The Impact of the High-Fructose Corn Syrup on Cardiac Damage via SIRT1/PGC1-α Pathway: Potential Ameliorative Effect of Selenium.

High-fructose corn syrup (HFCS) has been a subject of intense debate due to its association with cardiovascular risks. This study investigates the potential protective effects of selenium (Se) supplementation against cardiac damage induced by HFCS. Thirty-two male Wistar albino rats were divided into four equal groups: control, CS (20%-HFCS), CS with Se (20%-HFCS, 0.3 mg/kg-Se), and Se (0.3 mg/kg-Se) only. After a 6-week period, heart and aorta tissues were collected for histopathological, immunohistochemical, biochemical, and genetic analyses. HFCS consumption led to severe cardiac pathologies, increased oxidative stress, and altered gene expressions associated with inflammation, apoptosis, and antioxidant defenses. In the CS group, pronounced oxidative stress within the cardiac tissue was concomitant with elevated Bcl-2-associated X protein (Bax) expression and diminished expressions of B-cell-lymphoma-2 (Bcl-2), nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), and silenced information regulator 1 (SIRT1). Se supplementation mitigated these effects, showing protective properties. Immunohistochemical analysis supported these findings, demonstrating decreased expressions of caspase-3, tumor necrosis factor-alpha (TNF-α), IL-1ß, and vascular endothelial growth factor (VEGF) in the CS + Se group compared to the CS group. The study suggests that Se supplementation exerts anti-inflammatory, antioxidant, and antiapoptotic effects, potentially attenuating HFCS-induced cardiovascular toxicity. These findings highlight the importance of dietary considerations and selenium supplementation in mitigating cardiovascular risks associated with HFCS consumption.

Irbesartan ameliorates inflammation via transendothelial leukocyte migration due to VCAM-1/NOX-1 signaling in cisplatin-induced cardiotoxicity.

Objectives: Cisplatin (CP) is frequently used in various types of cancers. The cardiotoxic effects of this agent limit its usage. Our study seeks to investigate the protective effects of Irbesartan (IRB) on CP-induced cardiotoxicity. Materials and Methods: The following four groups comprised thirty-two rats: control, CP, CP+IRB, and IRB. On the fourth day of the experiment, 5 mg/kg of CP was given to CP and CP+IRB groups intraperitoneally, and for seven days, water or IRB 50 mg/kg (orally) was administered. Vascular endothelial growth factor (VEGF), caspase-3 (Cas-3), vascular cell adhesion molecule-1 (VCAM-1), NADPH oxidase-1 (NOX-1), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) were measured. Results: The levels of VCAM-1, NOX-1, VEGF, Cas-3, and LDH were increased in the CP group. The treatment with IRB decreased VCAM-1, NOX-1, VEGF, Cas-3, and LDH levels significantly (P<0.05). Histopathological examination revealed normal heart architecture in Control and IRB groups. While marked hyperemia and myocardial cell degeneration were noticed in the CP group, significant amelioration was observed in the CP+IRB group. Aortas in the CP group showed endothelial damage and desquamation. IRB treatment markedly ameliorated histopathological findings in the CP+IRB group. Cardiac and aortic damage caused by CP was attenuated by IRB treatment owing to the anti-inflammatory and antiapoptotic effects of IRB. Conclusion: IRB may help reduce the severity of CP-induced cardiac injury by limiting leukocyte migration and reducing inflammation and apoptosis.

Investigation of cardioprotective effect of lercanidipine on doxorubicin-induced cardiotoxicity.

Although doxorubicin (DOX) is an effective anti-neoplastic drug for many types of cancer, particularly dose-related cardiotoxicity limits the use of the drug. In this study, it was aimed to investigate the protective effect of lercanidipine (LRD) against DOX-induced cardiotoxicity. In our study, 40 Wistar albino female rats were randomly divided into 5 groups as control, DOX, LRD 0.5 (DOX + 0.5 mg/kg LRD), LRD 1 (DOX + 1 mg/kg LRD), and LRD 2 (DOX + 2 mg/kg LRD). At the end of the experiment, the rats were sacrificed, and their blood, heart, and endothelial tissues were examined biochemically, histopathologically, immunohistochemically, and genetically. According to our findings, necrosis, tumor necrosis factor alpha activity, vascular endothelial growth factor activity, and oxidative stress were increased in the heart tissues of the DOX group. In addition, DOX treatment caused the deteriorations in biochemical parameters, and levels of autophagy-related proteins, Atg5, Beclin1, and LC3-I/II were detected. Significant dose-related improvements in these findings were observed with LRD treatment. Besides, Atg5, LC3-I/II, and Beclin1 levels evaluated by western blot revealed that LRD exerts a tissue protective effect by regulating autophagy in endothelial tissue. LRD treatment, which is a new-generation calcium channel blocker, showed antioxidant, anti-inflammatory, and anti-apoptotic properties in heart and endothelial tissue in a dose-dependent manner and also showed protective activity by regulating autophagy in endothelial tissue. With studies evaluating these mechanisms in more detail, the protective effects of LRD will be revealed more clearly.

Dexpanthenol protects against lipopolysaccharide-induced acute kidney injury by restoring aquaporin-2 levels via regulation of the silent information regulator 1 signaling pathway.

BACKGROUND: Acute kidney injury (AKI) is a serious pathology that causes dysfunction in concentrating urine due to kidney damage, resulting in blood pressure dysregulation and increased levels of toxic metabolites. Dexpanthenol (DEX), a pantothenic acid analog, exhibits anti-inflammatory and anti-apoptotic properties in various tissues. This study investigated the protective effects of DEX against systemic inflammation-induced AKI. METHODS: Thirty-two female rats were randomly assigned to the control, lipopolysaccharide (LPS), LPS+DEX, and DEX groups. LPS (5 mg/kg, single dose on the third day, 6 h before sacrifice) and DEX (500 mg/kg/d for 3 d) were administered intraperitoneally. After sacrifice, blood samples and kidney tissues were collected. Hematoxylin and eosin, caspase-3 (Cas-3), and tumor necrosis factor alpha (TNF-α) staining were performed on the kidney tissues. The total oxidant status (TOS) and total antioxidant status were measured using spectrophotometric methods. Aquaporin-2 (AQP-2), silent information regulator 1 (SIRT1), and interleukin-6 (IL-6) were detected using quantitative reverse transcription-polymerase chain reaction analysis. RESULTS: Histopathological analysis revealed that DEX treatment ameliorated histopathological changes. In the LPS group, an increase in the blood urea nitrogen, creatinine, urea, IL-6, Cas-3, TNF-α, and TOS levels and oxidative stress index was observed compared with the control group, whereas AQP-2 and SIRT1 levels decreased. DEX treatment reversed these effects. CONCLUSIONS: DEX was found to effectively prevent inflammation, oxidative stress, and apoptosis in the kidneys via the SIRT1 signaling pathway. These protective properties suggest DEX's potential as a therapeutic agent for the treatment of kidney pathologies.

Dexpanthenol ameliorates doxorubicin-induced lung injury by regulating endoplasmic reticulum stress and apoptosis.

Doxorubicin (DOX), which is used as a chemotherapeutic agent in the treatment of tumors, has limited use due to its toxicity in various organs and tissues. One of the organs where DOX has a toxic effect is the lung. DOX shows this effect by increasing oxidative stress, inflammation, and apoptosis. Dexpanthenol (DEX), a homologue of pantothenic acid, has anti-inflammatory, antioxidant, and anti-apoptotic properties. Therefore, the purpose of our investigation was to explore how DEX could counteract the harmful effects of DOX on the lungs. Thirty-two rats were used in the study, and 4 groups were formed (control, DOX, DOX + DEX, and DEX). In these groups, parameters of inflammation, ER stress, apoptosis, and oxidative stress were evaluated by immunohistochemistry, RT-qPCR, and spectrophotometric methods. In addition, lung tissue was evaluated histopathologically in the groups. While CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions increased in the DOX group, Bcl-2 gene expression levels significantly decreased. In addition, changes in Bax and Bcl-2 were supported immunohistochemically. There was a significant increase in oxidative stress parameters and a significant decrease in antioxidant levels. In addition, an increase in inflammatory marker (TNF-α and IL-10) levels was determined. There was a decrease in CHOP/GADD153, caspase-12, caspase-9, and Bax gene expressions and an increase in Bcl-2 gene expression in the DEX-treated group. In addition, it was determined that there was a decrease in oxidative stress levels and inflammatory findings. The curative effect of DEX was supported by histopathological findings. As a result, it was experimentally determined that DEX has a healing effect on oxidative stress, ER stress, inflammation, and apoptosis in lung damage caused by DOX toxicity.

The ß1 Adrenergic Blocker Nebivolol Ameliorates Development of Endotoxic Acute Lung Injury.

Acute lung injury (ALI) is a disease, with no effective treatment, which might result in death. Formations of excessive inflammation and oxidative stress are responsible for the pathophysiology of ALI. Nebivolol (NBL), a third-generation selective ß1 adrenoceptor antagonist, has protective pharmacological properties, such as anti-inflammatory, anti-apoptotic, and antioxidant functions. Consequently, we sought to assess the efficacy of NBL on a lipopolysaccharide (LPS)-induced ALI model via intercellular adhesion molecule-1 (ICAM-1) expression and the tissue inhibitor of metalloproteinases-1 (TIMP-1)/matrix metalloproteinases-2 (MMP-2) signaling. Thirty-two rats were split into four categories: control, LPS (5 mg/kg, intraperitoneally [IP], single dose), LPS (5 mg/kg, IP, one dosage 30 min after last NBL treatment), + NBL (10 mg/kg oral gavage for three days), and NBL (10 mg/kg oral gavage for three days). Six hours after the administration of LPS, the lung tissues of the rats were removed for histopathological, biochemical, gene expression, and immunohistochemical analyses. Oxidative stress markers such as total oxidant status and oxidative stress index levels, leukocyte transendothelial migration markers such as MMP-2, TIMP-1, and ICAM-1 expressions in the case of inflammation, and caspase-3 as an apoptotic marker, significantly increased in the LPS group. NBL therapy reversed all these changes. The results of this study suggest that NBL has utility as a potential therapeutic agent to dampen inflammation in other lung and tissue injury models.

Effect of methylenetetrahydrofolate reductase gene polymorphisms and oxidative stress in silent brain infarction.

Ischemic infarctions occur under the influence of genetic and environmental factors. In our study, the role of ischemia-modified albumin and thiol balance, which are new markers in determining oxidative damage together with MTHFR gene polymorphisms and homocysteine levels, in the development of SBI was investigated. White matter lesions in the magnetic resonance imaging (MRI) results of the patients were evaluated according to the Fazekas scale and divided into groups (Grade 0, 1, 2, and 3). Homocysteine, folate, B12, IMA, total thiol, and native thiol were measured by biochemical methods. The polymorphisms in MTHFR genes were investigated by the RT-PCR method. According to our results, a significant difference was found between the groups in age, homocysteine, folate, IMA, total thiol, and native thiol parameters (p < 0.05). When we compared the groups in terms of genotypes of the C677T gene, we found a significant difference in TT genotype between grades 0/3 and 1/3 (p < 0.05). We determined that homocysteine and IMA levels increased and folate levels decreased in CC/TT and CT/TT genotypes in the C677T gene (p < 0.05). Considering our results, the observation of homocysteine and IMA changes at the genotype level of the MTHFR C677T gene and between the groups, and the deterioration of thiol balance between the groups suggested that these markers can be used in the diagnosis of silent brain infarction.

Serum zonulin and claudin-5 levels in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study aimed to investigate serum zonulin and claudin-5 levels of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and healthy controls by controlling the parameters such as age, sex and body mass index (BMI) percentile which are known to affect these parameters. METHOD: A total of 80 treatment-naive children and adolescents with ADHD and 40 healthy volunteer controls aged 8-12 years were enrolled in this study. The severities of ADHD symptoms were assessed via parent- and teacher-rated questionnaires. The severity of anxiety and depression symptoms of the children were assessed by the self-report inventories. Serum levels of zonulin and claudin-5 were measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: The multivariate analysis of covariance (MANCOVA) revealed a significant main effect of groups in the serum zonulin and claudin-5 levels, an effect that was independent of age, sex and BMI percentile. Significant differences were found between the study groups in terms of serum log-claudin-5 levels. However, there was no significant difference between the study groups in terms of serum zonulin levels. CONCLUSION: These findings provide additional evidence for dysregulation of the blood-brain barrier, especially abnormalities in claudin-5 function, which may be involved in the aetiology of ADHD.Key pointsADHD is one of the most common neurodevelopmental disorders of childhood. Although ADHD is quite common, its aetiology has yet to be fully explained.In recent years, studies on the relationship between intestinal and blood-brain brain barrier permeability and psychiatric disorders have increased.In our study, serum claudin-5 levels were higher in the ADHD group compared to the control group, while serum zonulin levels did not differ between the groups.

Serum zonulin and claudin-5 levels in children with obsessive-compulsive disorder.

Background: Obsessive-compulsive disorder (OCD), a chronically debilitating neuropsychiatric disorder, is characterized by distinctive and recurrent obsessions and/or compulsions. An increasing number of evidence indicates that sophisticated interactions between different neurobiological factors play a part in OCD etiology, but the certain underlying mechanisms are still mainly unknown. The present research aimed to explore whether the concentrations of serum zonulin and claudin-5 vary between OCD patients and healthy controls. The present research also intended to explore whether there is an association between zonulin and claudin-5 concentrations and OCD severity.Methods: Twenty-four (13 boys and 11 girls) OCD patients and 24 (13 boys and 11 girls) healthy controls were included in this study. The clinical severity of the OCD symptoms was evaluated by the Children's Yale-Brown Obsessive-Compulsive Scale and the Maudsley Obsessive-Compulsive Inventory. Participants also filled out the Revised Child Anxiety and Depression Scales-Child Version to determine the anxiety and depression levels of the children. Venous blood samples were collected, and serum zonulin and claudin-5 levels were measured.Results: Serum claudin-5 levels were found to be significantly higher in OCD patient whereas serum zonulin levels were not significantly different between the groups.Conclusions: Taken together with our results, our study suggests that dysregulation of the blood-brain barrier, especially claudin-5, may be involved in the etiology of OCD.

Coenzyme Q10, Zinc and MDA levels in verruca vulgaris

Background/aim: Verruca vulgaris is a benign disease characterized with papillomas on the skin and mucosa. The aim of this study was to investigate the serum levels of coenzyme Q10, MDA, and zinc as well as the lipid profile of verruca vulgaris patients and examine the relationship between these parameters and clinical manifestations of the disease. Materials and methods: The study included 49 verruca vulgaris patients (mean age: 32.01 ± 14.20 years; 22 males, 27 females) and 40 healthy volunteers (mean age: 31.63 ± 8.98 years; 21 males and 19 females). Coenzyme Q10 levels were assessed by using an enzyme- linked immunosorbent assay. Serum MDA levels were measured spectrophotometrically. Zinc levels were measured using a Perkin Elmer AAnalyst 800 atomic absorption spectrometer with a deuterium background correction and additional standard techniques. Results: The coenzyme Q10 levels were found to be higher in the verruca vulgaris group compared to the healthy volunteers. However, this increase was not statistically significant (P = 0.195). Zinc levels were significantly lower in the verruca vulgaris group compared to the healthy volunteers (P = 0.002). In the patient group, MDA levels and HDL levels were significantly higher compared to the healthy volunteers (P = 0.023 and P = 0.004, respectively). Additionally, there was no statistically significant difference between the groups in the CoQ10/Total cholesterol ratio (P = 0.433). Conclusion: Reduced serum zinc levels and increase of oxidative stress in verruca vulgaris may be a factor responsible for development of verruca vulgaris.

Platelet indices (mean platelet volume and platelet distribution width) have correlations with periodontal inflamed surface area in coronary artery disease patients: A pilot study.

BACKGROUND: The plausible mechanisms regarding the relationship between periodontitis and coronary artery disease (CAD) has long been the focus of studies. This study aimed to test the hypothesis that higher periodontal inflamed surface area (PISA) values have positive correlations with increased complete blood parameters in patients with CAD. METHODS: Patients who underwent coronary angiography with a suspicion of CAD between the ages 30 to 75 years were included. Clinical periodontal parameters (probing depth [PD], clinical attachment loss, bleeding on probing) were recorded, and the participants were divided into four groups after the coronary angiography: group 1: CAD (+) with periodontitis (n = 20), group 2: CAD (+) without periodontitis (n = 20), group 3: CAD (-) with periodontitis (n = 21), group 4: CAD (-) without periodontitis (n = 16). Complete blood counts were analyzed regarding the differences and correlations between the investigated parameters. RESULTS: CAD (+) P (+) individuals had significantly higher platelet distribution width (PDW) values than the other groups (P < 0.0125). Positive lower correlations were found between PISA scores and mean platelet volume (MPV, P = 0.021, rho = 0.264), PISA and PDW (P = 0.240, rho = 0.036) in the whole study group; and moderate correlation between PD and red blood cell distribution width (RDW, P = 0.049, rho = 0.445) in CAD (-) groups with/without periodontitis were found. Age was found to predict CAD with o lower OR (1.17, P < 0.01). CONCLUSION: The results of the present study highlight some blood parameters (PDW, RDW, and MPV) in CAD patients with/without periodontitis in terms of the relationship between inflammatory diseases and their significant low and moderate correlations with PISA values.