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.

The role of melatonin in preventing amiodarone-induced rat liver damage.

Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50 mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70 mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose.

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.

In silico approach for the development of novel antiviral compounds based on SARS-COV-2 protease inhibition.

The COVID-19 pandemic emerged in 2019, bringing with it the need for greater stores of effective antiviral drugs. This paper deals with the conformation-independent, QSAR model, developed by employing the Monte Carlo optimization method, as well as molecular graphs and the SMILES notation-based descriptors for the purpose of modeling the SARS-CoV-3CLpro enzyme inhibition. The main purpose was developing a reproducible model involving easy interpretation, utilized for a quick prediction of the inhibitory activity of SAR-CoV-3CLpro. The following statistical parameters were present in the best-developed QSAR model: (training set) R 2 = 0.9314, Q 2 = 0.9271; (test set) R 2 = 0.9243, Q 2 = 0.8986. Molecular fragments, defined as SMILES notation descriptors, that have a positive and negative impact on 3CLpro inhibition were identified on the basis of the results obtained for structural indicators, and were applied to the computer-aided design of five new compounds with (4-methoxyphenyl)[2-(methylsulfanyl)-6,7-dihydro-1H-[1,4]dioxino[2,3-f]benzimidazol-1-yl]methanone as a template molecule. Molecular docking studies were used to examine the potential inhibition effect of designed molecules on SARS-CoV-3CLpro enzyme inhibition and obtained results have high correlation with the QSAR modeling results. In addition, the interactions between the designed molecules and amino acids from the 3CLpro active site were determined, and the energies they yield were calculated. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-022-02170-8.

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.

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.

Morphometric analysis of structural renal alterations and beneficial effects of aminoguanidine in acute kidney injury induced by cisplatin in rats.

Since cisplatin-induced nephrotoxicity has very important clinical consequences, the purpose of this study was to determine the potential protective effect of aminoguanidine on the acute kidney injury caused by cisplatin. Experiments were done on 40 Wistar rats divided into four groups. The CIS group received cisplatin in a single dose of 8 mg/kg, while the CISAG group received the same dose of cisplatin and aminoguanidine (100 mg/kg) by intraperitoneal injections. Animals in the AG group received only aminoguanidine (100 mg/kg) and those in the C group received saline. Quantitative evaluation of structural and functional alterations in the kidneys was performed by analysis of biochemical and parameters of oxidative stress and by histological and morphometric analysis of renal sections. Histological sections of kidney showed structural damage of proximal tubules and glomeruli that were induced by cisplatin. Morphometric analysis revealed statistically significant differences in the area of proximal tubules and the size and cellularity of glomeruli between the CIS and CISAG groups. Glomerular basement membrane thickness was increased in the CIS group, while aminoguanidine attenuated these changes in the CISAG group of rats. Our results suggest that aminoguanidine acts protectively and repairs structural and functional damage of kidney by engaging the existent antioxidative potential at the level of renal tissue.

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.

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.

Two different melatonin treatment regimens prevent an increase in kidney injury marker-1 induced by carbon tetrachloride in rat kidneys.

Acute kidney injury is a frequent disorder that can be mimicked by the application of different nephrotoxic agents, including carbon tetrachloride (CCl4), where kidney injury marker-1 (KIM-1) has been recognized as a highly specific marker. Melatonin is one of the most powerful natural antioxidants and has numerous beneficial properties. We evaluated the nephroprotective potential of 2 melatonin treatment regimens (pre- and post-intoxication) in a CCl4-induced acute kidney injury model based on the standard serum parameters, kidney tissue antioxidative capacity, KIM-1 levels, and kidney tissue morphological changes. The two treatment regimens were found to preserve kidney function, as judged from the evaluated standard serum parameters. Only when administered after the intoxication, melatonin preserved total kidney antioxidant capacity; pre-treatment melatonin only preserved reduced glutathione levels. An increase in tissue KIM-1 level was found to be prevented by both treatment regimens, which correlated with the morphological changes seen in the kidney tissues of animals treated with melatonin and CCl4. The findings of our study are in agreement with the known actions of melatonin in relieving kidney tissue oxidative burden, but also contribute to the understanding of its action by preventing an increase in KIM-1.

Exogenous putrescine affects polyamine and arginine metabolism in rat liver following bile ductus ligation.

Rat bile duct ligation (BDL) represents a useful method that mimics obstructive extrahepatic cholestasis, which is known to be a frequent disorder in humans. Polyamines (putrescine, spermidine, and spermine) are one of the key molecules regulating cell proliferation and differentiation. This work aimed to evaluate the potential beneficial properties of putrescine in rat BDL model by studying several biochemical parameters reflecting liver function and polyamine metabolism. Rats that were subjected to BDL were injected with putrescine (150 mg/kg) for 9 days, while in parallel another group with BDL remained untreated. Two control groups were included as well, sham-opened and putrescine-treated group. The following plasma parameters: ALT, AST, γ-GT, ALP, bilirubin, bile acids, as well as liver malondialdehyde and polyamine concentration and the activity of enzymes involved in polyamine metabolism were studied. After BDL, significant alterations in plasma biochemical parameters occurred, where a 9-day putrescine treatment significantly alleviated liver function deterioration. Putrescine also increased liver polyamines' concentrations and polyamine and diamine oxidase activities in rats submitted to BDL. Our results demonstrated, for the first time, that putrescine plays an important role in preserving liver tissue function in rats with experimentally induced cholestasis.

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.

Effects of melatonin on oxidative stress parameters and pathohistological changes in rat skeletal muscle tissue following carbon tetrachloride application.

Animal models demonstrating skeletal muscle (SM) disorders are rarely investigated, although these disorders accompany liver disorders and can occur during prolonged exercise/training. In cases of SM disorders exogenous antioxidants, such as melatonin, could help by generally improving tissues antioxidant capacities. We aimed to analyze the potential of melatonin in preventing biochemical and structural changes in rat biceps muscle (BM) occurring after an acute exposure to carbon tetrachloride (CCl4). Biceps muscles obtained from male Wistar rats belonging to different experimental groups were biochemically (determination of tissue MDA, total antioxidant capacity, GSH, CAT, SOD and GPx activities) and pathologically analyzed. Also, serum levels of potassium, LHD and CK were analyzed in all experimental animals. The obtained results were statically compared with those from vehicle-treated control group. The applied melatonin prevented potassium and intracellular enzyme leakage (CK and LDH) that was induced by CCl4, as well as an increase in tissue MDA. From a panel of determined oxidative stress parameters melatonin was able to statistically significantly prevent changes in total antioxidative capacity and in CAT, SOD and GPx activities induced by CCl4. Microscopic analysis of BM from the animals exposed to CCl4 revealed significant muscle fiber disorganization and massive inflammatory cell infiltration. All these changes were significantly ameliorated in the group that received melatonin prior to CCl4. Changes in serum and tissue biochemical parameters accompanied the observed pathological changes, which demonstrated a significant influence of melatonin in preventing skeletal muscle damage induced by CCl4.

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.

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.

Arginase activity and lecithin/sphingomyelin (l/s) ratio in the amniotic fluid of pregnant women.

Arginase activity is important in polyamines and nitric oxide production which are required for the normal growth of placenta and embryo. A considerable arginase activity is observed in amniotic fluid in women at the end of pregnancy. Lecithin to sphingomyelin (L/S) ratio is widely used in order to assess fetal lung immaturity and prevention of neonatal respiratory distress syndrome, the major cause of neonatal morbidity and mortality. The purpose of our study was to determine if there is a relationship between arginase activity and L/S ratio in amniotic fluid. The study included 170 pregnant women, 18-43 years old, with normal and pathological pregnancy. The arginase activity was measured on the basis of the determination of the amount of liberated ornithine from arginine as substrate. The L/S ratio was done by using a thin layer chromatography. Increased level of arginase activity correlates with the fetal lung maturity. Arginase activity and L/S values may be useful biochemical data, for intrauterine baby maturity.

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.

Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease.

Purine nucleotide liberation and their metabolic rate of interconversion may be important in the development of hypertension and its renal consequences. In the present study, blood triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) breakdown pathway was evaluated in relation to uric acid concentration and xanthine dehydrogenase/xanthine oxidase (XDH/XO) in patients with essential hypertension, patients with chronic renal diseases on dialysis, and control individuals. The pattern of nucleotide catabolism was significantly shifted toward catabolic compounds, including ADP, AMP, and uric acid in patients on dialysis program. A significant fall of ATP was more expressed in a group of patients on dialysis program, compared with the control value (p<0.001), while ADP and AMP were significantly increased in both groups of patients compared with control healthy individuals (p<0.001), together with their final degradation product, uric acid (p<0.001). The index of ATP/ADP and ATP/uric acid showed gradual significant fall in both the groups, compared with the control value (p<0.001), near five times in a group on dialysis. Total XOD was up-regulated significantly in a group with essential hypertension, more than in a group on dialysis. The activity of XO, which dominantly contributes reactive oxygen species (ROS) production, significantly increased in dialysis group, more than in a group with essential hypertension. In conclusion, the examination of the role of circulating purine nucleotides and uric acid in pathogenesis of hypertension and possible development of renal disease, together with XO role in ROS production, may help in modulating their liberation and ROS production in slowing progression from hypertension to renal failure.

The Influence of Removable Complete Denture on Pro-Oxidant Antioxidant Balance and Redox-Sensitive Inflammation Biomarker NF-ĸB in the Oral Cavity: An Interventional Follow-Up Study.

OBJECTIVES: Oxidative stress, an imbalance between the body's natural antioxidant defenses and the production of reactive oxygen species (ROS), can result in serious oral diseases, including oral cancer, periodontal diseases, and oral lichen planus, through the activation of the redox-sensitive transcription factors and inflammation. The purpose of this study was to assess the potential effects of a removable complete denture on the levels of oxidative stress markers, such as lipid peroxidation (MDA), advanced oxidation protein products (AOPP), and catalase, and the quantitative expression of the redox-sensitive transcription factor NF-κB p65 subunit. MATERIALS AND METHODS: This interventional follow-up study enrolled 40 participants of both sexes aged 28-78 years, with a median age of 56 years, where unstimulated saliva was collected before denture placement, immediately after the denture placement, and 24 h, 7 days, and 30 days after the denture placement. The most prominent ROS overproduction was reported on the seventh day (p < 0.05), followed by a significant fall in antioxidative defense. RESULTS: The NF-κB p65 subunit, whose expression pattern was highest in the same time period on the seventh day, serves as a signaling molecule for redox imbalance due to ROS production. Over the next 30 days, its levels remained moderately increased compared to the basal value, which may influence pro-inflammatory pathways and the integrity of oral tissue components. These alterations may be induced by the dentures, which can produce high pressures on the supporting tissues or by the synthetic materials used for producing the dentures. CONCLUSION: Our research may help to clarify the potential pathways by which oxidative stress and redox-sensitive inflammatory mediators, as well as mechanical and chemical irritants, may serve as risk factors for premalignant lesions in the mouth. Further research on this topic is required to understand the molecular mechanisms behind the relationship between inflammation and oral premalignant lesions caused by mechanical and chemical irritation.

Melatonin inhibits apoptosis and oxidative tissue damage in cisplatin-induced pulmonary toxicity in rats.

Introduction: Cisplatin is one of the most frequently used chemotherapeutics, which is known to cause both tumor and normal lung tissue damage through the generation of free radicals and cells apoptosis/necrosis. Melatonin is a neurohormone that regulates numerous physiological processes in the body both through receptor pathways and by maintaining tissue redox homeostasis. Material and methods: The extent of rat lung damage induced by cisplatin and the effects of melatonin on this process was determined based on the pathohistological changes and biochemical disturbances in tissue lipid peroxidation, protein carbonyl modification and in the activity of xanthine oxidase (XO), caspase-3 and DNases. Results: Histopathological analysis of rat lung tissue obtained from animals that received cisplatin found them to be edematous, with significant deterioration of alveolar epithelium. These morphological changes are accompanied by a significant increase in all studied oxidative stress-related parameters, as well as with the activity of apoptosis-related enzymes. A five-day treatment with melatonin completely prevented a cisplatin-induced increase in oxidative stress-related parameters and in the activity of XO, caspase-3 and alkaline DNase. Also, the histopathological changes observed during microscopic analysis were much less pronounced than in the group that received cisplatin only. Conclusions: These results can potentially be connected with the ability of melatonin to inhibit the activity of XO, caspase-3 and alkaline DNase and/or its ability to scavenge free radicals, thus preventing lung damage induced by cisplatin.