Parameters of Oxidative Stress and Activity of Antioxidant Enzymes in the Saliva of Patients with Type 1 Diabetes Mellitus.

Glucose concentration in the saliva is increased in type 1 diabetes mellitus. This parameter directly correlates with markers of the disease in the blood serum. Increased concentration of 8-oxo-2'-deoxyguanosine (8-OHdG) and diene conjugates, markers of oxidative stress, and reduced activities of superoxide dismutase and catalase were also observed in this pathology. Correlation analysis revealed a strong positive correlation between glucose concentration and the levels of oxidative stress markers and a negative correlation between activity of antioxidant enzymes and glucose concentration. The results indicate that the level of 8-OHdG, diene conjugates, and superoxide dismutase and catalase activities can serve as diagnostic markers of pathophysiological changes in the body in type 1 diabetes mellitus.

1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline exerts a neuroprotective effect and normalises redox homeostasis in a rat model of cerebral ischemia/reperfusion.

Ischemia is one of the main etiological factors of stroke and is associated with the development of energy deficiency, oxidative stress, and inflammation. An abrupt restoration of blood flow, called reperfusion, can worsen the effects of ischemia. In our study, we assessed the neuroprotective potential of 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (BHDQ) in cerebral ischemia/reperfusion (CIR) in rats. Wistar rats, divided into 4 groups were used in the study: sham-operated animals; animals with CIR caused by occlusion of the common carotid arteries and subsequent removal of the occlusions; rats treated with BHDQ at a dose of 50 mg/kg in the presence of pathology; sham-operated animals treated with BHDQ. The analysis of the state of energy metabolism in the brain, the level of the S100B protein and the histological assessment of the brain tissue were carried out. The antioxidant potential of BHDQ was assessed by measuring biochemiluminescence parameters, analysing the level of 8-isoprostane, products of lipid and protein oxidation, concentration of α-tocopherol and citrate, and aconitate hydratase activity during CIR in rats. A study of the effect of BHDQ on the regulation of the enzymatic antioxidant system and the inflammatory processes was performed. We demonstrated that BHDQ has a neuroprotective effect in CIR, reducing histopathological changes in the brain, normalizing pyruvate and lactate concentrations, and the transcripts level of Hif-1α gene. The positive effect of BHDQ was probably due to its antioxidant and anti-inflammatory activity, manifested in a decrease in the parameters of the oxidative stress, decreased mRNA of proinflammatory cytokines and NF-κB factor genes. In addition, BHDQ reduced the load on antioxidant protection enzymes, contributing to a change in their activities, decreased the level of antioxidant gene transcripts and expression of Nrf2 and Foxo1 factors toward control. Thus, BHDQ exhibited a neuroprotective effect due to a decrease in the level of oxidative stress and inflammation and the normalization of redox homeostasis on CIR in rats.

Two-color interferometer for study of dense low-ionized plasma on the target in high-power pulse linear accelerator.

A two-color infrared interferometer has been developed for the investigation of high-density weakly ionized tantalum plasma in x-ray complexes based on linear induction accelerators (1.6 kA electron beam current, 4.6 MeV energy, and 100 ns pulse duration). Simultaneous probing at two different wavelengths makes it possible to independently measure the density of neutral and electron components. The interferometer uses wavelength values of 1.064 µm (Nd:YAG laser) and 10.6 µm (CO2 laser). To attenuate the effect of sample beam refraction in inhomogeneous plasma, the interferometer used a refraction suppression scheme composed of spherical mirrors focusing the object beam into the region occupied by the plasma. In addition, the power of the sample beam transmitted through the plasma was controlled in order to analyze whether there was a distortion of the interference pattern because of strong sample beam refraction and absorption in the plasma cloud. To calibrate the initial phase shift of the probe radiation, a movable mirror mounted on a piezoelectric element and oscillating according to a harmonic law with amplitude greater than the laser wavelengths was used. In initial experiments, the parameters of target plasma registered by this interferometer are as follows: the linear density of neutrals reached 1.5 · 1017 cm-2, and the degree of ionization was of the order of 10-2. The target plasma expansion velocity is determined as ∼6 km/s.

Neuroprotective effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline mediated via regulation of antioxidant system and inhibition of inflammation and apoptosis in a rat model of cerebral ischemia/reperfusion.

The aim of the study was the assessment of the neuroprotective potential of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (DHQ) and its effect on inflammation, apoptosis, and transcriptional regulation of the antioxidant system in cerebral ischemia/reperfusion (CIR) in rats. The CIR rat model was constructed using the bilateral common carotid artery occlusion followed by reoxygenation. DHQ was administered at a dose of 50 mg/kg for three days. Histological staining was performed using hematoxylin and eosin. The level of S100B protein, 8-hydroxy-2-deoxyguanosine, and 8-isoprostane was assessed using an enzyme immunoassay. The intensity of apoptosis was assessed based on the activity of caspases and DNA fragmentation. The activity of enzymes was measured spectrophotometrically, the level of gene transcripts was assessed by real-time PCR. DHQ reduced the histopathological changes and normalized levels of S100B, lactate, pyruvate, and HIF-1 mRNA in the CIR rat model. In addition, DHQ decreased the oxidative stress markers in animals with a pathology. The tested compound also inhibited inflammation by decreasing the activity of myeloperoxidase, expression of interleukins and Nfkb2. DHQ-treated rats with CIR showed decreased caspase activity, DNA fragmentation, and AIF expression. DHQ changed activity of antioxidant enzymes to the control values, decreased the expression of Cat, Gsr, and Nfe2l2, which was overexpressed in CIR, and activated the expression of Sod1, Gpx1, Gsta2, and Foxo1. DHQ showed a neuroprotective effect on CIR in rats. The neuroprotective effect involve mechanisms such as the inhibition of oxidative stress, leading to a reduction in the inflammatory response and apoptosis and the modulation of the antioxidant defense components.

[Effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on the intensity of free radical processes and the activity of oxidative metabolism enzymes under toxic liver injury in rats]. / Vozdeistvie 6-gidroksi-2,2,4-trimetil-1,2-digidro-khinolina na intensivnost' svobodnoradikal'nykh protsessov i aktivnost' fermentov okislitel'nogo metabolizma pri toksicheskom porazhenii pecheni u krys.

The effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of hepatocytes cytolysis (aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase), parameters reflecting the state of oxidative status (intensity of biochemical luminescence and the content of diene conjugates), and the activity of oxidative metabolism enzymes (aconitate hydratase, glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) was studied in rats with CCl4-induced liver injury. The results obtained in the course of the work demonstrated the ability of the test compound to reduce the severity of oxidative stress and liver cells damage, as well as to change the activity of aconitate hydratase and NADP-generating enzymes in the direction of control values. 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline was more effective in normalizing CCl4-induced changes of the analyzed parameters that Carsil used as a reference compound. The tendency to normalize the state of oxidative status and enzyme activity of oxidative metabolism can attributed to hepatoprotective and antioxidant properties of the tested compound.

[The effect of biguanide derivatives on oxidative stress in rats with hyperglycemia]. / Vozdeistvie biguanidinovykh proizvodnykh na razvitie oksidativnogo stressa pri giperglikemii u krys.

The effect of the synthetic biguanide derivatives N-[imino(1-piperidinyl)methyl]guanidine (NIPMG) and 1,3-dimethyl-5-[(carbamimidamidomethanimidoil) amino]benzoyl-1,3dicarboxylate (DCB) on the degree of proteins oxidative modification (POM) and the DNA fragmentation, the content of the lipid peroxidation primary products - conjugated dienes (CD), and the activity of glutathione antioxidant system in the liver and heart of rats with experimental hyperglycemia was investigated. Administration of the biguanides (15.0 mg/kg) to hypoglycemic rats promoted reduction of the free radical processes intensity in the studied tissues. Data about CD and POM level changes in hyperglycemic rats treated by NIPMG and DKB correlate with the results of DNA fragmentation degree evaluation. At the same time, the activity of antioxidant enzymes (glutathione peroxidase and glutathione reductase), and the reduced glutathione content in the liver and heart of rats changed toward control values. For metformin, which was used as a comparison drug, changes in the studied parameters in the same direction were also found. These results indicate the ability of the tested biguanide derivatives to exhibit a positive regulatory effect on free radical homeostasis, reducing the degree of oxidative stress at this pathology.

[Pulmonary larval paragonimiasis mimicking lung cancer]. / Legochnyi larval'nyi paragonimoz, imitiruiushchii rak legkogo.

Larval paragonimiasis is a parasitic disease caused by lung fluke larvae. Unlike the classic form of paragonimiasis, the larval form occurs with a large number of clinical manifestations. However, this fact only complicates the diagnosis of larval paragonimiasis, for the abundance of clinical manifestations results in the misdiagnosis of other diseases. Another feature of this form of paragonimiasis is the tendency to generalize and mimic the clinical presentation of malignant neoplasms. The performed diagnostic measures failed to give an accurate view of the nature of the disease, therefore diagnostic thoracoscopy was carried out and biopsy specimens were taken from the subpleural region of dissemination, followed by urgent histologic examination suggestive of glandular cancer. This circumstance became the reason for atypical resection of the affected portion, which was done; however, the patient died from pulmonary thromboembolism on postoperative day 2. The main diagnosis of chronic pulmonary generalized paragonimiasis (cystic and pneumosclerotic phases) with neoplastic syndrome was posthumously made.

[Intensity of apoptotic processes, aconitate hydratase activity and citrate level in patients with type 2 diabetes mellitus complicated steatohepatitis under application of epifamin at basic therapy].

DNA fragmentation, caspase-1 and caspase-3, aconitate hydratase (AH) activities, and citrate content have been investigated in the blood of patients with type 2 diabetes mellitus complicated by steatohepatitis. These indicators of apoptotic processes intensity and oxidative stress development were estimated after basic treatment and a combined therapy including epifamin. Before treatment DNA fragmentation blood leukocytes, decrease of AH activity and increase of caspases activities in the serum of patients were detected. Treatment with epifamin provided more pronounced changes in the investigated parameters towards control values as compared to basis therapy. Epifamin caused a positive effect on the citrate content in the serum of patients. Epifamin inclusion to the basic therapy was accompanied by a more pronounced changes towards the normal values of such biochemical parameters as ALT, AST, b-lipoproteins, cholesterol, fasting glucose and postprandial glucose levels. All these changes may be obviously attributed to epifamin-induced correction of the melatonin level and manifestation of adaptogenic properties and antioxidant effects of the hormone.

[EFFECTS OF MELATONIN ON THE ACONITATE HYDRATASE ACTIVITY, CONTENT OF LIPID PEROXIDATION PRODUCTS AND SOME NON-ENZYMATIC ANTIOXIDANTS IN THE BLOOD OF PATIENTS WITH TYPE 2 DIABETES MELLITUS COMPLICATED BY STEATOHEPATITIS].

Type 2 diabetes mellitus complicated by steatohepatitis is accompanied by a decrease in aconitate hydratase activity, increase in the content of diene conjugates, decrease in the concentration of α-tocopherol, and change in the citrate level in the blood serum of patients, which is evidence of the development of oxidative stress as a result of the intensification of free radical oxidation of biosubstrates and decreasing degree of antioxidant defense of the organism. Combined therapy with melaxen provided a more significant change of the investigated parameters toward the norm (on the average by 36%, p 0.05) in comparison with basic treatment. This result was evidently associated with implementation of the antioxidant effect of melatonin, the level of which is corrected under the action of the drug employed.

[Effect of melaxen and valdoxan on free radical processes intensity, aconitate hydratase activity and citrate content in rats tissues under hyperthyroidism].

The influence of melaxen and valdoxan on the biochemiluminescence parameters, aconitate hydratase activity and citrate level in rats heart and liver during development of experimental hyperthyroidism has been investigated. Administration of these substances promoted a decrease of biochemiluminescence parameters, which had been increased in tissues of rats in response to the development of oxidative stress under hyperthyroidism. Aconitate hydratase activity and citrate concentration in rats liver and heart, growing at pathological conditions, changed towards control value after administration of the drugs correcting melatonin level. The results indicate the positive effect of valdoxan and melaxen on oxidative status of the organism under the development of experimental hyperthyroidism that is associated with antioxidant action of melatonin.