase (SOD), cell-permeable peptide TAT, and glutathione-S-transferase (GST). It was proved to be a potential selective radioprotector in vitro in our previous work. This study evaluated the in vivo radioprotective activity of GST-TAT-SOD against whole-body irradiation. We demonstrated that intraperitoneal injection of 0.5 ml GST-TAT-SOD (2 kU/ml) 2 h before the 6 Gy whole-body irradiation in mice almost completely prevented the splenic damage. It could significantly enhance the splenic antioxidant activity which kept the number of splenic white pulp and consequently resisted the shrinkage of the spleen. Moreover, the thymus index, hepatic antioxidant activity, and white blood cell (WBC) count of peripheral blood in irradiated mice pretreated with GST-TAT-SOD also remarkably increased. Although the treated and untreated irradiated mice showed no significant difference in the growth rate of animal body weight at 7 days postirradiation, the highest growth rate of body weight was observed in the GST-TAT-SOD-pretreated group. Furthermore, GST-TAT-SOD pretreatment increased resistance against 8 Gy whole-body irradiation and enhanced 30 d survival. The overall effect of GST-TAT-SOD seemed to be a bit more powerful than that of amifostine. In conclusion, GST-TAT-SOD would be a safe and potentially promising radioprotector.

2017 ◽  
Vol 56 (6) ◽  
pp. 703-710
Author(s):  
Michaela Lackner ◽  
Günter Rambach ◽  
Emina Jukic ◽  
Bettina Sartori ◽  
Josef Fritz ◽  
...  

Abstract No data are available on the in vivo impact of infections with in vitro azole-resistant Aspergillus fumigatus in immunocompetent hosts. Here, the aim was to investigate fungal fitness and treatment response in immunocompetent mice infected with A. fumigatus (parental strain [ps]) and isogenic mutants carrying either the mutation M220K or G54W (cyp51A). The efficacy of itraconazole (ITC) and posaconazole (PSC) was investigated in mice, intravenously challenged either with a single or a combination of ps and mutants (6 × 105 conidia/mouse). Organ fungal burden and clinical parameters were measured. In coinfection models, no fitness advantage was observed for the ps strain when compared to the mutants (M220K and G54W) independent of the presence or absence of azole-treatment. For G54W, M220K, and the ps, no statistically significant difference in ITC and PSC treatment was observed in respect to fungal kidney burden. However, clinical parameters suggest that in particular the azole-resistant strain carrying the mutation G54W caused a more severe disease than the ps strain. Mice infected with G54W showed a significant decline in body weight and lymphocyte counts, while spleen/body weight ratio and granulocyte counts were increased. In immunocompetent mice, in vitro azole-resistance did not translate into therapeutic failure by either ITC or PSC; the immune system appears to play the key role in clearing the infection.


1981 ◽  
Vol 240 (3) ◽  
pp. G225-G231
Author(s):  
R. P. Cornell

In contrast to previous studies of neutrophils from diabetic animals and humans in vitro and of macrophages from diabetic humans in vivo, which reported phagocytic depression, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon was observed in rats at 14 and 28 days after diabetes induction with streptozotocin (STZ). Carbon clearance half times were significantly enhanced to 6.3 +/- 0.79 and 8.1 +/- 1.04 min at 14 and 28 days post-STZ, respectively, compared with the nondiabetic value (12.7 +/- 0.98 min). The severity of uncontrolled STZ-induced diabetes in rats was confirmed by significant hypoinsulinemia, hyperglucagonemia, hyperglycemia, and hyperlipidemia. Although body weights of STZ-diabetic animals declined progressively, liver weights as a percent of body weight increased above the control value at 14 and 28 days post-STZ. In fact, expression of carbon phagocytosis as the corrected phagocytic index, which accounts for changes in liver and spleen weights relative to body weight, eliminated the significant difference between STZ-diabetic and nondiabetic animals. Antibiotic treatment of diabetic rats failed to alter the hyperphagocytosis, implying that a chronic bacterial infection was not the cause of phagocytic stimulation. Daily insulin replacements, but not a single large insulin dose to 14-day post-STZ rats, reversed the enhanced phagocytosis of colloidal carbon.


Author(s):  
Dian Ratih Laksmitawati ◽  
Rininta Firdaus ◽  
Mediana Astika Zein

Objectives: This study would like to investigate the in vitro antioxidant activity through 2,2-diphenyl-1-picrylhydrazyl assay and in vitro xanthine oxidase activity of the bulbs. This study performs in vivo assays to study the antihyperuricemic activity and antioxidant in the hyperuricemic rat through plasma malondialdehyde measurement. Method: The study was conducted by testing the fresh bulbs of bawang tiwai (Eleutherine palmifolia (L.) Merr. with chemical solvent of ethanol 70% to extract the bulbs. Allopurinol and Vitamin C were used as positive control for the antihyperuricemic assay and antioxidant assay, respectively. Other chemical substances were also used in this study. This study used chicken extract (Brands) 20 ml/kg/body weight to induce the level of uric acid in the blood serum, and potassium oxonate (Sigma 156124) to inhibit the uricase in rats. Results: The results show that the levels of uric acid were measured using spectrophotometer with dichloro-hydroxybenzen sulfonate (Biolabo) a as reagent. The ethanol extract of bawang tiwai (EBT) (E. palmifolia (L.) Merr) was potential to reduce uric acid level at 140, 280, and 560 mg/kg body weight, but possibly without inhibition against xanthine oxydase activity. Conclusion: All doses of EBT could inhibit lipid peroxidation in hyperuricemic condition caused by high purine diet in 14 days.


1968 ◽  
Vol 54 (5) ◽  
pp. 361-368
Author(s):  
Giorgio Cittadini ◽  
Tommaso De Cata ◽  
Carlo Gubinelli

ATPC+ ascites tumor transplants of different size were performed in NMRI mice. Hematoporphyrin chlorhydrate (Hp) was administered i.p. once daily during the seven days following transplantation. In the first series « in vivo » (1.9 x 106 cells; 0.1, 0.3, 0.9 mg of Hp), body weight, ascitogenic time (Tasc) and total ascitic volume (TV) were determined. Hematoporphyrin-treated animals showed, after the apprearance of the ascites, a body weight loss superior to controls, due to the drug toxicity caused by Hp vs. ascitic fluid interaction. Neither Tasc nor TV were significantly modified. In the second series « in vivo » (2.3 x 104 or 2.3 x 102 cells; 0.3 mg Hp), body weight loss was lower, Tasc was significantly increased and also the survival varied. In a third experiment ATPC+ cells were incubated « in vitro » with Hp in a range from 102 to 108 molecules/cell). No effect was observed on growth rate when the cells were transplanted into the host.


1992 ◽  
Vol 83 (2) ◽  
pp. 183-190 ◽  
Author(s):  
P. C. Dagnelie ◽  
D. K. Menon ◽  
I. J. Cox ◽  
J. D. Bell ◽  
J. Sargentoni ◽  
...  

1. 31P n.m.r. spectroscopy in vivo was used to study the effect of l-alanine infusion on the concentrations of gluconeogenic intermediates in normal human liver. Studies were performed in six healthy male subjects (34–44 years, fasted overnight) using a chemical shift imaging pulse sequence on a whole-body n.m.r. system operating at 1.6T. Hepatic 31P n.m.r. spectra were obtained from 10 min before to 70 min after intravenous administration of 0.70 (n = 2), 1.40 (n = 3) or 2.80 (n = 5) nmol of l-alanine/kg body weight over 4.5 min. Concentrations of phosphomonoesters, Pi and phosphodiesters relative to ATP were calculated from peak areas in the n.m.r. spectra, using the β-ATP peak as a reference. 2. Dose-dependent spectral changes were observed for [phosphomonoesters]/[ATP] and [Pi]/[ATP]. At the highest dose given, maximal changes in [phosphomonoesters]/[ATP] (mean ± sem: 98 ± 12%, P<0.005) and [Pi]/[ATP] (−33 ± 3%, P<0.001) were observed approximately 45 min after the l-alanine infusion. [Phosphodiesters]/[ATP] showed a maximal increase of 24 ± 6% (P<0.05), which was independent of the l-alanine dose. Hepatic ATP levels and pH did not change. 3. To identify the metabolites responsible for the changes observed in vivo, male Wistar rats were infused with 11.2 mmol of l-alanine/kg body weight. After 15 min, livers were freeze-clamped and were extracted according to standard procedures. In vitro, 31P n.m.r. spectra obtained at 8.4 or 11.7 T revealed sharp increases in the concentrations of 3-phosphoglycerate and phosphoenolpyruvate after l-alanine infusion. No significant increases in other metabolites contributing to the phosphomonoester or phosphodiester resonances in vivo were observed, suggesting that the rise in [phosphomonoesters] observed in vivo was caused by increasing concentrations of 3-phosphoglycerate, and that phosphoenolpyruvate contributed to the rise in [phosphodiesters]. 5. These results show that l-alanine infusion leads to consistent changes in the 31P n.m.r. spectra of the human liver owing to increased concentrations of gluconeogenic intermediates. The ‘n.m.r.-alanine test’ may constitute a useful tool for studies of gluconeogenesis and hepatic biochemical pathology in vivo.


Author(s):  
Dian Ratih Laksmitawati ◽  
Rininta Firdaus ◽  
Mediana Astika Zein

Objectives: This study would like to investigate the in vitro antioxidant activity through 2,2-diphenyl-1-picrylhydrazyl assay and in vitro xanthine oxidase activity of the bulbs. This study performs in vivo assays to study the antihyperuricemic activity and antioxidant in the hyperuricemic rat through plasma malondialdehyde measurement. Method: The study was conducted by testing the fresh bulbs of bawang tiwai (Eleutherine palmifolia (L.) Merr. with chemical solvent of ethanol 70% to extract the bulbs. Allopurinol and Vitamin C were used as positive control for the antihyperuricemic assay and antioxidant assay, respectively. Other chemical substances were also used in this study. This study used chicken extract (Brands) 20 ml/kg/body weight to induce the level of uric acid in the blood serum, and potassium oxonate (Sigma 156124) to inhibit the uricase in rats. Results: The results show that the levels of uric acid were measured using spectrophotometer with dichloro-hydroxybenzen sulfonate (Biolabo) a as reagent. The ethanol extract of bawang tiwai (EBT) (E. palmifolia (L.) Merr) was potential to reduce uric acid level at 140, 280, and 560 mg/kg body weight, but possibly without inhibition against xanthine oxydase activity. Conclusion: All doses of EBT could inhibit lipid peroxidation in hyperuricemic condition caused by high purine diet in 14 days.


2021 ◽  
Vol 12 (3) ◽  
pp. 3106-3116

The antioxidant activity of S-alkyl-4-aminobenzene-, S-allyl-4-aminobenzene- and 4-acetylaminobenzenethiosulfonates were determined by DPPH assay in experiments in vitro to establish the relationship between their structure and activity. Among the test compounds, the highest rates of these activities were found for S-allyl-4-aminobenzenethiosulfonate (ATS), S-ethyl-4-aminobenzene thiosulfonate (ETS), and S-allyl-acetyl-aminobenzenesulfonate (AATS). These compounds were studied in experiments in vivo. The processes of lipid peroxidation (LPO) and the state of the antioxidant system in the blood of rats under the influence of thiosulfonates were studied. The use of thiosulfonate additive to feed at a concentration of 100 mg/kg body weight of animals for 21 days did not cause pathological changes in rats' blood and positively influenced antioxidant blood levels.


Author(s):  
S. W. Odeyemi ◽  
J. De La Mare ◽  
A. L. Edkins ◽  
A. J. Afolayan

Abstract Background The cytotoxic properties of nanoparticles have attracted a great deal of attention in the field of nanoscience and nanotechnology due to their small size and ability to penetrate cellular membranes. Methods The silver nanoparticles were synthesized using Elaeodendron croceum stem bark and characterized. The oral acute toxicity studies were carried out by administration of 500, 1000, 2000 mg/kg body weight to Wister rats in respective groups. An in vitro cytotoxicity assay was evaluated in MDA-MB-231 breast cancer cells using the WST-1 Cell Proliferation assay. The percentage of cell viability after treatment with aqueous extracts of Elaeodendron croceum (ECE) and Elaeodendron croceum silver nanoparticles (ECAgNPs) was compared with that of paclitaxel. Results The in vivo studies revealed that the LD50 was higher than 2000 mg/kg and there was no significant difference (p>0.05) between the treatment groups compared with the control group for mean organ-to-body weight ratio except in the liver and in all hematological parameters except WBC and hematocrit. Similarly, there was no significant difference (p>0.05) for serum electrolytes (Na+, Mg2+ K+, Cl−, and Ca2+), total protein, urea, ɣ-glutamyl transferase (GGT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), albumin, total and conjugated bilirubin between the treatment and the control group. However, there were changes in creatinine, urea, and cholesterol. In the in vitro assays, ECE and ECAgNPs showed IC50 values of 70.87±2.99 and 138.8±3.98 µg/mL respectively against MDA-MB-231 cells compared to paclitaxel, which showed an IC50 value of 80 ng/mL. Conclusion The results showed that the LD50 of the ECE and ECAgNPs in Wister rats was determined to be greater than 2000 mg/kg body weight. The aqueous extract also showed more cytotoxic than the ECAgNPs suggesting that the toxic compounds in aqueous extract were involved in the capping of the AgNPs.


2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Dan Zhang ◽  
Lihong Tan ◽  
Ling Yao ◽  
Wei Tao ◽  
Ruixue Gong ◽  
...  

Lagotis brevituba Maxim is a perennial species distributed in the highlands of China, which has been used for more than 2000 years as a traditional Tibetan medicinal plant. However, no attention has been paid to the antioxidant activities of Lagotis brevituba Maxim in vitro or in vivo. Thus, this study aimed to evaluate the in vitro and in vivo antioxidant activity of Lagotis brevituba Maxim against radiation-induced damage as well as the systematic chemical components. To explore the relationship between the antioxidant activity and extraction solvent, Lagotis brevituba Maxim was extracted with three different solvents: methanol, water, and acetone. In antioxidant assays in vitro, the water extract had the strongest reducing power, 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity compared with the methanol and acetone extracts. However, the methanol extract was more potent in the β-carotene/linoleic acid cooxidation assay. In antioxidant assays in vivo, mice that were exposed to 6.0 Gy60Co γ-ray whole-body radiation on day 15 after administration of Lagotis brevituba Maxim decreased their level of malondialdehyde (MDA) in a dose-dependent manner compared with the control group, indicating that Lagotis brevituba Maxim had favorable antioxidant activities in vivo. In addition, a total of 44 compounds were tentatively identified by liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS), including 19 flavonoids, 14 phenols, 8 phenylethanoid glycosides, 2 iridoid glycosides, and 1 carbohydrate. We obtained 25 compounds from plants in the genus Lagotis for the first time. These results suggested that Lagotis brevituba Maxim had potent antioxidant activity and could be explored as a novel natural antioxidant.


1959 ◽  
Vol 197 (4) ◽  
pp. 725-729
Author(s):  
Durwood J. Smith ◽  
Robert C. Parker ◽  
Calvin Hanna ◽  
Henry E. Curley

A battery of in vivo and in vitro tests of cardiovascular performance were used to assess the effects of whole-body gamma radiation (cobalt-60) upon the cardiovascular system of dogs. A new method for study of the pressure-volume relations of isolated surviving arteries is described. Groups of six beagles were exposed to 30 r and 100 r 22 months before death and compared with littermate controls. No differences between irradiated and control dogs could be demonstrated. Eight mongrel dogs received 300 r 30 days before death and were compared with five mongrel controls. The only significant difference observed was in the pressure-volume curves of arteries from irradiated dogs, these vessels having a greater initial tone than control arteries. It is concluded that 30 r and 100 r of whole-body gamma radiation have no demonstrable effect upon the cardiovascular system of dogs irradiated 22 months before study, but that 300 r of gamma radiation does produce a significant abnormality of blood vessels.


Sign in / Sign up

Export Citation Format

Share Document