Association of prooxidant-antioxidant disorders with the development of morphofunctional disorders in rats with subtotal cerebral ischemia

The aim of the study was to investigate morphofunctional disorders of neurons in the cerebral cortex and changes in the prooxidant-antioxidant state in rats after subtotal cerebral ischemia. Material and methods. The experiments were performed on 20 white outbred male rats. Surgical interventions were carried out under intravenous thiopental anesthesia (40–50 mg/kg). Subtotal cerebral ischemia was simulated by both common carotid arteries ligation. Animals were decapitated after 60 minutes of ischemia. Morphological and functional changes in the neurons of the parietal cortex and hippocampal CA1 field, and intensity of free radical oxidative processes (content of thiobarbituric acid reactive substances and thiol-disulfide system components) in brain homogenates were studied. Results and discussion. Brain ischemia has been followed by oxidative stress in brain tissue. The cellular metabolism has been disturbed under the oxidative stress that leads to a water-electrolyte imbalance, manifested by deformation of neuron bodies, wrinkling, and swelling. The changes in parietal cortex are to a greater extent expressed, as the neurons are more sensitive to oxygen deficiency

Morphological disturbances of rat parietal cortex and hippocampus neurons in the dynamics steady subtotal ischemia of the brain

The purpose of the work is to analyze changes in the morphological characteristics of neurons of phylogenetical different parts of the cerebral cortex (parietal cortex and hippocampus) of rats at different periods in the dynamics of stepwise subtotal experimental cerebral ischemia. Methods. The experiments were performed on 42 males of outbred white rats. Step subtotal cerebral ischemia was performed as follows: first, one common carotid artery was ligated, simulating partial ischemia. Then, with an interval of 1 day (subgroup 1), 3 days (subgroup 2) or 7 days (subgroup 3), the second common carotid artery was ligated. Results. A microscopic study of the size, shape, degree of chromatophilia of the cytoplasm and the content of ribonucleoproteins in pyramidal neurons of phylogenetically different parts of the cerebral cortex have shown the dependence of the severity of brain damage on the interval between the cessation of blood flow in both carotid artery. Adaptation was better with a 7-day interval between dressings, while the ligation with an interval of 1 day, the degree of morphological changes was maximum indicating a lack of resources for the implementation of adaptation mechanisms

Antioksidativno djelovanje NSAID hidroksamskih kiselina

In the present study, seven hydroxamic acid derivatives of nonsteroidal anti-inflammatory drugs (NSAIDs) (ibuprofen, fenoprofen, ketoprofen, indomethacin and diclofenac) were found to possess significant antioxidant, radical scavenging and metal chelating activities. The most active antioxidant and radical scavenger was N-methylhydroxamic acid of diclofenac (ANT = 88.0 % and EC50 = 60.1 microg mL-1). The activity of the standard substance, butylated hydroxyanisole, in the two assays was ANT = 86.9 % and EC50 = 18.8 microg mL-1, respectively. Ibuproxam was the strongest iron chelator among investigated hydroxamic acids (EC50 = 255.6 microg mL-1), yet significantly weaker than the standard substance, EDTA (EC50 = 29.1 microg mL-1). It seems that different mechanism is involved in metal chelating activity than in antioxidant and radical scavenging activity. Antioxidant and radical scavenging activities may be connected with conjugation of the nitrogen lone electron pair with the carbonyl group. On the other hand, more hydrophilic substances tend to be better iron chelators.U radu je opisano antioksidativno djelovanje te sposobnost hvatanja slobodnih radikala i stvaranja kelata sedam hidroksamskih kiselina, derivata nesteroidnih protuupalnih lijekova ibuprofena, fenoprofena, ketoprofena, indometacina i diklofenaka. Najjače antioksidativno djelovanje i najjaču sposobnost hvatanja slobodnih radikala imala je N-metilhidroksamska kiselina diklofenaka (ANT = 88,0 % i EC50 = 60,1 g mL1). Vrijednosti za standardnu supstanciju, butilirani hidroksianisol, bile su: ANT = 86,9 % i EC50 = 18,8 g mL1. Derivat ibuprofena bio je najjači kelator među ispitivanim hidroksamskim kiselinama (EC50 = 255,6 g mL1), ali značajno slabiji od standardne supstancije, EDTA (EC50 = 29,1 g mL1). Pretpostavlja se da su različiti mehanizmi uključeni u keliranje metala i antioksidativno djelovanje, odnosno hvatanje slobodnih radikala. Antioksidativno djelovanje i sposobnost hvatanja slobodnih radikala moglo bi biti povezano s konjugacijom slobodnog para elektrona na dušiku s karbonilnom skupinom. S druge strane, hidrofilnije supstancije pokazale su se kao jači kelatori iona željeza

Mineral analysis of complete dog and cat foods in the UK and compliance with European guidelines

Mineral content of complete pet food is regulated to ensure health of the companion animal population. Analysis of adherence to these regulatory guidelines has not been conducted. Here, mineral composition of complete wet (n = 97) and dry (n = 80) canine and feline pet food sold in the UK was measured to assess compliance with EU guidelines. A majority of foods complied with ≥8 of 11 guidelines (99% and 83% for dry and wet food, respectively), but many failed to provide nutritional minimum (e.g. Cu, 20% of wet food) or exceeded nutritional maximum (e.g. Se, 76% of wet food). Only 6% (6/97) of wet and 38% (30/80) of dry food were fully compliant. Some foods (20–30% of all analysed) had mineral imbalance, such as not having the recommended ratio of Ca:P (between 1:1 to 2:1). Foods with high fish content had high levels of undesirable metal elements such as arsenic. This study highlights broad non-compliance of a range of popular pet foods sold in the UK with EU guidelines (94% and 61% of wet and dry foods, respectively). If fed exclusively and over an extended period, a number of these pet foods could impact the general health of companion animals

Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to compare plasma levels of antioxidants and oxidative stress biomarkers in head and neck squamous cell carcinoma (HNSCC) patients with healthy controls. Furthermore, the effect of radiotherapy on these biomarkers and their association with survival in HNSCC patients were investigated.</p> <p>Methods</p> <p>Seventy-eight HNSCC patients and 100 healthy controls were included in this study. Follow-up samples at the end of radiotherapy were obtained in 60 patients. Fifteen antioxidant biomarkers (6 carotenoids, 4 tocopherols, ascorbic acid, total antioxidant capacity, glutathione redox potential, total glutathione and total cysteine) and four oxidative stress biomarkers (total hydroperoxides, γ-glutamyl transpeptidase, 8-isoprostagladin F_2αand ratio of oxidized/total ascorbic acid) were measured in plasma samples. Analysis of Covariance was used to compare biomarkers between patients and healthy controls. Kaplan-Meier plots and Cox' proportional hazards models were used to study survival among patients.</p> <p>Results</p> <p>Dietary antioxidants (carotenoids, tocopherols and ascorbic acid), ferric reducing antioxidant power (FRAP) and modified FRAP were lower in HNSCC patients compared to controls and dietary antioxidants decreased during radiotherapy. Total hydroperoxides (d-ROMs), a marker for oxidative stress, were higher in HNSCC patients compared to controls and increased during radiotherapy. Among the biomarkers analyzed, high levels of plasma carotenoids before radiotherapy are associated with a prolonged progression-free survival (hazard rate ratio: 0.42, 95% CI: 0.20-0.91, p = 0.03). Additionally, high relative increase in plasma levels of d-ROMs (hazard rate ratio: 0.31, 95% CI: 0.13-0.76, p = 0.01) and high relative decrease in FRAP (hazard rate ratio: 0.42, 95% CI: 0.17-0.998, p = 0.05) during radiotherapy are also positively associated with survival.</p> <p>Conclusions</p> <p>Biomarkers of antioxidants and oxidative stress are unfavourable in HNSCC patients compared to healthy controls, and radiotherapy affects many of these biomarkers. Increasing levels of antioxidant biomarkers before radiotherapy and increasing oxidative stress during radiotherapy may improve survival indicating that different factors/mechanisms may be important for survival before and during radiotherapy in HNSCC patients. Thus, the therapeutic potential of optimizing antioxidant status and oxidative stress should be explored further in these patients.</p

Orally Active Multi-Functional Antioxidants Are Neuroprotective in a Rat Model of Light-Induced Retinal Damage

Progression of age-related macular degeneration has been linked to iron dysregulation and oxidative stress that induce apoptosis of neural retinal cells. Since both antioxidants and chelating agents have been reported to reduce the progression of retinal lesions associated with AMD in experimental animals, the present study evaluates the ability of multi-functional antioxidants containing functional groups that can independently chelate redox metals and quench free radicals to protect the retina against light-induced retinal degeneration, a rat model of dry atrophic AMD.Proof of concept studies were conducted to evaluate the ability of 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8) to reduce retinal damage in 2-week dark adapted Wistar rats exposed to 1000 lx of light for 3 hours. Assessment of the oxidative stress markers 4- hydroxynonenal and nitrotyrosine modified proteins and Thioredoxin by ELISA and Western blots indicated that these compounds reduced the oxidative insult caused by light exposure. The beneficial antioxidant effects of these compounds in providing significant functional and structural protection were confirmed by electroretinography and quantitative histology of the retina.The present study suggests that multi-functional compounds may be effective candidates for preventive therapy of AMD

The prognostic and predictive power of redox rotein expression for anthracycline-based chemotherapy response in locally advanced breast cancer

Neoadjuvant chemotherapy has become the standard of care for locally advanced primary breast cancer. Anthracycline-based regimens have proven to be one of the most effective treatments in this setting. As certain cytotoxic antineoplastic agents, such as anthracyclines, generate reactive oxygen species as a by-product of their mechanism of action, we examined whether redox protein expression was involved in the response to anthracycline-based chemotherapy and with clinical outcome. Pre treatment needle core biopsy and postanthracycline treatment tumour sections were analysed from 98 cases. In all, 32 individuals had a complete clinical response and 17 had a complete pathological response. Immunohistochemical staining was performed for eight redox proteins: thioredoxin, thioredoxin reductase thioredoxin interacting protein (TxNIP), glutathione S-transferase (GST) p, h and a, catalase and manganese superoxide dismutase. GST p (P¼0.05) and catalase (P¼0.045) were associated with pathological complete response in pre-chemotherapy samples. TxNIP (P¼0.017) and thioredoxin reductase (P¼0.022) were independent prognostic factors for distant metastasis free survival and TxNIP for overall survival (P¼0.014). In oestrogen receptor negative patients that are known to have a poor overall survival, a considerably worse prognosis was seen in cases that exhibited low expression of TxNIP (P¼0.000003), stratifying patients into more defined groups. This study indicates the importance of redox regulation in determining breast cancer response to anthracycline-based chemotherapy and provides ways of further stratifying pre-chemotherapy patients to potentially allow more tailored treatments

Ne-termalni biopokazatelji izloženosti radiofrekvencijskom/mikrovalnom zračenju

This article gives a review or several hypotheses on the biological effects of non-thermal radiofrequency/microwave (RF/MW) radiation and discusses our own findings from animal and in vitro studies performed over the last decade. We have found that RF/MW radiation disturbs cell proliferation and leads to cell differentiation in the bone marrow, which is reflected in the peripheral blood of rats. Repeated RF/MW radiation can also temporarily disrupt melatonin turnover. The observed changes seem to be a sign of adaptation to stress caused by irradiation rather than of malfunction. The article looks further into the basic mechanisms of RF/MW biological action, including cell growth parameters, colony-forming ability, viability, and the polar and apolar protein cytoskeleton structures. The observed reversible cell changes significantly obstructed cell growth. In contrast to the apolar intermediate proteins, the intracellular polar microtubule and actin fibres were damaged by radiation in a time-dependent manner. These signifi cantly altered parameters can be considered as the biomarkers of exposure. Future research should combine dosimetry, experimental studies, and epidemiological data.Svrha rada je prikaz više hipoteza o biološkom djelovanju ne-termalnih razina radiofrekventnog/mikrovalnog (RF/MW) zračenja i rasprava o rezultatima vlastitih istraživanja na životinjama i in vitro. Istraživanje djelovanja elektromagnetskih polja na organizam uključilo je proučavanje hematopoieze u štakora povremeno izloženih ne-termalnom radiofrekventnom/mikrovalnom (RF/MW) zračenju tijekom supkroničnog pokusa. Rezultati su pokazali neravnotežu u proliferaciji i diferencijaciji stanica koštane srži što se odrazilo na stanične parametre u krvi štakora. U primijenjenim uvjetima zračenja nađeno je da RF/MW može privremeno destabilizirati metabolizam melatonina bez štetnog utjecaja na zdravlje životinja. Razmatrana je mogućnost aktivacije prilagodbenog mehanizma na stres izazvan zračenjem jer smatramo da su nađene promjene prije znak adaptacije nego štetnog učinka zračenja. Pristup temeljnim mehanizmima biološkog djelovanja RF/MW zračenja uključio je istraživanje parametara staničnog rasta, sposobnosti stvaranja kolonija, vijabilnosti te polarnih i nepolarnih proteinskih struktura citoskeleta nakon ozračivanja stanica. Reverzibilne promjene staničnih svojstava koje su nađene upućuju na značajnu opstrukciju staničnog rasta. Za razliku od nepolarnih intermedijarnih proteina, unutarstanična polarna vlakna mikrotubula i aktina su, ovisno o vremenu izloženosti, pokazala značajna oštećenja uzrokovana zračenjem. Statistički značajno promijenjeni parametri smatrani su biomarkerima izloženosti. Istaknuta je potreba za budućim istraživanjima koja uključuju epidemiološke, laboratorijske i dozimetrijske studije