Deferoxamine preconditioning to restore impaired HIF-1α-mediated angiogenic mechanisms in adipose-derived stem cells from STZ-induced type 1 diabetic rats

Objectives: Both excessive and insufficient angiogenesis are associated with progression of diabetic complications, of which poor angiogenesis is an important feature. Currently, adipose-derived stem cells (ADSCs) are considered to be a promising source to aid therapeutic neovascularization. However, functionality of these cells is impaired by diabetes which can result from a defect in hypoxia-inducible factor-1 (HIF-1), a key mediator involved in neovascularization. In the current study, we sought to explore effectiveness of pharmacological priming with deferoxamine (DFO) as a hypoxia mimetic agent, to restore the compromised angiogenic pathway, with the aid of ADSCs derived from streptozotocin (STZ)-induced type 1 diabetic rats ('diabetic ADSCs'). Materials and methods: Diabetic ADSCs were treated with DFO and compared to normal and non-treated diabetic ADSCs for expression of HIF-1α, VEGF, FGF-2 and SDF-1, at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activity of matrix metalloproteinases -2 and -9 were measured using a gelatin zymography assay. Angiogenic potential of conditioned media derived from normal, DFO-treated and non-treated diabetic ADSCs were determined by in vitro (in HUVECs) and in vivo experiments including scratch assay, three-dimensional tube formation testing and surgical wound healing models. Results: DFO remarkably enhanced expression of noted genes by mRNA and protein levels and restored activity of matrix metalloproteinases -2 and -9. Compromised angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by DFO both in vitro and in vivo experiments. Conclusion: DFO preconditioning restored neovascularization potential of ADSCs derived from diabetic rats by affecting the HIF-1α pathway. © 2015 John Wiley & Sons Ltd

Comparison of Yarrowia lipolytica and Pichia pastoris cellular response to different agents of oxidative stress

Yeast cells exposed to adverse conditions employ a number of defense mechanisms in order to respond effectively to the stress effects of reactive oxygen species. In this work, the cellular response of Yarrowia lipolytica and Pichia pastoris to the exposure to the ROSinducing agents’ paraquat, hydrogen peroxide, and increased air pressure was analyzed. Yeast cells at exponential phase were exposed for 3 h to 1 mM paraquat, to 50 mM H2O2, or to increased air pressure of 3 or 5 bar. For both strains, the cellular viability loss and lipid peroxidation was lower for the cells exposed to increased air pressure than for those exposed to chemical oxidants. The glutathione induction occurred only in Y. lipolytica strain and reached the highest level as a response to PQ exposure. In general, antioxidant enzymes were more expressed in Y. lipolytica than in P. pastoris. The enzyme superoxide dismutase was induced in both strains under all the oxidant conditions but was dependent on the cellular growth phase, being undetectable in non-growing cells, whereas glutathione reductase was more induced in those conditions. Hydrogen peroxide was the most efficient inducer of catalase. Both yeast cultures underwent no cellular growth inhibition with increased air pressure, indicating that these yeast species were able to adapt to the oxidative stressful environment.The authors acknowledge the financial support provided by "Fundacao para a Ciencia e Tecnologia" (Grant SFRH/BD/47371/2008)

WldS Reduces Paraquat-Induced Cytotoxicity via SIRT1 in Non-Neuronal Cells by Attenuating the Depletion of NAD

WldS is a fusion protein with NAD synthesis activity, and has been reported to protect axonal and synaptic compartments of neurons from various mechanical, genetic and chemical insults. However, whether WldS can protect non-neuronal cells against toxic chemicals is largely unknown. Here we found that WldS significantly reduced the cytotoxicity of bipyridylium herbicides paraquat and diquat in mouse embryonic fibroblasts, but had no effect on the cytotoxicity induced by chromium (VI), hydrogen peroxide, etoposide, tunicamycin or brefeldin A. WldS also slowed down the death of mice induced by intraperitoneal injection of paraquat. Further studies demonstrated that WldS markedly attenuated mitochondrial injury including disruption of mitochondrial membrane potential, structural damage and decline of ATP induced by paraquat. Disruption of the NAD synthesis activity of WldS by an H112A or F116S point mutation resulted in loss of its protective function against paraquat-induced cell death. Furthermore, WldS delayed the decrease of intracellular NAD levels induced by paraquat. Similarly, treatment with NAD or its precursor nicotinamide mononucleotide attenuated paraquat-induced cytotoxicity and decline of ATP and NAD levels. In addition, we showed that SIRT1 was required for both exogenous NAD and WldS-mediated cellular protection against paraquat. These findings suggest that NAD and SIRT1 mediate the protective function of WldS against the cytotoxicity induced by paraquat, which provides new clues for the mechanisms underlying the protective function of WldS in both neuronal and non-neuronal cells, and implies that attenuation of NAD depletion may be effective to alleviate paraquat poisoning

The Inhibitory Effect of Captopril on Paraquat Toxicity in Mitochondria Isolated from the Rat Liver

Abstract: Background: The aim of the present study was to show the capability of captopril as a thiol ACEi (angiotensin converting enzyme inhibitor),in suppressing mitochondrial toxicity due to paraquat. Method: In this study, rats liver mitochondria were isolated with buffer using refrigerated centrifuge. In order to obtain the minimum toxic dose of paraquat and the effective dose of captopril, different concentrations of paraquat (1 to 100mM)and captopril (0.08 to 1mM)were investigated by determining LC50 , viability indices, lipid peroxidation, mitochondrial swelling, catalase activity, GSH and GSSG. Results: Simultaneous treatment of mitochondria with captopril (0.08mM) and paraquat (5mM) significantly ameliorate the mitochondrial toxicity of paraquat (5mM) alone. Our results show that captopril is a effective antioxidant. The antioxidative action of captopril appears to be attributable to the sulphahydryl group (SH) in the compound. This effect may be due to captopril abilities to scavenge reactive oxygen species. Conclusion: Our results indicate that Captopril can ameliorate oxidative stress induced by paraquat and therefore, can be used for the prevention and treatment of diseases caused by environmental toxins. Keywords: Paraquat, Rat liver Mitochondria, Captopril, Oxidative stres

INFLUENCES OF THIAMINE AND/OR ASCORBIC ACID ON LEAD INTOXICATION

The effects of thiamine, ascorbic acid ami their combination an workers who are continuously exposal to lead has been investigated. In this study 60 persons in a Battery industry was selected and divided into four equal groups. Group I received placebo, group II thiamine (300 mg), group III ascorbic acid (250 mg) anil group IV thiamine (300 mg) plus ascorbic acid (250 mg) three times a day (Orally). At beginning of the study and after one month of above drug regimen; blood, urine and a questionnaire about their clinical signs were examined. 'there were no significant differences between blood anil urine lead level in all groups after treatment. Zinc protoporphyrin (zpp) level showed a significant reduction in ascorbic acid treated group (group III) as compared to pretreatment. Clinical manifestation improved in the group that received both vitamins (group IV). However, from a clinical stand point, it appears the usage of these vitamins may have a beneficial effects in lead occupational exposure

Determining urine sample mutagenicity ratio using Ames test: Tehran forensic medicine laboratory personnels

"n Normal 0 false false false EN-GB X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Cancer prevention besides detection and treatment has a very important role in control of cancer disease. Since some chemical compounds that are used in laboratories, especially in pathology laboratory are potentially mutagens, lab assistances that are working with chemicals such as Benzene, Xylazine and Formaldehyde for long period of time may be exposed to overload of these carcinogens. Therefore, it is necessary to use an indicator for detecting these occupational exposures. Ames test has been recommended in biomonitoring of environment that has high risk carcinogenicity characteristic."n"nMethods: A total of fifty seven urine samples of forensic medicine laboratory personnel's were extracted by C18 column and then tested by TA100 and TA98 standard strains of Ames assay. Each sample was analyzed with and without activator to detect mutagen and promutagen materials."n"nResults: Levels of mutagenicity were found by TA98 strain without activator in one case as well as with activator in two cases of urine samples of pathology laboratory personnel's. These cases were working in laboratory for long time in all of the workdays."n"nConclusion: Personnel's working in pathology laboratories may have greater risk of cancer and should be take care from these occupational exposures

Radio-protective effects of melatonin against irradiation-Induced oxidative damage in rat peripheral blood

During radiotherapy, ionizing irradiation interacts with biological systems to produce free radicals, which attacks various cellular components. The hematopoietic system is well-known to be radiosensitive and its damage may be life-threatening. Melatonin synergistically acts as an immunostimulator and antioxidant. In this study we used a total of 120 rats with 20 rats in each group. Group 1 did not receive melatonin or irradiation (Control group), Group 2 received only 10 mg/kg melatonin (Mel group), Group 3 exposed to dose of 2 Gy irradiation (2 Gy Rad group), Group 4 exposed to 8 Gy irradiation (8 Gy Rad group), Group 5 received 2 Gy irradiation plus 10 mg/kg melatonin (Mel +2 Gy Rad group) and Group 6 received 8 Gy irradiation plus 10 mg/kg melatonin (Mel+8 Gy Rad group). Following exposure to radiation, five rats from each group were sacrificed at 4, 24, 48 and 72 h. Exposure to different doses of irradiation resulted in a dose-dependent decline in the antioxidant enzymes activity and lymphocyte count (LC) and an increase in the nitric oxide (NO) levels of the serum. Pre-treatment with melatonin (10 mg/kg) ameliorates harmful effects of 2 and 8 Gy irradiation by increasing lymphocyte count(LC) as well as antioxidant enzymes activity and decreasing NO levels at all time-points. In conclusion 10 mg/kg melatonin is likely to be a threshold concentration for significant protection against lower dose of 2 Gy gamma irradiation compared to higher dose of 8 Gy. Therefore, it seems that radio-protective effects of melatonin are dose-dependent. © 2011 Associazione Italiana di Fisica Medica

Evaluation of Some Natural Zeolites and Their Relevant Synthetic Types as Sorbents for Removal of Arsenic from Drinking Water

The purpose of this study was to find a relatively inexpensive method for removal of arsenate and arsenite from drinking water. The capability of Iranian natural clinoptilolites, relevant synthetic zeolites A and P and Iron(П) modified of them was investigated for the uptake of arsenic anions from drinking water. Data obtained from ion-exchange using batch (static) technique showed that among the investigated zeolites, modified synthetic zeolite A was the most selective sorbent for removal of arsenic. In this study, the influence of factores including temperature, arsenic concentration, pH and zeolite particle size on removal of arsenic species from water was also determined and studied