Several pre-clinical and clinical studies have demonstrated zoledronic acid (Zol), which regulates the mevalonate pathway, has efficient anti-cancer effects. Zol can also induce autophagy. The aim of this study is to add new understanding to the mechanism of autophagy induction by Zol. LC3B-II, the marker for autophagy was increased by Zol treatment in breast cancer cells. Autophagosomes induced by Zol were visualized and quantified in both transient (pDendra2-hLC3) and stable MCF-7- GFP-LC3 cell lines. Acidic vesicular organelles were quantified using acridine orange. Zol induced a dose and time dependent autophagy. Treatment of Zol increased oxidative stress in MCF-7 cells, which was reversed by GGOH or anti-oxidants. On the other hand, treatment with GGOH or anti-oxidants resulted in decreased levels of LC3B-II. Further, the induced autophagy was irreversible, as the washout of Zol after 2 h or 24 h resulted in similar levels of autophagy, as induced by continuous treatment after 72 h. Thus, it can be summarized that Zol can induce a dose dependent but irreversible autophagy, by its effect on the mevalonate pathway and oxidative stress. This study adds to the understanding of the mechanism of action of Zol, and that it can induce autophagy at clinically relevant shorter exposure times in cancer cells., V. K. M. Khandelwal, L. M. Mitrofan, J. M. T. Hyttinen, K. R. Chaudhari, R. Buccione, K. Kaarniranta, T. Ravingerová, J. Mönkkönen., and Obsahuje bibliografii
Recent studies demonstrated remote effects of renal ischemia/reperfusion (I/R) injury on some organs such as brain, liver, and lungs. We investigated the effects of renal I-R injury on function, histology and oxidative stress state of pancreas. Twenty -four male adult Sprague-Dawley rats were divided equally into 2 groups; sham group: rats underwent midline laparotomy and dissection of renal pedicles without renal ischemia, and ischemic group: rats underwent bilateral renal ischemia for 45 min. Renal functions (serum creatinine and BUN), pancreatic functions (serum amylase, lipase and insulin) and fasting blood glucose were measured at 2 h, 1 day, 3 days and 7 days after ischemia. Also, pancreatic histology and malondialdehyde (MDA), catalase and reduced glutathione (GSH) were examined at 2 h and 7 days after ischemia. The ischemic rats showed significant increase in serum creatinine and BUN with significant increase in serum amylase and lipase at 2 h, 1 day and 3 days after ischemia. Blood glucose and fasting insulin showed no significant change apart from significant increase in insulin in sham group at 1 day after ischemia. Pancreas isolated from ischemic rats showed significant increase in histopathological damage score and significant increase in MDA and catalase enzyme with decrease in GSH. In conclusion, bilateral renal ischemia for 45 min caused significant impairment of pancreatic functions and histology. This might be due to deficiency of antioxidant and increased lipid peroxidations in pancreatic tissues., A. M. Hussein ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Diabetes mellitus is relatively frequently associated with fatty liver disease. Increased oxidative stress probably plays an important role in the development of this hepatopathy. One of possible sources of reactive oxygen species in liver is peroxisomal system. There are several reports about changes of peroxisomal enzymes in experimental diabetes, mainly enzymes of fatty acid oxidation. The aim of our study was to investigate the possible changes of activities of liver peroxisomal enzymes, other than enzymes of beta-oxidation, in experimental diabetes mellitus type 2. Biochemical changes in liver of experimental animals suggest the presence of liver steatosis. The changes of serum parameters in experimental group are similar to changes in serum of patients with non-alcoholic fatty liver disease. We have shown that diabetes mellitus influenced peroxisomal enzymes by the different way. Despite of well-known induction of peroxisomal beta-oxidation, the activities of catalase, aminoacid oxidase and NADH-cytochrome b5 reductase were not significantly changed and the activities of glycolate oxidase and NADP-isocitrate dehydrogenase were significantly decreased. The effect of diabetes on liver peroxisomes is probably due to the increased supply of fatty acids to liver in diabetic state and also due to increased oxidative stress. The changes of metabolic activity of peroxisomal compartment may participate on the development of diabetic hepatopathy., L. Turecký, V. Kupčová, E. Uhlíková, V. Mojto., and Obsahuje bibliografii
High levels of catecholamines in pheochromocytoma (PHEO) are associated with risk of cardiovascular complications. In this study, we looked for potential differences in markers of oxidative stress – vitamin C, superoxide dismutase (SOD) and malondialdehyde (MDA) in PHEO before and after the operation. We studied 18 subjects with PHEO who were examined before and approximately one year after the successful tumor removal (free of disease). All subjects had elevated urinary epinephrine and/or norepinephrine levels before the operation. Vitamin C levels increased significantly after the operation from 61±27 to 77±20 μmol/l (P=0.02), and MDA decreased significantly after the tumor removal from 2.6±0.4 to 2.0±0.6 μmol/l (P=0.01). However, no changes were found in SOD activity before and after the operation. In conclusion, increased catecholamine production in PHEO is accompanied by decreased levels of vitamin C and increased levels of MDA which may indicate the activation of oxidative stress in PHEO. Successful operation was associated with lowering of oxidative stress by using both biomarkers. On the contrary, no changes in SOD activity before and after the tumor removal were noted., H. Turková, ... [et al.]., and Obsahuje seznam literatury
Water deficit is an important exogenous factor that enhances the influx of sucrose into sugarcane (Saccharum spp.) stem internodes during ripening, when photosynthetic ability in supplying sinks is essential. The aim of this study was to test the hypothesis that drought tolerance in sugarcane is associated with an effective antioxidant protection during the ripening phase that might maintain a favorable redox balance in chloroplasts and protect photosynthesis under drought conditions. Two commercial sugarcane varieties, IACSP94-2094 (tolerant) and IACSP96-2042 (sensitive), with contrasting behavior under water deficit, were subjected to water withholding during the ripening stage. Our results revealed that the tolerant variety was less affected by water deficit, maintaining photosynthesis for a longer period and showing a faster recovery after rehydration as compared to the sensitive one. As consequence, the tolerant variety faced lesser excess of light energy at PSII. The maintenance of photosynthesis under water deficit and its fast recovery after rehydration resulted in the lower leaf H2O2 concentration and favorable redox status in the drought-tolerant genotype, which was associated with stimulation of superoxide dismutase during ripening. Our results also revealed that ferric superoxide dismutase isoforms were strongly enhanced under drought conditions, playing an important role in chloroplast redox homeostasis., C. R. G. Sales, P. E. R. Marchiori, R. S. Machado, A. V. Fontenele, E. C. Machado, J. A. G. Silveira, R. V. Ribeiro., and Obsahuje seznam literatury
When cells get metals in small excess, mechanisms of avoidance occur, such as exclusion, sequestration, or compartmentation. When the excess reaches sub-lethal concentrations, the oxidative stress, that toxic metals trigger, leads to persistent active oxygen species. Biomolecules are then destroyed and metabolism is highly disturbed. At the chloroplast level, changes in pigment content and lipid peroxidation are observed. The disorganized thylakoids impair the photosynthetic efficiency. The Calvin cycle is also less efficient and the photosynthetic organism grows slowly. When an essential metal is given together with a harmful one, the damages are less severe than with the toxic element alone. Combined metals and phytochelatins may act against metal toxicity. and M. Bertrand, I. Poirier.
Selected light wavebands promote plant development and/or the biosynthesis of targeted metabolites. This work offers new insights on the effects of red (R), green (G), blue (B), and white (W - R:G:B; 1:1:1) LED light supplementation on physiochemical traits of strawberry leaves. Gas exchange and chlorophyll fluorescence parameters, photosynthetic pigments, and superoxide anion (*O2-) content were analysed in plants grown for 1 (T1) and 17 (T17) d with light supplementations. At T1, light supplementations resulted in the enhancement of the de-epoxidation state of xanthophylls and nonphotochemical quenching, but no changes were observed in maximal photosynthetic rate (PNmax), irrespective of light spectra. At T17, xanthophyll contents remained higher only in R-supplemented plants. Overall, W light resulted in higher photosynthesis, whilst R and B light depressed PNmax values and promoted *O2- formation at T17. G light did not induce variations in photosynthetic traits nor induced oxidative stress at both T1 and T17.
Acute lung injury (ALI) caused by lipopolysaccharide (LPS) is a common, severe clinical syndrome. Injury caused by inflammation and oxidative stress in vascular endothelial and alveolar epithelial cells is a vital process in the pathogenesis of ALI. Toll-like receptor 9 (TLR9) is highly expressed in LPS-induced ALI rats. In this study, Beas-2B human pulmonary epithelial cells and A549 alveolar epithelial cells were stimulated by LPS, resulting in the upregulation of TLR9 in a concentrationdependent manner. Furthermore, TLR9 overexpression and interference vectors were transfected before LPS administration to explore the role of TLR9 in LPS-induced ALI in vitro. The findings revealed that inhibition of TLR9 reduced inflammation and oxidative stress while suppressing apoptosis of LPS-induced Beas-2B and A549 cells, whereas TLR9 overexpression aggravated these conditions. Moreover, TLR9 inhibition resulted in downregulated protein expression of myeloid differentiation protein 88 (MyD88) and activator activator protein 1 (AP-1), as well as phosphorylation of nuclear factor-κB (NF-κB), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK). The phosphorylation of extracellular-regulated protein kinases 1/2 was upregulated compared to that of cells subjected to only LPS administration, and this was reversed by TLR9 overexpression. These results indicate that inhibition of TLR9 plays a protective role against LPS-induced inflammation and oxidative stress in Beas-2B and A549 cells, possibly via the MyD88/NF-κB and MyD88/MAPKs/AP-1 pathways.
Chronic kidney disease (CKD) represents a serious public health problem with increasing prevalence and novel approaches to renal protection are continuously under investigation. The aim of this study was to compare the effect of melatonin and angiotensin II type 2 receptor agonist compound 21 (C21) to angiotensin converting enzyme inhibitor captopril and angiotensin II type 1 receptor blocker olmesartan on animal model of doxorubicin nephrotoxicity. Six groups of 3-month-old male Wistar rats (12 per group) were treated for four weeks. The first group served as a control. The remaining groups were injected with a single dose of doxorubicin (5 mg/kg i.v.) at the same day as administration of either vehicle or captopril (100 mg/kg/day) or olmesartan (10 mg/kg/day) or melatonin (10 mg/kg/day) or C21 (0.3 mg/kg/day) was initiated. After four week treatment, the blood pressure and the level of oxidative stress were enhanced along with reduced glomerular density and increased glomerular size. Captopril, olmesartan and melatonin prevented the doxorubicin-induced increase in systolic blood pressure. All four substances significantly diminished the level of oxidative burden and prevented the reduction of glomerular density and modestly prevented the increase of glomerular size. We conclude that captopril, olmesartan, melatonin and C21 exerted a similar level of renoprotective effects in doxorubicin-induced nephrotoxicity., J. Hrenák ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Pulmonary hypertension resulting from chronic hypoxia is at least partly caused by the increased production of reactive oxygen species (ROS). The goal of the presented study was to investigate the dynamics and the site of production of ROS during chronic hypoxia. In our study Wistar rats were kept for 1, 4 and 21 days in an isobaric hypoxic chamber (FiO2=0.1), while controls stayed in normoxia. We compared NO production in expired air, plasma and perfusate drained from isolated rat lungs and measured superoxide concentration in the perfusate. We also detected the presence of superoxide products (hydrogen peroxide and peroxynitrite) and the level of ROS-induced damage expressed as the concentration of lipid peroxydation end products. We found that the production and release of ROS and NO during early phase of chronic hypoxia has specific timing and differs in various compartments, suggesting the crucial role of ROS interaction for development of hypoxic pulmonary hypertension., D. Hodyc ... [et al.]., and Obsahuje seznam literatury