Oregano (Origanum vulgare) Essential Oil and Its Constituents Prevent Rat Kidney Tissue Injury and Inflammation Induced by a High Dose of L-Arginine.

This study aimed to evaluate the protective action of oregano (Origanum vulgare) essential oil and its monoterpene constituents (thymol and carvacrol) in L-arginine-induced kidney damage by studying inflammatory and tissue damage parameters. The determination of biochemical markers that reflect kidney function, i.e., serum levels of urea and creatinine, tissue levels of neutrophil-gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1), as well as a panel of oxidative-stress-related and inflammatory biomarkers, was performed. Furthermore, histopathological and immunohistochemical analyses of kidneys obtained from different experimental groups were conducted. Pre-treatment with the investigated compounds prevented an L-arginine-induced increase in serum and tissue kidney damage markers and, additionally, decreased the levels of inflammation-related parameters (TNF-α and nitric oxide concentrations and myeloperoxidase activity). Micromorphological kidney tissue changes correlate with the alterations observed in the biochemical parameters, as well as the expression of CD95 in tubule cells and CD68 in inflammatory infiltrate cells. The present results revealed that oregano essential oil, thymol, and carvacrol exert nephroprotective activity, which could be, to a great extent, associated with their anti-inflammatory, antiradical scavenging, and antiapoptotic action and, above all, due to their ability to lessen the disturbances arising from acute pancreatic damage. Further in-depth studies are needed in order to provide more detailed explanations of the observed activities.

Melatonin treatment prevents carbon-tetrachloride induced rat brain injury.

Introduction: Herein the neuroprotective properties of melatonin, a highly effective antioxidant, administered in a single dose 50 mg/kg intraperitoneally, were investigated in the brain tissue of Wistar rats acutely exposed to the toxin carbon-tetrachloride (1 mL/kg, intraperitoneally). Methods: To assess the degree of whole encephalic mass damage, biochemical parameters related to lipid and protein oxidation, antioxidant enzymes (catalase and superoxide dismutase), glutathione and inducible nitric oxide/arginase pathways were determined. Results: The results showed that carbon-tetrachloride impaired the function of antioxidant enzymes (reduced catalase and superoxide dismutase activities) and reduced glutathione-metabolizing enzymes (reduced glutathione, glutathione S-transferase and peroxidase activity). Furthermore, carbon-tetrachloride increased lipid peroxidation and protein oxidative damage in the brain tissue, as well as myeloperoxidase and inducible nitric oxide synthase content/activities. Conclusions: The application of a single dose of melatonin post intoxication has been able to reverse the disturbance in the function of antioxidant enzymes and alleviate the tissue damage caused by oxidative stress, indicating that melatonin could be a potential therapeutic agent in oxidative-damage related neurodegenerative disorders.

Melatonin as a Promising Anti-Inflammatory Agent in an In Vivo Animal Model of Sepsis-Induced Rat Liver Damage.

Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted. Our research demonstrated that treatment with MLT prevented an LPS-induced increase in pro-inflammatory cytokines TNF-α and IL-6 and NF-κB levels, and in the neutrophil to lymphocyte ratio (NLR). On the other hand, MLT prevented a decrease in the blood lymphocyte number induced by LPS administration. Also, treatment with MLT decreased the liver tissue expression of the CD14 molecule observed after sepsis induction. In summary, in rats with LPS-induced sepsis, MLT was shown to be a significant anti-inflammatory agent with the potential to change the liver's immunological marker expression, thus ameliorating liver function.

Acutely applied melatonin prevents CCl4-induced testicular lesions in rats: the involvement of the oxidative capacity and arginine metabolism

Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.

Lycopene and Caffeic Acid Phenethyl Ester Affect Caspase-3 Activity, but Do Not Alter the NO Pathway in Lung Tissue Damage Induced by Cisplatin.

INTRODUCTION: Antioxidants such as lycopene (LCP) and caffeic acid phenethyl ester (CAPE) represent ideal molecules for the treatment of different reactive oxygen species (ROS) associated disorders. Cisplatin is a chemotherapeutic agent, causing an increase in ROS and DNA damage, with numerous side effects, which include lung toxicity. In the presents study, we evaluated and mutually compared the potential of LCP and CAPE in preventing cisplatin-induced rat lung damage. METHODS: The study was done using pathohistological analysis and a panel of biochemical parameters that reflect lung oxidative tissue damage, inflammation, and apoptosis. RESULTS: The obtained results suggest that cisplatin (10 mg/kg) causes significant disturbances in the lung tissue morphology, followed by an increase in lipid peroxidization and protein modification. Also, a pronounced inflammatory response and cell apoptosis cascade activation was noted. Both LCP and CAPE were able to mitigate the changes, to a different extent, in oxidative damage and apoptosis progression induced by cisplatin. However, they both had limited effect on inflammation since they only prevented an increase in myeloperoxidase activity but had not been able to prevent the NO generation. CONCLUSION: It is hard to be exact in saying whether LCP or CAPE is better in preventing cis-platin-induced lung damage since they obviously possess different mechanisms of action.

Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride - involvement of oxidative damage, glutathione, and arginine and nitric oxide metabolism.

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg·kg-1), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative and oxidative capacities, nitric oxide and arginine metabolism, and the glutathione cycle. Additionally, the extrinsic apoptosis pathway related parameters were studied. Acute exposure to CCl4 led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, and carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase, and peroxidase) and glutathione-metabolizing (glutathione peroxidase, S-transferase, and reductase) enzymes. Furthermore, CCl4 caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content and activities and in two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a post-treatment prevented the changes induced by CCl4 to a differing extent, and in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue associated diseases.

The relationship between occupational stress, health status, and temporary and permanent work disability among security guards in Serbia.

Purpose. This study aimed to examine the influence of occupational stress on health status and work disability among security guards in Serbia. Methods. Three hundred and ninty nine male security guards (aged 25-65 years) were examined during regular medical preventive check-ups at the Institute of Occupational Health. Data on their health status and permanent and temporary work disability were obtained, and correlations with the levels of occupational stress (measured by occupational stress index [OSI] questionnaire) were analysed. Results. A high prevalence of health impairments, including diabetes (38.8%), dyslipidaemia (82.7%), hypertension (69.9%) and metabolic syndrome (77.7%), was found. Highly significant correlations were shown between reported levels of total stress at work (total OSI score) and measured values of glucose, lipids, blood pressure, heart rate, Framingham cardiovascular risk scale, occurrence of diabetes and impaired fasting glucose, dyslipidaemia, hypertension, metabolic syndrome, coronary heart disease, cerebrovascular insults, degenerative eye-fundus changes, and temporary and permanent work disability. All of these correlations remained significant even after adjustments for age, body mass index and smoking status. Regression analysis confirmed the independent effect of occupational stress on the analysed parameters. Conclusions. There is a significant independent impact of occupational stress on development of health impairments and work disability among security guards.

Xanthine Oxidase/Dehydrogenase Activity as a Source of Oxidative Stress in Prostate Cancer Tissue.

Prostate cancer (PC) is one of the most frequent malignancies. Better biomarkers are constantly wanted, such as those which can help with the prediction of cancer behavior. What is also needed is a marker which may serve as a possible therapeutic target. Oxidative stress (OS), which is a hallmark of cancer, is included in the pathogenesis and progression of PC. We have conducted the present study to determine whether xanthine oxidase/dehydrogenase activity is the source of OS in prostate tissue. We have also determined the concentration of TBA-reactive substances (TBARS) and advanced oxidation protein products (AOPP), as well as the activity of catalase. Xanthine oxidase (XO) activity is significantly higher (p < 0.001) in tumor tissue when compared to the control healthy tissue. The concentration of TBARS (p < 0.001) and AOPP (p < 0.05) are also higher in tumor tissue. Catalase has raised its activity (p < 0.05) versus the control. There is also a strong correlation between XO activity and prostate-specific antigen (PSA) levels in the serum. These results indicate a significant role of XO activity in OS in prostate carcinogenesis, and it could be a possible theranostic biomarker, which can be important for a better understanding of the disease, its evolution, and prognosis. A promising treatment may be using XO inhibitors such as allopurinol as adjuvant therapy.

Caffeic acid phenethyl ester attenuates changes in pancreatic tissue damage biomarkers induced by cisplatin.

Application of cisplatin (CP) for the treatment of different cancers is known to cause pancreatitis through an increase in reactive oxygen species production and promotion of inflammation. Caffeic acid phenethyl ester (CAPE), the main activity carrier of propolis extracts, was previously found to possess numerous beneficial properties. This study aims to determine for the first time the potential of CAPE in preventing CP-induced pancreatic tissue damage by studying the changes occurring on both biochemical and microscopic levels. The levels of serum α-amylase and a panel of pancreatic tissue biomarkers related to tissue injury (reduced glutathione, xanthine oxidase, malondialdehyde, and protein carbonylated concentration) and inflammation (myeloperoxidase, nitric oxide, and umor necrosis factor alpha) were studied in male Wistar rats treated with either CP alone or with CP and CAPE. Additionally, microscopic analysis of pancreatic tissue would be conducted as well. Application of CAPE together with CP statistically significantly prevented the disturbance in all here-studied pancreatic tissue damage and inflammation-related biomarkers. The changes in pancreas biochemical status was followed by morphological disturbance. The results of the present study suggest that CAPE could act as a protective agent in pancreatic damage that arises after CP application.

Anthocyanins Protect Hepatocytes against CCl4-Induced Acute Liver Injury in Rats by Inhibiting Pro-inflammatory mediators, Polyamine Catabolism, Lipocalin-2, and Excessive Proliferation of Kupffer Cells.

: This study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from Vaccinim myrtillus (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl4 (3 mL/kg, i.p.). The preventive treatment of the bilberry extract (200 mg anthocyanins/kg, orally, 7 days) prior to the exposure to the CCl4 resulted in an evident decrease in markers of liver damage (glutamate dehydrogenase, sorbitol dehydrogenase, malate dehydrogenase), and reduced pro-oxidative (conjugated dienes, lipid hydroperoxide, thiobarbituric acid reactive substances, advanced oxidation protein products, NADPH oxidase, hydrogen peroxide, oxidized glutathione), and pro-inflammatory markers (tumor necrosis factor-alpha, interleukin-6, nitrite, myeloperoxidase, inducible nitric oxide synthase, cyclooxygenase-2, CD68, lipocalin-2), and also caused a significant decrease in the dissipation of the liver antioxidative defence capacities (reduced glutathione, glutathione S-transferase, and quinone reductase) in comparison to the results detected in the animals treated with CCl4 exclusively. The administration of the anthocyanins prevented the arginine metabolism's diversion towards the citrulline, decreased the catabolism of polyamines (the activity of putrescine oxidase and spermine oxidase), and significantly reduced the excessive activation and hyperplasia of the Kupffer cells. There was also an absence of necrosis, in regard to the toxic effect of CCl4 alone. The hepatoprotective mechanisms of bilberry extract are based on the inhibition of pro-oxidative mediators, strong anti-inflammatory properties, inducing of hepatic phase II antioxidant enzymes (glutathione S-transferase, quinone reductase) and reduced glutathione, hypoplasia of Kupffer cells, and a decrease in the catabolism of polyamines.

Comparison between the effects of selenomethionine and S-adenosylmethionine in preventing cholestasis-induced rat liver damage.

We aimed to evaluate whether two methionine-related compounds, S-adenosylmethionine (SAM), and selenomethionine (SM), could lessen liver damage induced by regurgitated bile in a model of rat bile duct ligation (BDL). Hepatoprotective potentials of S-adenosylmethionine and selenomethionine were estimated based on the changes of serum liver damage parameters (aminotransferases, alkaline phosphatase, gamma-glutamyltranspeptidase and lactate dehydrogenase activity, and bilirubin concentration), tissue oxidative [xanthine oxidase (XO) and catalase activity, thiobarbituric acid reactive substances (TBARS) levels] and inflammatory [tumor necrosis factor-alfa (TNF-α) concentration] parameters, and morphological liver tissue alterations that follow cholestasis. The treatment regimens proved themselves able to prevent significant liver damage induced by cholestasis. Both SAM and SM decreased XO activity and TBARS levels and increased catalase activity, while only SM significantly reduced TNF-α concentration. Morphological changes related to bile-induced liver damage were also found to be partially diminished by SAM and SM. In view of the mechanisms of action of the two tested methionine-derived compounds, one might say that SM predominantly acted as an antioxidant, while SAM exerted its activity by potentially modulating different gene expression and protein structures. It is also worth mentioning that this is the first study (to the best of our knowledge) that dealt with the effects of SM on BDL-induced liver injury in rats and of the findings that speak favorably of this powerful antioxidant.

Development and design of novel cardiovascular therapeutics based on Rho kinase inhibition-In silico approach.

Rho kinases, one of the best-known members of the serine/threonine (Ser/Thr) protein kinase family, can be used as target enzymes for the treatment of many diseases such as cancer or multiple sclerosis, and especially for the treatment of cardiovascular diseases. This study presents QSAR modeling for a series of 41 chemical compounds as Rho kinase inhibitors based on the Monte Carlo method. QSAR models were developed for three random splits into the training and test set. Molecular descriptors used for QSAR modeling were based on the SMILES notation and local invariants of the molecular graph. The statistical quality of the developed model, including robustness and predictability, was tested with different statistical approaches and satisfying results were obtained. The best calculated QSAR model had the following statistical parameters: r2 = 0.8825 and q2 = 0.8626 for the training set and r2 = 0.9377 and q2 = 0.9124 for the test set. Novel statistical metric entitled as the index of ideality of correlation was used for the final model assessment, and the obtained results were 0.6631 for the training and 0.9683 for the test set. Molecular fragments responsible for the increases and decreases of the studied activity were defined and they were further used for the computer-aided design of new compounds as potential Rho kinase inhibitors. The final assessment of the developed QSAR model and designed inhibitors was achieved with the application of molecular docking. An excellent correlation between the results from QSAR and molecular docking studies was obtained.

Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes.

Hyperglycemia mediated oxidative stress and pro-angiogenic molecules such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9) are considered important for diabetic retinopathy onset and progression. Melatonin is a pineal hormone that regulates circadian and seasonal rhythms and most likely is involved in regulating glucose metabolism. We aimed to evaluate the potential benefit of melatonin supplementation to the pre-diabetic retina by assessing melatonin effects on lipid peroxidation (thiobarbituric acid reactive substances, TBARS), protein oxidation (advanced oxidation protein products, AOPP) and concentrations of inducible nitric oxide synthase (iNOS), VEGF and MMP9 in the retina of rats with pre-diabetes. Pre-diabetes was induced by streptozotocin (45 mg/kg, i.p.) following nicotinamide injection (110 mg/kg, i.p.). Beside mild hyperglycemia, lower serum insulin, increased fructosamine and lower HDL cholesterol, the present study demonstrated decreased serum melatonin in pre-diabetic rats, as well as, increased concentration of retinal TBARS, AOPP, iNOS, VEGF, and MMP9. Oral supplementation with melatonin (85 µg/animal/day) caused melatonin and HDL cholesterol levels to rise in treated rats and reduced levels of fasting serum glucose and fructosamine. It also affected serum insulin and quantitative insulin sensitivity check index (QUICKI) in treated groups but had no significant effect on non-fasting glucose. Finally, supplementation with melatonin reduced concentrations of TBARS, AOPP, iNOS, VEGF, and MMP9 in significant level, thereby exerting an overall positive effect on oxidative stress and pro-angiogenic signaling in the pre-diabetic retina. Thus, oral melatonin might be considered in an early treatment or in the prevention of retinal changes associated with pre-diabetes.

Comparison of recurrence patterns of colorectal cancer in laparoscopic and open surgery groups of patients: A meta-analysis.

PURPOSE: The purpose of this meta-analysis was to evaluate differences between laparoscopic and open surgery and also the development of local and distant colorectal cancer (CRC) recurrences in treated patients. METHODS: 2,058 cases treated with laparoscopic surgery and 2,365 cases with open surgery from 20 included studies were analyzed, using the random-effects model. The mean difference and odds ratio (OR) with 95% confidence interval (95%CI) were calculated. An overall and a subgroup analysis was performed according to the type of cancer - colon or rectal, and we registered the operating time, number of dissected lymph nodes and need for intraoperative blood transfusion in the laparoscopic and open surgery group of patients. RESULTS: The operating time in the laparoscopic surgery group was significantly longer than in the open surgery group (mean difference 38.23 min). There was no significant differences in the number of dissected lymph nodes between the two groups when we pooled data for treatment of CRC (p=0.16). The OR of overall and local recurrences was significantly decreased in patients in the laparoscopic surgery group compared to those in the open surgery group (OR 0.83; 95%CI 0.70-0.98; p=0.03) and (OR 0.70; 95%CI 0.50-0.97; p=0.03), respectively. No significant differences were found between patients who underwent laparoscopic surgery and those that had open surgery for distant recurrences after CRC treatment. CONCLUSIONS: There was statistically significant difference between laparoscopic or open surgery and development of local and overall CRC recurrences.

Preoperative Midregional Pro-Adrenomedullin and High-Sensitivity Troponin T Predict Perioperative Cardiovascular Events in Noncardiac Surgery.

OBJECTIVE: We evaluated the utility of preoperative midregional (MR) pro-adrenomedullin (proADM) and cardiac troponin T (TnT) for improved detection of patients at high risk for perioperative cardiac events and mortality after major noncardiac surgery. SUBJECTS AND METHODS: This prospective, single-center, observational study enrolled 79 patients undergoing major noncardiac surgery. After initial clinical assessment (clinical history, physical examination, echocardiogram, blood tests, and chest X-ray), MR-proADM and high-sensitivity TnT (hsTnT) were measured within 48 h prior to surgery by immunoluminometric and electrochemiluminescence immunoassay. Patients were followed by the consulting physician until discharge or up to 14 days in the hospital after surgery. Perioperative cardiac events included myocardial infarction and development or aggravation of congestive heart failure. Data were compared between patients who developed target events and event-free patients. RESULTS: Within 14 days of monitoring, 14 patients (17.72%) developed target events: 9 (11.39%) died and 5 (6.33%) developed cardiovascular events. The average age of the patients was 71.29 ± 6.62 years (range: 55-87). Sex, age, and hsTnT did not significantly differ between groups. MR- proADM concentration was higher in deceased patients (p = 0.01). The upper quartile of MR-proADM was associated with a fatal outcome (66.7 vs. 20.0%, p < 0.01) and with cardiovascular events (64.3 vs. 16.9%, p < 0.01). MR-proADM above the cutoff value (≥0.85) was associated with a fatal outcome (88.9 vs. 20.0%, p < 0.01) and cardiovascular events (71.4 vs. 28.6%, p < 0.01); this association was not observed for hsTnT. CONCLUSION: Preoperative measurement of MR-proADM provides useful information for perioperative cardiac events in high-risk patients scheduled for noncardiac surgery.

Influence of different wild-garlic (Allium ursinum) extracts on the gastrointestinal system: spasmolytic, antimicrobial and antioxidant properties.

OBJECTIVES: As there are no previous studies of the European wild-garlic (Allium ursinum) effects on the gastrointestinal system, despite its traditional applications in gastrointestinal disorders' treatment and regular use in the human diet, we have quantified and compared spasmolytic, antimicrobial and antioxidant activities of its different leaf extracts. METHODS: Wild-garlic extracts were tested for spasmolytic activity on isolated rat ileum, antimicrobial activity on selected Gram-positive and Gram-negative bacteria and fungi by microdilution method and antioxidant capacity by DPPH radical-scavenging assay. KEY FINDINGS: Wild-garlic extracts were found to decrease ileal basal tone. As the relaxation of K+ -induced contractions was similar to one caused by papaverin, the observed spasmolytic effect was most likely mediated through Ca2+ -channel inhibition. Ethanolic extract (with the highest phenolic and high alk(en)yl cysteine sulphoxides' levels) produced the strongest spasmolytic activity. In case of acetylcholine-induced contractions, only hydromethanolic extract showed no statistical difference in comparison with positive control. All samples exhibited certain antioxidant potential and strong antimicrobial activity against tested enteropathogenic strains (Salmonella enteritidis was the most sensitive, followed by Escherichia coli, Proteus mirabilis and Enterococcus faecalis). CONCLUSION: Besides other already established health-promoting effects, wild garlic could be useful in treatment of mild gastrointestinal disturbances.

Bilberry: Chemical Profiling, in Vitro and in Vivo Antioxidant Activity and Nephroprotective Effect against Gentamicin Toxicity in Rats.

We assessed possible protective effect of bilberry diet in rat model of nephrotoxicity. In vivo and in vitro antioxidant activity and chemical profiling of this functional food was performed. With aid of HPLC-DAD and spectrophotometric method, 15 individual anthocyanins were quantified alongside total tannin, phenylpropanoid, and anthocyanin content. The study was conducted on four groups of rats: control, treated with only gentamicin, treated with only bilberry, and treated with both gentamicin and bilberry. Kidney function was evaluated by tracking urea and creatinine. Morphology of renal tissue and its changes were recorded pathohistologically and quantified morphometrically. Bilberry (100 mg/kg daily) showed strong nephroprotective effect against gentamicin toxicity in rats (as shown through MDA, AOPP, and catalase levels). In conclusion, the demonstrated protective activity of bilberry extract matched well with the assessed in vivo and in vitro antioxidant activity as well as with its polyphenolic content, particularly with high anthocyanin levels. Copyright © 2016 John Wiley & Sons, Ltd.

The Effects of Melatonin on Oxidative Stress Parameters and DNA Fragmentation in Testicular Tissue of Rats Exposed to Microwave Radiation.

BACKGROUND: Microwaves from mobile phones are one of the environmental toxicants that are capable of compromising male fertility by inducing oxidative stress and apoptosis in the testes. Melatonin is a lipophilic tryptophan indole amine and a potent antioxidant. OBJECTIVES: The aim of the study was to evaluate the effect of melatonin treatment on oxidative stress parameters and DNA fragmentation in the testicular tissue of rats exposed to microwave radiation (4 h/day). MATERIAL AND METHODS: Adult Wistar rats were divided in 4 groups: I--treated with saline; II--treated with melatonin; III--exposed to microwaves; IV--exposed to microwaves and treated with melatonin. The melatonin (2 mg/kg ip) was administered daily. The animals were sacrificed after 20, 40 and 60 days. RESULTS: Melatonin treatment prevented previously registered increases in malondialdehyde after only 20 days. Furthermore, it reversed the effects of microwave exposure on xanthine oxidase (after 40 days) and acid-DNase activity (after 20 days). However, neither protein carbonyl content nor catalase and alkaline Dnase activity were changed due to melatonin treatment. CONCLUSIONS: Melatonin exerts potent antioxidant effects in the testes of rats exposed to microwaves by decreasing the intensity of oxidative stress; it also reduces DNA fragmentation.

Gene polymorphisms of tumor necrosis factor alpha and antioxidant enzymes in bronchial asthma.

BACKGROUND: Bronchial asthma is an inflammatory disease resulting from a combination of genetic and environmental factors. Single nucleotide polymorphisms in the regulatory regions of cytokine and antioxidant enzyme genes may affect cytokine production and enzyme activity, and thus play a contributory role in asthma pathogenesis. OBJECTIVES: The aim of this study was to examine the association of manganese superoxide dismutase (MnSOD) Ala16Val, catalase (CAT) A-21T and tumor necrosis factor alpha (TNF-α) G-308A polymorphisms with bronchial asthma. MATERIAL AND METHODS: A total of 79 patients with asthma and 95 healthy controls were screened for MnSOD Ala16Val, CAT A-21T and TNF-α G-308A polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The results obtained showed significantly higher prevalence of the MnSOD ValVal genotype (χ2=14.463, df=2, p=0.001) and MnSOD 16Val allele (χ2=12.862, p=0.026, OR=0.451, 95% CI=0.291-0.699) in patients with asthma compared to controls. The genotype and allele frequencies distribution of CAT A-21T and TNF-α G-308A gene polymorphisms did not show differences between patients and controls. CONCLUSIONS: Our results show an association of MnSOD Ala16Val genetic polymorphism with asthma in a Serbian population and suggest a protective role of the MnSOD 16Ala allele.

Short communication: Effect of commercial or depurinized milk diet on plasma advanced oxidation protein products, cardiovascular markers, and bone marrow CD34+ stem cell potential in rat experimental hyperuricemia.

Cardiovascular repair and myocardial contractility may be improved by migration of bone marrow stem cells (BMSC) and their delivery to the site of injury, a process known as BMSC homing. The aim of our study was to examine the dietary effect of a newly patented depurinized milk (DP) that is almost free of uric acid and purine and pyrimidine compounds compared with a standard commercial 1.5% fat UHT milk diet or allopurinol therapy in rat experimental hyperuricemia. Bone marrow stem cell potential (BMCD34(+), CD34-postive bone marrow cells), plasma oxidative stress parameters [advanced oxidation protein products, AOPP) and thiobarbituric acid reactive substances (TBARS)], myocardial damage markers [creatine phosphokinase (CPK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)], plasma cholesterol, and high-density lipoprotein cholesterol were investigated. The DP milk diet significantly increased the number of BMCD34(+) stem cells compared with commercial UHT milk. Allopurinol given alone also increased the number of BMCD34(+). Hyperuricemia caused a significant increase in all plasma enzyme markers for myocardial damage (CPK, LDH, and AST). A cardioprotective effect was achieved with allopurinol but almost equally with DP milk and more than with commercial milk. Regarding plasma AOPP, TBARS, and cholesterol levels, the most effective treatment was DP milk. In conclusion, the protective role of a milk diet on cardiovascular function may be enhanced through the new depurinized milk diet, which may improve cardiovascular system function via increased bone marrow stem cell regenerative potential, decreased plasma oxidative stress parameters, and decreased levels of myocardial damage markers and cholesterol. New dairy technology strategies focused on eliminating harmful milk compounds should be completely nontoxic. Novel milk products should be tested for their ability to improve tissue repair and function.