The protective role of selenium against high-fructose corn syrup-induced kidney damage: a histopathological and molecular analysis.

With the growth of the food industry, fructose, the intake of which increases with food, causes obesity and metabolic syndrome. Kidney damage may develop from metabolic syndrome. Selenium (Se) participates in the structure of antioxidant enzymes and has a medicinal effect. In this work, the protective impact of Se on kidney damage produced by high-fructose corn syrup (HFCS) via endoplasmic reticulum (ER) stress was examined. The study comprised four groups, each consisting of ten experimental animals: control, HFCS (20%-HFCS), HFCS (20%-HFCS), + Se (0.3 mg/kg/day/po), and Se (0.3 mg/kg/day/po) alone. The duration of the experiment was 6 weeks. Kidney tissues were stained with hematoxylin and eosin for histological examination. Immunohistochemical analysis was conducted to assess TNF-α and caspase-3 levels. The spectrophotometric evaluation was performed to measure TOS (total oxidant status), TAS (total antioxidant status), and OSI (oxidative stress index) levels. The PERK, ATF4, CHOP, BCL-2, and caspase-9 gene expression levels were assessed by the RT-qPCR method. After Se treatment, histopathological abnormalities and TNF-α and caspase-3 levels in the HFCS+Se group decreased (p < 0.001). While TOS and OSI levels increased dramatically in the HFCS group, TAS values decreased significantly but improved after Se application (p < 0.001). The expression levels of the genes PERK, ATF4, CHOP, and caspase-9 were significantly lower in the HFCS group when compared to the HFCS+Se group (p < 0.05). Our findings suggest that Se may protect against ER stress, oxidative stress, apoptosis, and kidney damage caused by high-dose fructose consumption.

Effect of Laurus nobilis on bacteria and human transforming growth factor-ß1.

OBJECTIVE: In this study, we aimed to determine the phenolic compounds, the antibacterial activity of extract from Laurus nobilis leaves, and its possible effect on transforming growth factor-ß1 expression level in peripheral blood mononuclear cells. METHODS: The phenolic components of Laurus nobilis were identified by the high-performance liquid chromatography method. The antibacterial activity of this extract was determined by disk diffusion and broth microdilution methods. The transforming growth factor-ß1 expression was analyzed using the RT-qPCR method. RESULTS: Epicatechin was found in the highest amount and o-coumaric acid in the lowest amount. The half-maximal inhibitory concentration (IC50) was determined to be 55.17 µg/mL. The zones of inhibition and minimum inhibitory concentration for Staphylococcus aureus, Enterococcus faecalis, and Klebsiella pneumoniae were 15, 14, and 8 mm and 125, 250, and 1000 µg/mL, respectively. The change in transforming growth factor-ß1 expression levels was found to be statistically significant compared with the control groups (p<0.0001). CONCLUSION: Laurus nobilis extract was found to be effective against bacteria and altered the expression level of transforming growth factor-ß1 in peripheral blood mononuclear cells.

Standardizing urethral stricture models in rats: a comprehensive study on histomorphologic and molecular approach.

PURPOSE: To create a reproducible and standardized urethral stricture model in rats, evaluating both histomorphologic findings and gene expression data. In studies involving experimental animals, more standardization is needed for the creation of a urethral stricture model. METHODS: Sixteen male rats were randomized into two groups. The Sham group (n:8) underwent only a penoscrotal incision, while the stricture group (n:8) had their urethras exposed through a penoscrotal incision, followed by electrocauterization to the corpus spongiosum. On the 15th day, blood and urethral tissues were harvested for histologic and molecular analyses. Histomorphologic, immunohistochemical, and reverse transcription polymerase chain reaction analyses were performed. RESULTS: The stricture group exhibited more severe and intense spongiofibrosis, inflammation, epithelial desquamation, and congestion in vascular structures compared to the controls (p < 0.05). The urethral tissue in the stricture group showed an increased ratio of inflammation parameters, including Collagen 1A1, Collagen 3A1, elastin, Transforming growth factor ß1, α Smooth muscle actin, Platelet-derived growth factor α, and Platelet-derived growth factor ß. Transforming growth factor ß1, Platelet-derived growth factor α, and Platelet-derived growth factor ß each correlated highly with the other six parameters (r > 0.60, p < 0.05). CONCLUSION: Developing electrocoagulation-induced urethral stricture in rats is a simple, reliable, inexpensive, and reproducible. Reporting histologic data with qualitative and semi-quantitative scoring will enhance data standardization, aiding reader understanding and analysis. Transforming growth factor ß and Platelet-derived growth factor play key roles in fibrosis during stricture development. Incorporating these cytokines in urethral stricture animal model studies can demonstrate successful stenosis creation.

Lercanidipine alleviates doxorubicin-induced lung injury by regulating PERK/CHOP and Bax/Bcl 2/Cyt c pathways.

Doxorubicin (DOX), which is used to treat various cancers and hematological malignancies, has limited therapeutic application due to its toxicity in tissues and organs. These toxic effects occur through alterations in intracellular calcium regulation, elevated cell stress and oxidative damage, and increased apoptosis. Lercanidipine (LRD) is a long-acting antihypertensive calcium channel blocker with anti-inflammatory, anti-apoptotic, and antioxidant effects. The aim of this study was to investigate the effect of LRD on DOX-induced lung toxicity. Four groups (control, DOX, DOX + 0.5 LRD, and DOX + 2 LRD) totaling 32 rats were established. TNF-α levels in the lung tissues were detected by immunohistochemistry, and the tissues were subjected to histopathological examination. In determining oxidative stress, total antioxidant status (TAS) and total oxidative stress (TOS) were determined using spectrophotometry, and the oxidative stress index (OSI) value was calculated. The mRNA relative expression levels of the genes were evaluated by RT-qPCR. It was determined that inflammatory and oxidative stress markers and pro-apoptotic gene levels were increased and anti-apoptotic gene levels were decreased in the lung tissues of the DOX-administered group. In addition, histopathological changes were significantly increased. Although it was not statistically significant, inflammation, oxidative stress, and apoptosis were reduced, as were other histopathological indicators, in the group that received LRD (0.5 mg/kg). Inflammation, oxidative stress, and apoptosis were found to be statistically reduced and corroborated by histological findings in the group given LRD (2 mg/kg). In conclusion, it was determined that LRD had an ameliorative effect on DOX-induced lung toxicity in an experimental animal model.

Relationship between IL-17, TNF-α, IL-10, IFN-γ, and IL-18 polymorphisms with the outcome of hepatitis B virus infection in the Turkish population.

OBJECTIVE: Hepatitis B virus is a global threat that can lead to liver cirrhosis and hepatocellular carcinoma. For the treatment of chronic hepatitis B virus, polymorphisms might be an option for gene treatments. This study aimed to investigate the effects of IL-17, TNF-α, IL-10, IFN-γ, and IL-18 gene polymorphisms on hepatitis B virus infection in the Turkish population. METHODS: The genotypes and allele distribution of 75 patients exposed to hepatitis B virus and 50 healthy control individuals were analyzed. The real-time polymerase chain reaction method was used for identification. RESULTS: A correlation was observed between susceptibility to hepatitis B virus infection and IL-17 Exon 3/3'UTR (rs1974226) C, IL-17 Exon 3 (rs763780) A, IL-18 (-607) (rs1946518) A alleles, and IL-17 Exon 3 (rs763780) AA genotype (p=0.006, p=0.009, p=0.025, and p=0.008, respectively). Furthermore, IL-18 (-137) (rs187238) TT genotype and TNF-α-308 (rs1800629) G and A alleles, were associated with protection against hepatitis B virus infection (p=0.0351 and p=0.032, respectively). CONCLUSION: This study demonstrated that TNF-α (-308), IL-17 (Exon 3/3' UTR), IL-17 (Exon 3), and IL-18 (-607) polymorphisms are associated with hepatitis B virus infection. Therefore, these may serve as potential therapeutic targets for chronic viral hepatitis in the Turkish population.

miR-21, miR-221, and miR-222 upregulation in lung cancer promotes metastasis by reducing oxidative stress and apoptosis.

OBJECTIVE: The purpose of our research was to observe the effects of miR-21, miR-221, and miR-222, as well as their target genes on oxidative stress, lung cancer formation, and metastasis. METHODS: Positron emission tomography/computed tomography, fiberoptic bronchoscopy, and/or endobronchial ultrasonography were performed on a total of 69 lung cancer patients to detect the presence or absence of metastasis, and the patients were classified based on the types of cancer. Total RNA and miRNA were isolated from the obtained biopsy samples. The quantitative analysis of hsa-miR-21-5p, hsa-miR-222-3p, and hsa-miR-221-3p and their target genes was performed by the RT-qPCR method. In determining oxidative stress, total antioxidant status and total oxidant status in tissue and total thiol and native thiol in blood were determined spectrophotometrically. OSI and disulfide were calculated. RESULTS: We discovered that the metastasis group had higher levels of hsa-miR-21-5p, hsa-miR-221-3p, and hsa-miR-222-3p (p<0.05). While TIMP3, PTEN, and apoptotic genes decreased in metastasis, anti-apoptotic genes increased (p<0.05). In addition, while oxidative stress decreased in the metastasis group, no change was found in the serum (p>0.05). CONCLUSION: Our findings show that upregulation of hsa-miR-21-5p, hsa-miR-221-3p, and hsa-miR-222-3p effectively contributes to both proliferation and invasion by influencing oxidative stress and mitochondrial apoptosis.

Irbesartan has a curative effect on lipopolysaccharide-induced cardiotoxicity by antioxidant and antiapoptotic pathways.

INTRODUCTION AND OBJECTIVE: Lipopolysaccharide (LPS) has been associated with myocardial inflammation, oxidative stress, apoptosis, and cardiac dysfunction, as well as death by causing sepsis. In this study, we investigated the effect of irbesartan (IRB), an angiotensin receptor antagonist, on cardiotoxicity caused by LPS. METHODS: The experiment involved 24 Wistar albino rats divided into three groups of eight: control, LPS (5 mg/kg), and LPS (5 mg/kg)+IRB (3 mg/kg). Parameters including total oxidative status, total antioxidant status, oxidative stress index, and ischemia-modified albumin were measured to assess oxidative stress in heart tissues and serum. Serum CK, CK-MB, and LDH levels were measured spectrophotometrically. RT-qPCR was used to detect the mRNA expression levels of Bcl-2, BAX, p53, caspase-3, and sirtuin 1. Tissues taken from the heart and aorta were examined by immunohistochemistry and histopathology. RESULTS: While there was an increase in the parameters indicating heart damage, oxidative stress, and apoptosis in the group given LPS, there was an improvement in all parameters and heart damage in the group treated with IRB. CONCLUSION: As a result of our study, we determined that IRB has an ameliorating effect on myocardial damage caused by oxidative stress and apoptosis developed by the LPS-induced sepsis model.

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.

Investigation of inflammation, oxidative stress, and DNA damage in COVID-19 patients.

COVID-19 disease, which spreads worldwide, is a disease characterized by widespread inflammation and affects many organs, especially the lungs. The resulting inflammation can lead to reactive oxygen radicals, leading to oxidative DNA damage. The pneumonia severity of 95 hospitalized patients with positive RT-PCR test was determined and divided into three groups: mild, moderate, and severe/critical. Inflammation markers (neutrophil-lymphocyte ratio, serum reactive protein, procalcitonin, etc.) were determined, and IL-10 and IFN-γ measurements were analyzed using the enzyme-linked immunosorbent assay method. In evaluating oxidative damage, total thiol, native thiol, disulfide, and ischemia-modified albumin (IMA) levels were determined by measuring spectrophotometrically. The comet assay method's percentage of tail DNA obtained was used to determine oxidative DNA damage. As a result, when the mild and severe/critical groups were compared, we found that total thiol, native thiol, and disulfide levels decreased significantly in the severe/critical group due to the increase in inflammation markers and cytokine levels (p < 0.05). We could not detect any significance in IMA levels between the groups (p > 0.05). At the same time, we determined an increase in the tail DNA percent level, that is, DNA damage, due to the increased oxidative effect. As a result, we determined that inflammation and oxidative stress increased in patients with severe pneumonia, and there was DNA damage in these patients.

Selenium exerts protective effects on inflammatory cardiovascular damage: molecular aspects via SIRT1/p53 and Cyt-c/Cas-3 pathways.

BACKGROUND: Systemic inflammatory response could affect many systems. Cardiac dysfunction develops due to cardiovascular system damage and could be mortal. Selenium is a trace element that can be used as a dietary supplement and has antioxidant, anti-inflammatory, and anti-apoptotic properties. This study aims to evaluate the protective effects of selenium on cardiovascular damage via silenced information regulator 1 (SIRT1)/p53 and cytochrome C (Cyt-c)/ caspase-3 (Cas-3) pathways. METHODS AND RESULTS: Thirty-two rats were randomly divided into 4 groups as control, LPS (0.1 mg/kg, intraperitoneally(i.p.), 2-7 days) and LPS + Selenium (LPS-0.1 mg/kg, i.p., 2-7 days, selenium - 100 µg/kg, i.p., 1-7 days) and selenium (100 µg/kg, i.p., 1-7 days) group. On the 8th day of the experiment, rats were sacrificed. Blood samples and half of the left ventricles were collected for biochemical and genetic analysis. The remaining left ventricles and aorta were taken for histological and immunohistochemical analysis. In the LPS group myocardial hemorrhages, hyperemia, and endothelial cell loss were observed. Also, Cas-3 and vascular endothelial growth factor (VEGF) expressions; creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), ischemia modified albumin (IMA), total oxidant status (TOS), oxidative stress index (OSI) levels; p53, Cyt-c, Cas-3 mRNA expressions increased while total antioxidant status (TAS) levels, glutathione peroxidase (GPx) activity, SIRT1 mRNA expression decreased. Selenium treatment reversed all these changes. CONCLUSION: Selenium showed protective effects on cardiovascular injury via regulating SIRT1/p53 and Cyt-c/Cas-3 pathways. This study enlightened the possible usage of selenium on cardiotoxicity.

Irbesartan decreased mitochondrial stress related apoptosis in cisplatin induced acute kidney injury via regulating BCL-2/BAX signaling.

BACKGROUND: Cisplatin (CPN) is used in the treatment of various cancers. However, the especially nephrotoxic effect is limiting its use. We aimed to evaluate the renoprotective effects of Irbesartan (IBN) on CPN-induced acute kidney injury via mitochondrial stress related apoptosis. METHODS AND RESULTS: 32 rats were divided into 4 groups as control, CPN, CPN + IBN and IBN. Water or IBN 50 mg/kg (orally) was administered for 7 days and a single dose of CPN (5 mg/kg) intraperitoneally was given CPN and CPN + IBN groups on fourth day of experiment. At the end of the experiment, serum BUN and creatinine (Cre) levels, which are the indicators of kidney function are measured. Bcl-2-associated X protein (Bax) and B-cell-lymphoma-2 (Bcl-2) mRNA levels were analyzed by using qRT-PCR from kidneys as a mitochondrial stress indicator. Also, active caspase-3(cas-3) protein and tumor necrosis factor alpha (TNF-α) expressions were examined by immunostaining of the kidney tissues. For evaluation of oxidative stress, malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels of renal tissues were measured and oxidative stress index (OSI) were calculated. CPN increased serum BUN and creatinine levels. Also, MDA, TOS and OSI levels were significantly elevated and TAS levels decreased in the CPN group. Moreover, CPN elevated the levels of Bax, active cas-3 protein and TNF-α expressions and suppressed Bcl-2 levels. IBN treatment reversed all these changes. CONCLUSIONS: IBN significantly regressed kidney damage by its anti-inflammatory and antioxidant activity via inhibiting mitochondrial stress. IBN could be used as a renoprotective agent in CPN-induced kidney injury.

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.

Comparison of DNA damage and proliferative capacities in smear samples of HPV positive and negative patients by micronucleus counting and AgNOR staining.

Human papillomavirus (HPV) is believed to cause cervical cancer. Thousands of women develop cancer and other diseases caused by HPV each year. HPV 16 and 18 types are found in approximately 70% of cervical cancers. Micronuclei are small chromosomal fragments that are considered indicators of DNA damage. AgNOR positive dots are useful for assessing proliferation. We investigated the relation between HPV-DNA, micronuclei and AgNOR in smear samples. Three groups were defined: HPV negative, 16/18 positive and other high-risk groups (31, 33, 35, 39, 45, 51, 52, 56, 58, 66 and 68) (HR). After typing, micronuclei were identified by Papanicolaou staining and AgNOR regions were detected by silver staining. Serum reactive protein (CRP) also was measured. We found that the average age of HPV negative patients was significantly greater than for the HPV positive groups. We also found that CRP levels were significantly higher in the HPV 16/18 positive group than HPV negative and other HPV group. We found that the number of micronuclei in the HPV 16/18 group was significantly greater than for the HPV negative group. Also, we found that AgNOR staining for the HPV 16/18 group was significantly greater than for the HPV negative group. We found that CRP level, cell proliferation and genome instability were increased in HPV positive patients. The AgNOR and micronucleus tests were useful for evaluating cell proliferation and DNA damage.

HLA-DRB1 allele frequency and immunological response in obstructive sleep apnea syndrome in Turkish population.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is a complex, polygenic and multifactorial disease. The relationship between Human Leukocyte Antigen (HLA) polymorphisms and sleep disturbances has been established, but the relationship with HLA alleles has not been fully clarified. In addition, sleep deprivation in OSAS patients can cause changes that affect the components and responses of the immune system. OBJECTIVE: The aim of this study has assessed the effect of HLA-DRB1 alleles on OSAS disease and the changes occurring in immune response cells in Turkish population. METHOD: OSAS was diagnosed by polysomnography and severity was determined. PCR SSP and flow cytometry methods were used. RESULTS: We found that DRB1*07 and DRB1*11 were significantly increased in the control group and DRB1*03 and DRB1*08 alleles in the patient group in our study (P = 0.048, P = 0.005, P = 0.012 and P = 0.030, respectively). DRB1*08 was significantly increased in patients with severe OSAS (P = 0.002). When the immunological response was examined in OSAS patients, there was a decrease in CD4, an increase in HLA DR, CD8 and NK cells (P = 0.002, P = 0.00, P = 0.020, P = 0.040, respectively). We also found that CD19 was reduced in severe OSAS (P = 0.048). CONCLUSION: These results suggest that the DRB1*03 allele may play a predisposing role in OSAS disease and that the DRB1*08 allele may be related to the severity of the disease. In addition, the decrease in CD4, CD8, NK and HLA DR increase in this disease suggests that the disease causes impairment of the immunological system and may be associated with autoimmunity.