The effect of simvastatin in pancreas of diabetic rats

Growing evidences suggest that statins exert several cholesterol-independent pleiotropic effects in diabetes, but there is no consensus whether they are positive or negative. To shed more light on this issue, we examined the effect of simvastatin on β-cell regeneration in a diabetic state. Diabetes was induced in male Mill Hill rats with a single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were additionally separated into two subgroups: treated with simvastatin (5 mg/kg/day, i.g., 12 days) and control. Treatment of diabetic animals started after diabetes induction (glucose level ≥ 12 mmol/L). Our findings revealed that there is no increase in the area of insulin-immunopositive cells neither normalization of serum insulin level after simvastatin treatment of diabetic animals, although simvastatin increased nuclear immunopositivity for pancreas duodenum homeobox-1 (PDX-1) and proliferating cell nuclear antigen (PCNA). The data from this study suggest that 12-day treatment with simvastatin did not improve diabetes- induced disturbances in β-cell mass/function

Relation of Redox and Structural Alterations of Rat Skin in the Function of Chronological Aging

Accumulation of oxidative insults on molecular and supramolecular levels could compromise renewal potency and architecture in the aging skin. To examine and compare morphological and ultrastructural changes with redox alterations during chronological skin aging, activities of antioxidant defense (AD) enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), thioredoxin reductase (TR), and methionine sulfoxide reductase A (MsrA), and the markers of oxidative damage of biomolecules—4-hydroxynonenal (HNE) and 8-oxoguanine (8-oxoG)—were examined in the rat skin during life (from 3 days to 21 months). As compared to adult 3-month-old skin, higher activities of CAT, GSH-Px, and GR and a decline in expression of MsrA are found in 21-month-old skin. These changes correspond to degenerative changes at structural and ultrastructural levels in epidermal and dermal compartments, low proliferation capacity, and higher levels of HNE-modified protein aldehydes (particularly in basal lamina) and 8-oxoG positivity in nuclei and mitochondria in the sebaceous glands and root sheath. In 3-day-old skin, higher activities of AD enzymes (SOD, CAT, GR, and TR) and MsrA expression correspond to intensive postnatal development and proliferation. In contrast to 21-month-old skin, a high level of HNE in young skin is not accompanied by 8-oxoG positivity or any morphological disturbances. Observed results indicate that increased activity of AD enzymes in elderly rat skin represents the compensatory response to accumulated oxidative damage of DNA and proteins, accompanied by attenuated repair and proliferative capacity, but in young rats the redox changes are necessary and inherent with processes which occur during postnatal skin development. Мorphological and ultrastructurаl changes are in line with the redox profile in the skin of young and old rats

Impact of nutrition on human fertility

Infertility is one of the most serious medical issues that is dramatically rising worldwide. Extensive research dedicated to this problem clearly shows that infertility is a disease of modern society and that a nutrition has a great infl uence on the development of sterility. Thus, the impact of specifi c nutritional factors, i.e. diet pattern on both male and female fertility is included in this review. It is encouraging that modifi cation of nutritional habits can help couples to conceive spontaneously, or increase their chances of conception with in vitro fertilization (IVF) treatment

Fractal and stereological analyses of insulin-induced rat exocrine pancreas remodelling

Background: The effect of insulin on the endocrine pancreas has been the subject of extensive study, but quantitative morphometric investigations of the exocrine pancreas are scarce. This study was therefore undertaken to investigate the effect of acute and chronic insulin administration (two doses, 0.4 IU and 4 IU) on the morphology of rat pancreas acini. Materials and methods: Semi-fine sections stained with methylene blue and basic fuchsine or haematoxylin and eosin-stained 5-micrometer thick paraffin sections were used for fractal and stereological analysis of exocrine acini. Acute insulin treatment, independent of applied doses increased fractal dimension in line with decreased lacunarity of pancreas acini. Chronic low dose insulin decreased fractal dimension and increased lacunarity of pancreas acini, but a high dose had the opposite effect. The volume densities (Vv) of cytoplasm, granules and nucleus are affected differently: acute low dose and high chronic dose significantly decreased granules Vv, and in line increased cytoplasmic Vv, whereas other examined structures showed slight changes without statistical significance. Results: The results obtained from this investigation indicate that insulin treatment induced structural remodelling of the exocrine pancreas suggesting a substantial role of insulin in its functioning. Conclusions: Additionally, we showed that fine architectural changes in acini could be detected by fractal analysis, suggesting this method as an alternative or addition to routine stereology

Health Benefits of Fasting and Caloric Restriction

Purpose of Review: Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes. Recent Findings: Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. Summary: There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.Current Diabetes Reports (2017), 17(12): 12

Development of an Analytical Assay for Electrochemical Detection and Quantification of Protein-Bound 3-Nitrotyrosine in Biological Samples and Comparison with Classical, Antibody-Based Methods.

Reactive oxygen and nitrogen species (RONS) cause oxidative damage, which is associated with endothelial dysfunction and cardiovascular disease, but may also contribute to redox signaling. Therefore, their precise detection is important for the evaluation of disease mechanisms. Here, we compared three different methods for the detection of 3-nitrotyrosine (3-NT), a marker of nitro-oxidative stress, in biological samples. Nitrated proteins were generated by incubation with peroxynitrite or 3-morpholino sydnonimine (Sin-1) and subjected to total hydrolysis using pronase, a mixture of different proteases. The 3-NT was then separated by high performance liquid chromatography (HPLC) and quantified by electrochemical detection (ECD, CoulArray) and compared to classical methods, namely enzyme-linked immunosorbent assay (ELISA) and dot blot analysis using specific 3-NT antibodies. Calibration curves for authentic 3-NT (detection limit 10 nM) and a concentration-response pattern for 3-NT obtained from digested nitrated bovine serum albumin (BSA) were highly linear over a wide 3-NT concentration range. Also, ex vivo nitration of protein from heart, isolated mitochondria, and serum/plasma could be quantified using the HPLC/ECD method and was confirmed by LC-MS/MS. Of note, nitro-oxidative damage of mitochondria results in increased superoxide (O2•-) formation rates (measured by dihydroethidium-based HPLC assay), pointing to a self-amplification mechanism of oxidative stress. Based on our ex vivo data, the CoulArray quantification method for 3-NT seems to have some advantages regarding sensitivity and selectivity. Establishing a reliable automated HPLC assay for the routine quantification of 3-NT in biological samples of cell culture, of animal and human origin seems to be more sophisticated than expected

Antioxidative defense and mitochondrial thermogenic response in brown adipose tissue

Cold-exposure activates interscapular brown adipose tissue (IBAT) non-shivering thermogenesis that relies primarily on intensification of metabolic rate and uncoupling. During cold-acclimation, uncoupling in IBAT decreases superoxide (O2·−) production and as an adaptive response the activities of manganese and copper, zinc superoxide dismutase (Mn- and CuZn-SOD, respectively) are decreased, as well. However, molecular mechanisms governing this SODs adaptive response are still unsolved. Besides, knowing that NO reinforces IBAT uncoupling, we wondered whether nitric oxide (NO) is taking part in SODs regulation? Mn- and CuZn-SOD mRNA and protein expression, uncoupling protein 1 (UCP1), nitrotyrosine and nuclear factor-kappa B (NF-κB) immunolabeling, as well as total SOD (tSOD) activity in IBAT of rats subjected to cold (4 ± 1°C) for 1, 3, 7, 12, 21 and 45 days and treated by l-arginine or Nω-nitro-l-arginine-methyl ester (l-NAME) were examined. Cold increased UCP1 immunopositivity and decreased tSOD activity during entire cold-acclimation and transiently, (day 3), activated NF-κB and increased Mn and CuZn-SOD mRNA expression and nitrotyrosine labeling, suggesting NO involvement in this signaling. However, SODs mRNA expression was decreasing from day 12 till the end of cold-acclimation. l-arginine augmented and prolonged cold-induced UCP1 and nitrotyrosine immunopositivity, NF-κB activation and SODs mRNA expression increase, while l-NAME expressed an opposite effect. Related to cold, l-arginine decreased, while l-NAME increased Mn-SOD protein expression. In contrast, neither low temperature nor both treatments applied affected CuZn-SOD protein expression. The results showed that adaptive decrease in SODs activity on uncoupling-decreased O2·− production was achieved already at the level of gene transcription and that NO takes part in the regulation of IBAT SOD isoforms

Doxorubicin toxicity to the skin: possibility of protection with antioxidants enriched yeast

The possibility of skill protection against doxorubicin toxicity was examined after oral antioxidative pretreatment of the rats with yeast supplemented with selenium and vitamins E, C and A for 15 days. The activity and level of antioxidative defense components were monitored in the skin and blood 48 h after i.v. applied dosorubicin. In the blood, increased glutathione peroxidase activity in the erythrocytes, and amounts of vitamin E and glutathione in the plasma were found after the antioxidative treatment. It also led to an increase of the reductive capacity in the skin (increased thioredoxin reductase activity and reduced glutathione level). Doxorubicin alone, depleted reductive capacity, i.e. decreased the activity of thioredoxin reductase in the skin, as well as the content of reduced glutathione both in the skin and blood plasma. Depletion of reductive capacity represents one of the first harmful doxorubicin effects to the skin at the time when the changes of other antioxidative enzyme activities were not detectable. Reductive capacity in the skin of animals given antioxidative pretreatment was maintained elevated upon doxorubicin application in comparison with the corresponding control. Oral supplementation with antioxidants thus prevents toxic effects of doxorubicin in the skill and may contribute to the alleviation of its secondary cytotoxicity during the chemotherapy. (C) 2001 Elseviecr Science Ireland Ltd. All rights reserved.nul

Doxorubicin toxicity to the skin: possibility of protection with antioxidants enriched yeast

The possibility of skill protection against doxorubicin toxicity was examined after oral antioxidative pretreatment of the rats with yeast supplemented with selenium and vitamins E, C and A for 15 days. The activity and level of antioxidative defense components were monitored in the skin and blood 48 h after i.v. applied dosorubicin. In the blood, increased glutathione peroxidase activity in the erythrocytes, and amounts of vitamin E and glutathione in the plasma were found after the antioxidative treatment. It also led to an increase of the reductive capacity in the skin (increased thioredoxin reductase activity and reduced glutathione level). Doxorubicin alone, depleted reductive capacity, i.e. decreased the activity of thioredoxin reductase in the skin, as well as the content of reduced glutathione both in the skin and blood plasma. Depletion of reductive capacity represents one of the first harmful doxorubicin effects to the skin at the time when the changes of other antioxidative enzyme activities were not detectable. Reductive capacity in the skin of animals given antioxidative pretreatment was maintained elevated upon doxorubicin application in comparison with the corresponding control. Oral supplementation with antioxidants thus prevents toxic effects of doxorubicin in the skill and may contribute to the alleviation of its secondary cytotoxicity during the chemotherapy. (C) 2001 Elseviecr Science Ireland Ltd. All rights reserved.nul

Antioxidative defense in the rat skin after the adaptation to cold

(1) Activity of superoxide dismutase (CuZn- and Mn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione S-transferase (GST) and thioredoxin reductase (TR), and the amount of glutathione (GSH) were assayed in the skin of control (22 +/- 1degreesC), cold-adapted rats (45 days, 5 +/- 1degreesC), and cold-adapted rats brought back to room temperature after 1, 3, 7 and 15 days. (2) There were no changes in the observed components of the antioxidative defense in the skin of the cold-adapted rats. (3) During the re-adaptation of cold-adapted rats (18.8 +/- 3.1 nM GSH g(-1) tissue), only changes in the skin GSH level were found. After 1, 3 and 7 days of re-adaptation (39.5+/-5.3, 51.5+/-4.93 and 51.2+/-8.35 nM GSH g(-1) tissue, respectively) the amount of GSH was considerably increased, while after 15 days at room temperature (19.1+/-2.3 nM GSH g(-1) tissue) it declined to control levels (20.7+/-3.1 nM GSH g(-1) tissue). (C) 2003 Elsevier Science Ltd. All rights reserved.nul