A Review of Depth and Normal Fusion Algorithms.

Geometric surface information such as depth maps and surface normals can be acquired by various methods such as stereo light fields, shape from shading and photometric stereo techniques. We compare several algorithms which deal with the combination of depth with surface normal information in order to reconstruct a refined depth map. The reasons for performance differences are examined from the perspective of alternative formulations of surface normals for depth reconstruction. We review and analyze methods in a systematic way. Based on our findings, we introduce a new generalized fusion method, which is formulated as a least squares problem and outperforms previous methods in the depth error domain by introducing a novel normal weighting that performs closer to the geodesic distance measure. Furthermore, a novel method is introduced based on Total Generalized Variation (TGV) which further outperforms previous approaches in terms of the geodesic normal distance error and maintains comparable quality in the depth error domain.

Effect of antioxidants on functional recovery after in vitro-induced ischemia and long-term potentiation recorded in the pyramidal layer of the CA1 area of rat hippocampus.

Ischemic stroke is one of the leading causes of cognitive impairment. Antioxidants may be beneficial in brain diseases in which oxidative stress can be assumed. The effect of two antioxidants, stobadine and its new derivative coded SMe1EC2, was studied on post-ischemic functional recovery in the hippocampus of young and 18-month-old rats. The synaptic transmission was apparently absent after 6-min hypoxia/hypoglycemia in both age groups. Re-oxygenation resulted in negligible functional recovery in untreated slices, yet the presence of pyridoindoles tested elicited improved recovery upon re-oxygenation. SMe1EC2 was found more effective in post-ischemic functional recovery and was further tested in the hippocampus of 15-month-old rats in long-term potentiation (LTP) experiments, a synaptic model of learning and memory mechanisms. In slices of aged rats, 3.5-min hypoxia/hypoglycemia resulted in depression of the LTP induction phase (immediately after high frequency stimulation) and this was prevented in the presence of SMe1EC2 (3 µmol/l). Upon "normoxia", marked amelioration of LTP was recorded in the presence of the antioxidant in about 1.5 order lower concentration. These results suggest a possible application of the pyridoindole in the management of brain ischemia and cognitive impairment.

Stobadine attenuates impairment of an intestinal barrier model caused by 4-hydroxynonenal.

Alterations in the intestinal barrier permeability occur in a broad spectrum of abdominally related pathologies, mostly due to disturbed oxidative homeostasis and increased lipid peroxidation. 4-Hydroxynonenal (HNE), a major lipid peroxidation product, is physiologically present in healthy gastric mucosa, but is increased in early stages of colon cancer and patients with duodenal peptic ulcer. Nevertheless, such supraphysiological levels of HNE have not yet been associated with increased intestinal permeability, even though, as we have described in this paper, they could play important role. In vitro model of intestinal barrier was established by growing Caco-2 cell line on cell culture permeable inserts. The pyridoindole derivative stobadine in hydrophilic and lipophilic form was used for barrier model protection. Both forms of stobadine were able to prevent damaging HNE effects, and reduce generation of reactive oxygen species and permeability of the intestinal barrier. Immunocytochemical analysis has confirmed beneficial effect of stobadine in reducing the formation of HNE-protein conjugates in the cells. Lipophilic form of stobadine proved to be more efficient than hydrophilic, implying importance of lipids in maintaining barrier function. The results obtained indicate that HNE might be important factor affecting intestinal barrier integrity, while stobadine could efficiently protect intestinal cells against harmful HNE effects.

Body distribution of C-methionine and FDG in rat measured by microPET.

Compounds (18)F-fluorodeoxyglucose ((18)FDG) and (11)C-methionine ((11)C-MET) are radiodiagnostics frequently used in clinical Positron Emission Tomography (PET) as well in preclinical studies of various pathologies. The present study was focused on the comparison of biodistribution of both radiotracers in intact Wistar rats. The animals were scanned by microPET twice. The first scanning was done after (11)C-MET administration, the second scan followed 5-7 days later using (18)FDG. The radiotracers were injected into the tail vein of animals in isoflurane anesthesia. After a redistribution period, whole body scans were obtained using eXplore Vista SrT GE tomograph. Accumulation of the drugs in tissues was expressed in relative values (% ID/g) in selected regions of interest. As arbitrary reference tissue for drug accumulation, the sternoclavicular area was used. (18)C-MET was found remarkably cumulating especially in the liver, spleen and distal part of the gastrointestinal tract. The compound was accumulated in the liver 6.9±0.92 (mean±SEM) times more intensively than in the reference tissue. The respective value for spleen and cecum/colon was 5.62±0.81 and 3.56±0.14 times. Accumulation of (11)C-MET in other body parts including the brain and heart was very low and was apparently equal to the arbitrary tissue (0.13±0.01% ID/g). In the same animals (18)FDG (biontFDG) was remarkably cumulated especially in Harderian glands compared to arbitrary tissue background (11.02±1.00 times), heart (7.52±1.70 times), brain (6.14±0.37 times), and colon (5.68±0.31 times). (18)FDG accumulation in the liver, spleen and other organs was apparently not different from that found in the background (0.14±0.02% ID/g). The data obtained may serve as reference values in further microPET preclinical studies with (11)C-MET and (18)FDG under the given conditions.

The new pyridoindole antioxidant SMe1EC2 and its intervention in hypoxia/hypoglycemia-induced impairment of longterm potentiation in rat hippocampus.

Previously, the pyridoindole SMe1EC2 was proved to inhibit lipoperoxidation and carbonylation of proteins in rat brain cortex in the system Fe(2+)/ascorbate and improvement of resistance of the rat hippocampus was reported against ischemic conditions in vitro (hypoxia/hypoglycemia) expressed by the enhanced neuronal response recovery in reoxygenation. The hippocampus fulfils many of the criteria for a neuronal correlate of learning and memory. Recently, an impairment of hippocampal long-term potentiation (LTP) was reported under oxidative stress. Different therapies, including antioxidants, have been studied intensively concerning the impairment of neuronal plasticity. In this study marked reduction of LTP, elicited by a single burst (100 Hz, 1s) in the CA3-CA1 area of rat hippocampal slices, was shown due to transient hypoxia/hypoglycemia compared to control slices. On the basis of previously reported antioxidant and neuroprotective effects of SMe1EC2, its effect on loss of LTP in the hippocampus due to ischemic conditions was studied in vitro. The pyridoindole tested improved hypoxia/hypoglycemia-induced reduction of LTP compared to untreated hypoxic slices. An opposite effect of SMe1EC2 on LTP induction was found in control slices. The mechanism of SMe1EC2 action on LTP in ischemic conditions has been suggested to differ from the mechanism of its effect in "normoxia" and may be due to different redox status in control and ischemic brain tissue. The manifested LTP-protective effect of SMe1EC2 observed in the rat hippocampus exposed to ischemia in vitro may find exploitation in therapy associated with injured neuronal plasticity in some conditions, including ischemia, trauma and aging in man.

Maternal treatment of rats with the new pyridoindole antioxidant during pregnacy and lactation resulting in improved offspring hippocampal resistance to ischemia in vitro.

OBJECTIVE: Damage to the developing brain may be caused by maternal environment, nutritional deficiencies, failure of protective mechanisms, etc. Further, the developing brain may be damaged by intrauterine ischemia or by ischemia in newborns complicated by perinatal asphyxia. There is an effort to find agents with neuroprotective effect on the developing brain. The aim was to study the effect of the new pyridoindole antioxidant SMe1EC2 on the resistance of offspring hippocampus exposed to ischemia in vitro after treatment of mothers. MATERIALS AND METHODS: The electrically evoked responses were determined by extracellular recording from offspring hippocampal slices. The effect of oral treatment of rats with SMe1EC2 over 18 consecutive days, from day 15 of gestation to day 10 post partum (PP) was analyzed in the model of ischemia in vitro measured on the hippocampus of 21-day-old pups, with focus on neuronal function recovery in reoxygenation. RESULTS: Increased recovery of neuronal response was found at the end of 20-min reoxygenation in offspring hippocampal slices exposed to 10-min hypoxia/hypoglycemia from rats whose mothers were treated with the dose of 50 and 250 mg/kg of SMe1EC2, compared to control offspring slices (mothers received vehicle over the same time). CONCLUSIONS: The increased offspring hippocampus resistance to hypoxia/hypoglycemia due to 18-day maternal treatment with SMe1EC2 might have been obtained via the transplacental way as well as in the neonatal period via breast milk, skin and saliva. The manifested neuroprotective effect of SMe1EC2 on the developing brain might find exploitation during risk pregnancy and delivery.

Neuropathy in a rat model of mild diabetes induced by multiple low doses of streptozotocin: effects of the antioxidant stobadine in comparison with a high-dose alpha-lipoic acid treatment.

Hyperglycaemia-induced oxidative stress makes an important contribution to the aetiology of diabetic neuropathy. The aim of our study was to evaluate the effect of the antioxidant stobadine (STB) in comparison with a treatment by a high-dose of alpha-lipoic acid (ALA), on the neurological consequences of chronic hyperglycaemia in an animal model of diabetes in Wistar rats (16 weeks old), made diabetic by streptozotocin (STZ 3 x 20 mg i.v.). Neuropathy was evaluated electrophysiologically by measuring motor nerve conduction velocity (NCV) in the 4th and 8th week in vivo and motor NCV and resistance to ischaemic conduction failure (RICF) of the sciatic nerve in the 10th week of the experiment in vitro. The therapy with ALA (100 mg/kg i.p., 5 times a week) and STB (25 mg/kg i.p., 5 times a week) had a significant effect on NCV in vivo in the 8th week of the experiment and no effect in the 10th week in vitro. The RICF elevated in diabetic animals was significantly modified by ALA. The effect of the antioxidant STB on NCV was comparable with that of ALA, while RICF was affected only by ALA. We conclude that treatment with appropriate antioxidants might partially prevent nerve dysfunction in diabetic rats.

Oxidative stress induced by the Fe/ascorbic acid system or model ischemia in vitro: effect of carvedilol and pyridoindole antioxidant SMe1EC2 in young and adult rat brain tissue.

New effective strategies and new highly effective neuroprotective agents are being searched for the therapy of human stroke and cerebral ischemia. The compound SMe1EC2 is a new derivative of stobadine, with enhanced antioxidant properties compared to the maternal drug. Carvedilol, a non-selective beta-blocker, possesses besides its cardioprotective and vasculoprotective properties also an antioxidant effect. We compared the effect of carvedilol and SMe1EC2, antioxidants with a similar chemical structure, in two experimental models of oxidative stress in young and adult rat brain tissue. SMe1EC2 was found to improve the resistance of hippocampal neurons to ischemia in vitro in young and even in 18-month-old rats and inhibited formation of protein carbonyl groups induced by the Fe(2+)/ascorbic acid pro-oxidative system in brain cortex homogenates of young rats. Carvedilol exerted a protective effect only in the hippocampus of 2-month-old rats and that at the concentration 10-times higher than did SMe1EC2. The inhibitory effect of carvedilol on protein carbonyl formation induced by the pro-oxidative system was not proved in the cortex of either young or adult rats. An increased baseline level of the content of protein carbonyl groups in the adult versus young rat brain cortex confirmed age-related changes in neuronal tissue and may be due to increased production of reactive oxygen species and low antioxidant defense mechanisms in the adult rat brain. The results revealed the new pyridoindole SMe1EC2 to be more effective than carvedilol in neuroprotection of rat brain tissue in both experimental models involving oxidative stress.

Effect of the new pyridoindole antioxidant SMe1EC2 on functional deficits and oedema formation in rat hippocampus exposed to ischaemia in vitro.

OBJECTIVES: The idea of neuroprotective therapy for ischaemic stroke is based on results from studies on experimental animal models of brain ischaemia demonstrating efficacy of many natural and synthetic agents. Contrary to positive conclusions with antioxidants from animal models, clinical experience failed to find neuroprotectants so efficient in human stroke, infarction, brain trauma, tissue preservation, etc. Thus new highly effective neuroprotective agents need to be discovered. METHODS: Effects of 10-day oral treatment with the new pyridoindole derivative, code SMe1EC2, was analysed in the model of ischaemia in vitro measured five days after oral treatment, with focus on neuronal function recovery. The responses were determined by extracellular recording from rat hippocampal slices. Further, effect of SMe1EC2, applied into the incubation medium before and during ischaemia in vitro, was studied on the oedema extent in neurons of the CA1 area. RESULTS: Ten-day oral treatment of rats with SMe1EC2 at the doses 50 or 250 mg/kg resulted in improved resistance of hippocampal neurons to 6.5-min hypoxia/hypoglycaemia in vitro measured during reoxygenation, compared to untreated rats. Application of the drug tested into the incubation medium 30 min before and during 6-min hypoxia/hypoglycaemia resulted in reduction of oedema formation in the CA1 area compared to untreated slices exposed to ischaemia in vitro. CONCLUSION: The current study confirmed the neuroprotective effect of the pyridoindole antioxidant SMe1EC2 on the level of recovery of neuronal function as well as on affection of morphological changes expressed by reduced oedema extent in the rat hippocampus under ischemic conditions in vitro.

Effect of transient ischemia on long-term potentiation of synaptic transmission in rat hippocampal slices.

OBJECTIVES: Long-term potentiation (LTP) of neuronal activity in the hippocampus is thought to be a substrate for learning and memory. The influence of ischemia (IS) (hypoxia/hypoglycemia) on induction of LTP of synaptic transmission (ST) by high frequency stimulation (HFS) was investigated in rat hippocampal slices. METHODS: Neurons were stimulated via Schäffer collaterals and field excitatory postsynaptic potentials (fEPSP) were recorded extracellularly from the CA1 region. LTP was induced by one single train (100 Hz, 1s). RESULTS: In controls LTP of ST after HFS was 179.70+/-12.53%. Short IS of 2.5-4.5 min elicited a transient failure of ST, with return to former value followed by further increase of fEPSP amplitude to 142.28+/-16.24%, compared to amplitude before IS. HFS was elicited 40 min after exposure to IS and LTP was measured over further 40-60 min. LTP in slices exposed to 2.5-4.5-min IS was 139.94+/-14.01%. IS of 6-7.5 min elicited a prolonged failure of ST, with almost full recovery (96.69+/-14.42%). LTP was not activated 40 min after 6-7.5-min IS and the amplitude of fEPSP was even reduced to 80.14+/-19.19% compared to the former mean value of fEPSP 10 min before HFS. CONCLUSION: The results revealed that prolonged 6-7.5-min IS influenced induction of LTP of ST in the hippocampus and thus it could have deleterious effects on learning and memory. These findings may have clinical implications in stroke, brain ischemia, sleep apnoe and call for studying the effect of neuroprotectants on the induction of LTP in hippocampus exposed to oxidative stress.

Effect of the pyridoindole SMe1EC2 and compounds affecting A(1) and A(2A) adenosine receptors in rat hippocampus under ischemia in vitro.

The effect of the newly synthesized pyridoindole antioxidant SMe1EC2 (1 micromol/l) and drugs activating or inhibiting adenosine receptors was tested under ischemia. Synaptic transmission was recorded extracellularly before and under 6-min ischemia and 20-min reoxygenation in rat hippocampal slices in vitro. In untreated slices, ischemia elicited failure of synaptic transmission and excitability expressed by a population spike decay (t(0.5) = 1.7 +/- 0.1 min) and poor recovery of synaptic transmission at the end of reoxygenation, expressed as percentage of PoS amplitude of that at zero minute of ischemia (9.9 +/- 3.6%). The compound SMe1EC2 increased recovery of PoS amplitude in reoxygenation (31.2 +/- 7.0% of that at the beginning of ischemia) and decreased the number of irreversibly damaged slices in reoxygenation (64%) compared to untreated slices (80%). Co-administration of SMe1EC2 + SCH-58261 (1 micromol/l, A(2A) adenosine receptor antagonist) resulted in delayed synaptic transmission decay during 6-min ischemia (t(0.5) = 2.3 +/- 0.1 min), increased PoS amplitude recovery during reoxygenation (37.7 +/- 12.4% of that at zero minute of ischemia), and in a decreased number of slices with damaged synaptic transmission at the end of reoxygenation (54%), all data compared to untreated controls. Co-administration of pyridoindole with CGS 21680 (1 micromol/l, A(2A) adenosine receptor agonist) or with DPCPX (100 nmol/l, A(1) adenosine receptor antagonist) eliminated the described effect. Further studies are required to elucidate the putative influence of manipulation with adenosine receptors on the neuroprotective effect of SMe1EC2 under ischemia.

Breath isoprene--aspects of normal physiology related to age, gender and cholesterol profile as determined in a proton transfer reaction mass spectrometry study.

BACKGROUND: This study was performed to clarify variations in breath isoprene concentrations with age, gender, body mass index (BMI) and total serum cholesterol. Our cohort consisted of 205 adult volunteers of different smoking background without health complaints. Total cholesterol in blood serum was measured in 79 of these volunteers. METHODS: Mixed expiratory exhaled breath was sampled using Tedlar bags. Concentrations of isoprene were then determined using proton transfer reaction-mass spectrometry. RESULTS: Isoprene concentrations ranged from 5.8 to 274.9 ppb, with an overall geometric mean (GM) of 99.3 ppb. There was no statistically significant difference in mean isoprene in breath between males and females (GM 105.4 and 95.5 ppb, respectively). Ageing led to a decrease in concentration in men, with an estimated slope of the regression line for log-transformed isoprene concentrations of -0.0049, but did not influence isoprene levels in women. We did not observe any significant correlation between isoprene breath content and cholesterol level in blood, even after adjusting for the possible influence of age. Similarly, no correlation was found between isoprene levels and BMI. CONCLUSIONS: Isoprene concentrations in exhaled breath showed gender-specific correlations with respect to age. Further investigations are necessary to clarify the relation between isoprene concentrations in exhaled breath and cholesterol levels and synthesis rates in blood.

Variability issues in determining the concentration of isoprene in human breath by PTR-MS.

This paper deals with variability issues connected with the proton transfer reaction-mass spectrometry (PTR-MS) measurements of isoprene concentration. We focus on isoprene as an abundant and widely studied compound in human breath. The variability caused by the measurement process is described by the within-sample distribution. Thus, based on the formula for computing isoprene concentration that reflects the principle of the PTR-MS, a theoretical model for the within-sample distribution of isoprene concentration is suggested. This model, which assumes that the distribution is proportional to a quotient of two independent Poisson-distributed random variables, is then confronted with empirical distributions obtained from 17 breath samples collected from a healthy individual within a month. (In each sample, isoprene concentration was determined 97 times.) The empirical within-sample distributions are also compared to normal and log-normal distributions. While those seem to be satisfactory approximations, the theoretical model is found suitable only in 10 out of 17 breath samples. We also comment on the stability of samples during the measurement process in the PTR-MS instrument and, for the sake of comparison, determine the within-sample and the within-subject variability of isoprene concentrations in our data. The respective geometric standard deviations are 1.01 and 1.29.

Acute toxicity of magnetic nanoparticles in mice.

OBJECTIVES: The acute toxicity of magnetic nanoparticles was effectively lowered by their encapsulation with poly(D,L lactide). In relation to the idea to use magnetic nanoparticles in development of new delivery systems suitable for targeted drug administration, the toxicological profile of five types of magnetic fluids was assessed in mice. METHODS: The nanoprecipitation method was used to prepare magnetic fluids containing nanoparticles of Fe(3)O(4) encapsulated with biodegradable substances. The acute toxicity testing was performed according to OECD Test Guideline 425. In the pilot distribution study a special staining method was examined for the detection of Fe ions in body tissues of mice after intravenous administration of magnetic fluids. RESULTS: The p.o. LD(50) values were greater than 2,000.0 mg/kg of body weight and i.v. LD(50) values were in the range of 231.7-558.9 mg/kg of body weight. CONCLUSIONS: Of the magnetic nanoparticles tested, those encapsulated with poly(D,L lactide) were the most prospective for further in vivo testing.

Content of protein carbonyl groups in gerbil brain after reversible bilateral carotid occlusion: effect of 2,3-dihydromelatonin.

OBJECTIVES: To investigate whether a new derivative of melatonin, (2,3-dihydromelatonin (DHM), prevented the oxidative stress induced by ischemia /reperfusion (I/R) in the gerbil brain. To specify the effect on endogenous antioxidant activity and protein modification in the brain cortex, we evaluated the contents of glutathione (total GSx=GSH+GSSG) and protein carbonyl groups (PCG). METHODS: Brain ischemia (I) was induced by (12 min) bilateral carotid occlusion (BCAO) in adult male gerbils (60-70 g b wt.) DHM (10 mg/kg) was administered i.p. 20 min before surgery, at the beginning of reperfusion (R), and then 2 and 6 hours later. Horizontal locomotor activity was recorded using the open-field test over the course of 24 hours. Contents of GSx and PCG were determined after 6h of reperfusion. Glutathione (GSx ) was determined spectrophotometrically using the microplate reader, lactate by the kit Randox, UK. The measurement of protein carbonyl (PCG) groups after their derivatization with 2,4-dinitrophenylhydrazine (DNPH) is the most widely used assessment of protein oxidation. The contents of PCG and malondialdehyde (MDA) were assayed spectrophotometrically. RESULTS: Evaluation of the data obtained from horizontal locomotor activity recorded over the course of 24 hours using the open-field test showed that hyperactivity induced by I/R was returned by DHM almost to its control value during the interval of up to 6 hours (from 18,000 to 5,000 cm distance traveled, p<0.05). I/R decreased the content of GSx by 27.2% (p<0.001). Administration of DHM resulted in maintaining the content of GSx at control values (p<0.05). DHM diminished the I/R-induced increase in PCG in the cortex by 34.2% (p<0.01). CONCLUSIONS: Our data indicate that the effect of DHM on the content of glutathione and protein carbonyl groups occurred during the first 6 hours of reperfusion. In this time interval both the content of GSx and protein carbonyl groups seem to be sensitive indicators of I/R-induced oxidative stress in the gerbil brain.

Effect of stobadine on leukocyte free radical generation in streptozotocin-diabetic rats: comparison with vitamin E.

We investigated a possible alteration in the ability of leukocytes to produce reactive oxygen species by stobadine, a pyridoindole antioxidant, in streptozotocin-diabetic rats. The production of free radicals from whole blood was assessed by luminol-enhanced chemiluminescence after stimulation by phorbol myristate acetate. The effects of vitamin E treatment were also evaluated and compared with the effects of combined treatment with stobadine. Diabetes was induced by streptozotocin (55 mg/kg i.p.). Some of diabetic rats and their age-matched controls were treated orally with a low dose of stobadine (24.7 mg/kg/day), vitamin E (400-500 IU/kg/day), or stobadine plus vitamin E for 10 weeks. Stobadine and vitamin E separately produced, to a similar degree, a reduction in diabetes-induced hyperglycemia. The phorbol myristate acetate stimulated chemiluminescence signal was markedly depressed in both moderate and severe diabetic rats. Stobadine treatment prevented this depression of the chemiluminescence response. Vitamin E treatment also eliminated the depression of the chemiluminescence signal in diabetic rats, and the combination with stobadine did not produce further improvement in leukocyte function. These results suggest that stobadine treatment alone is able to produce beneficial effects on leukocyte function and to maintain leukocyte free radical release during diabetes.

Pentose phosphate pathway, glutathione-dependent enzymes and antioxidant defense during oxidative stress in diabetic rodent brain and peripheral organs: effects of stobadine and vitamin E.

The aim of the present study was to investigate the effects of treatment with antioxidant stobadine (ST) on the activities of enzymes related with pentose phosphate pathway and glutathione-dependent metabolism and the other markers of oxidative stress in brain and peripheral organs of diabetic rats, and to compare the effects of ST treatment alone with the effects of treatments with another antioxidant vitamin E and ST plus vitamin E. Rats were made diabetic by the injection of streptozotocin (STZ; 55 mg/kg IP), and, 2 days later, some control and diabetic rats were left untreated or treated with ST (24.7 mg/kg/day, orally), vitamin E (400-500 U/kg/day, orally), or both substances together. In the brain, although 6-phosphogluconate dehydrogenase activity (6-PGD) did not change, glucose-6-phosphate dehydrogenase activity (G-6PD) was markedly increased in diabetic rats compared with controls; only combined treatment with ST and vitamin E produced a partial prevention on this alteration. The aorta G-6PD and 6-PGD of diabetic rats were 52% and 36% of control values, respectively. Neither single treatments with each antioxidant nor their combination altered the G-6PD and 6-PGD in aorta of diabetic rats. Glutathione peroxidase (GSHPx) activity was increased by STZ-diabetes in brain, heart, and kidney. In diabetic brain, vitamin E alone or combination with ST kept GSHPx at normal levels. Diabetes-induced stimulation in GSHPx did not decrease in response to the treatment with vitamin E in heart and kidney, but was greatly prevented by ST alone. The activity of glutathione reductase (GR) was decreased in brain and heart of diabetic rats. The treatment with each antioxidant or with a combination of both agents completely prevented this deficiency and resulted in further activation of GR in diabetic tissues. Glutathione S-transferase (GST) activity did not significantly change in diabetic brain and aorta. GST was stimulated by all treatment protocols in the brain of diabetic rats and was depressed in aorta of control rats. Catalase (CAT) was activated in diabetic heart but depressed in diabetic kidney. Diabetes-induced abnormalities in CAT activity did not respond to vitamin E alone in heart, was moderately ameliorated by the treatment with this vitamin in kidney, and was completely prevented by ST alone in both tissues. Superoxide dismutase (SOD) activity of brain and heart was unchanged by the diabetes but inhibited in diabetic kidney after the treatment ST alone or ST plus vitamin E. The lipid peroxidation (MDA) was increased in diabetic brain and heart. ST or vitamin E alone partly prevented diabetes-induced increase in MDA in brain and heart; however, antioxidant combination achieved a completely amelioration in MDA of these tissues of diabetic rats. Kidney MDA levels were similar in control and untreated diabetic animals. ST and vitamin E treatments, when applied separately or together, significantly reduced kidney MDA in both control and diabetic rats; and the combined effect of antioxidants was greater than that of each alone. These results are consistent with the degenerative role of hyperglycemia on cellular reducing equivalent homeostasis and antioxidant defense, and provide further evidence that pharmacological intervention of different antioxidants may have significant implications in the prevention of the prooxidant feature of diabetes and protects redox status of the cells.

In vivo treatment with stobadine prevents lipid peroxidation, protein glycation and calcium overload but does not ameliorate Ca2+ -ATPase activity in heart and liver of streptozotocin-diabetic rats: comparison with vitamin E.

Hyperglycemia leads to excess production of reactive oxygen species (ROS), lipid peroxidation and protein glycation that may impair cellular calcium homeostasis and results in calcium sequestration and dysfunction in diabetic tissues. Stobadine (ST) is a pyridoindole antioxidant has been postulated as a new cardio- and neuroprotectant. This study was undertaken to test the hypothesis that the treatment with ST inhibits calcium accumulation, reduces lipid peroxidation and protein glycation and can change Ca2+,Mg2+-ATPase activity in diabetic animals. The effects of vitamin E treatment were also evaluated and compared with the effects of combined treatment with ST. Diabetes was induced by streptozotocin (STZ, 55 mg/kg i.p.). Some of diabetic rats and their age-matched controls were treated orally with a low dose of ST (24.7 mg/kg/day), vitamin E (400-500 IU/kg/day) or ST plus vitamin E for 10 weeks. ST and vitamin E separately produced, in a similar degree, reduction in diabetes-induced hyperglycemia. Each antioxidant alone significantly lowered the levels of plasma lipid peroxidation, cardiac and hepatic protein glycation in diabetic rats but vitamin E treatment was found to be more effective than ST treatment alone. Diabetes-induced increase in plasma triacylglycerol levels was not significantly altered by vitamin E treatment but markedly reduced by ST alone. The treatment with each antioxidant completely prevented calcium accumulation in diabetic heart and liver. Microsomal Ca2+,Mg2+-ATPase activity significantly decreased in both tissues of untreated diabetic rats. ST alone significantly increased microsomal Ca2+,Mg2+-ATPase activity in the heart of normal rats. However, neither treatment with ST nor vitamin E alone, nor their combination did change cardiac Ca2+,Mg2+-ATPase activity in diabetic heart. In normal rats, neither antioxidant had a significant effect on hepatic Ca2+,Mg2+-ATPase activity. Hepatic Ca2+,Mg2+-ATPase activity of diabetic rats was not changed by single treatment with ST, while vitamin E alone completely prevented diabetes-induced inhibition in microsomal Ca2+,Mg2+-ATPase activity in liver. Combined treatment with ST and vitamin E provided more benefits in the reduction of hyperglycemia and lipid peroxidation in diabetic animals. This study describes potential mechanisms on cellular effects of ST in the presence of diabetes-induced hyperglycemia that may delay or inhibit the development of diabetic complications. The use of ST together with vitamin E can better control hyperglycemia-induced oxidative stress.