Restorative effects of Chrysin pretreatment on oxidant–antioxidant status,inflammatory cytokine production,and apoptotic and autophagic markers in acute paracetamol‐induced hepatotoxicity in rats: An experimental and biochemical study

Paracetamol (PC) is a widely used analgesic and antipyretic drug, but it leads to acute hepatotoxicity at high doses intakes. This study was aimed to investigate the effects of Chrysin (CR) on hepatotoxicity constituted at high doses of PC in rats. Rats were subjected to oral pretreatment of CR (25 and 50 mg/kg b.w.) via feeding needle for 6 days against hepatotoxicity induced by a single dose of PC (500 mg/kg b.w.) administered orally via feeding needles. Although PC increases lipid peroxidation and liver enzyme activities, it has led to reduction of antioxidant enzyme activities. PC induced inflammatory responses by increasing the levels of TNF‐α and IL‐1β. Furthermore, PC caused apoptosis and autophagy by increasing activity of Caspase‐3 and LC3B level. On the other hand, CR therapy significantly regulated these values in rats. This study demonstrated that CR possesses restorative effect against PC‐induced hepatotoxicity by suppressing oxidative stress, inflammation, and apoptotic and autophagic tissue damage.     

Effect of weight loss on P wave dispersion in obese subjects

Objective: The aim of this study was to investigate effect of loss weight on P wave dispersion in obese subjects. Research Methods and Procedures: After a 12‐week weight loss program (diet and medical therapy), a total of 30 (24 women and six men) obese subjects who had lost at least 10% of their original weight were included in the present study. All subjects underwent a routine standard 12‐lead surface electrocardiogram. Electrocardiograms were transferred to a personal computer by a scanner and then magnified 400 times by Adobe Photoshop software (Adobe Systems, Mountain View, CA). P wave dispersion, which is also defined as the difference between the maximum P wave duration and the minimum P wave duration, was also calculated. Results: After a 12‐week weight loss program, BMI (p < 0.001), maximum P wave duration (p < 0.001), and P wave dispersion (p < 0.001) significantly decreased. The mean percentage of weight loss was 13% (10% to 20.3%). The decrease in the level of P wave dispersion (21 ± 10 and 7 ± 12 ms, p < 0.002) was more prominent in Group II (≥12% loss of their original weight) than Group I (<12% loss of their original weight) after the weight loss program. A statistically significant correlation between decrease in the level of P wave dispersion and percentage of weight loss was found (r = 0.624, p < 0.001). Discussion: Substantial weight loss in obese subjects is associated with a decrease of P wave duration and dispersion. Therefore, these observations suggest that substantial weight loss is associated with improvement in atrial repolarization abnormalities in obese subjects.     

Disruption of PTPRO causes childhood-onset nephrotic syndrome

Idiopathic nephrotic syndrome (INS) is a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema. Because it typically results in end-stage kidney disease, the steroid-resistant subtype (SRNS) of INS is especially important when it occurs in children. The present study included 29 affected and 22 normal individuals from 17 SRNS families; genome-wide analysis was performed with Affymetrix 250K SNP arrays followed by homozygosity mapping. A large homozygous stretch on chromosomal region 12p12 was identified in one consanguineous family with two affected siblings. Direct sequencing of protein tyrosine phosphatase receptor type O (PTPRO; also known as glomerular epithelial protein-1 [GLEPP1]) showed homozygous c.2627+1G>T donor splice-site mutation. This mutation causes skipping of the evolutionarily conserved exon 16 (p.Glu854_Trp876del) at the RNA level. Immunohistochemistry with GLEPP1 antibody showed a similar staining pattern in the podocytes of the diseased and control kidney tissues. We used a highly polymorphic intragenic DNA marker-D12S1303-to search for homozygosity in 120 Turkish and 13 non-Turkish individuals in the PodoNet registry. This analysis yielded 17 candidate families, and a distinct homozygous c.2745+1G>A donor splice-site mutation in PTPRO was further identified via DNA sequencing in a second Turkish family. This mutation causes skipping of exon 19, and this introduces a premature stop codon at the very beginning of exon 20 (p.Asn888Lysfs*3) and causes degradation of mRNA via nonsense-mediated decay. Immunohistochemical analysis showed complete absence of immunoreactive PTPRO. Ultrastructural alterations, such as diffuse foot process fusion and extensive microvillus transformation of podocytes, were observed via electron microscopy in both families. The present study introduces mutations in PTPRO as another cause of autosomal-recessive nephrotic syndrome.     

Formation of Umbilicaria decussata (Antarctic and Turkey) Extracts Based Nanoflowers with Their Peroxidase Mimic,Dye Degradation and Antimicrobial Properties

This work describes a unique and environmentally friendly approach for creating three-dimensional (3D) organic-inorganic flower shaped hybrid nanostructures called “nanoflower (NF)” by using Umbilicaria decussate (U. decussate) extract and copper ions (Cu²⁺). U. decussate species were collected from certain place in Antarctic and Turkey and extraction of each species were completed in methanol and water. The U. decussate extracts were used as organic components and Cu²⁺ acted as inorganic components for formation of U. decussate extracts based hybrid NFs. We rationally used these NFs as novel nanobiocatalyst and antimicrobial agents. These NFs exhibited peroxidase mimic, dye degradation and antimicrobial properties. The NFs were characterized with various techniques. For instance, the morphologies of the NFs were monitored by scanning electron microscope (SEM), presence of elements in the NFs were presented using Energy Dispersive X-Ray Analysis (EDX). Fourier-transform infrared spectroscopy (FT-IR) was used to elucidate corresponding bending and stretching of bonds in the NFs. The NFs acted as effective Fenton agents in the presence of hydrogen peroxide, and we demonstrated their peroxidase-like activity against guaiacol, dye degradation property towards malachite green and antimicrobial activity for Aeromonas hydrophila, Aeromonas sobria, Escherichia coli, Salmonella enterica and Staphylococcus aureus.     

Evaluation of cytotoxic,antifungal, and larvicidal activities of different bis-sulfonamide Schiff base compounds

Schiff bases (imines or azomethines) are versatile ligands synthesized from the condensation of amino compounds with active carbonyl groups and used for many pharmaceutical and medicinal applications. In our study, we aimed to determine the cytotoxic, antifungal and larvicidal activities of biologically potent bis-sulfonamide Schiff base derivatives that were re-synthesized by us. For this aim, 16 compounds were re-synthesized and tested for their cytotoxic, antifungal and larvicidal properties. Among this series, compounds A1B2 , A1B4 , A4B2 , A4B3 , and A4B4 were shown to have cytotoxic activity against tested cancer lung cell line (A549). The most potent antifungal activity was observed in compounds A2B1 and A2B2 against all fungi. A1B1 showed the strongest larvicidal effect at all concentrations at the 72nd h (100% mortality). These obtained results demonstrate that these type of bis-substituted compounds might be used as biologically potent pharmacophores against different types of diseases.     

Antimicrobial activity of some Satureja essential oils

The genus Satureja is represented by fifteen species of which five are endemic and Satureja pilosa and S. icarica have recently been found as new records for Turkey. Aerial parts of the Satureja pilosa, S. icarica, S. boissieri and S. coerulea collected from different localities in Turkey were subjected to hydrodistillation to yield essential oils which were subsequently analysed by GC and GC/MS. The main constituents of the oils were identified, and both antibacterial and antifungal bioassays were applied. Carvacrol (59.2%, 44.8%, 42.1%) was the main component in the oils of S. icarica, S. boissieri and S. pilosa, respectively. The oil of S. coerulea contained beta-caryophyllene (10.6%) and caryophyllene oxide (8.0%) as main constituents.     

Protective effects of taxifolin on pazopanib-induced liver toxicity: an experimental rat model

Pazopanib is a tyrosine kinase inhibitor that is generally used for the treatment of metastatic renal cell cancer and advanced soft tissue sarcoma. It can cause various degrees of hepatotoxicity. Our study aimed to investigate the effect of taxifolin on pazopanib-induced liver toxicity. A total of 18 rats were divided into three groups: the pazopanib (PP), pazopanib plus taxifolin (TPP), and control (C) group. Taxifolin was administered to the TPP (n=6) group with a dose of 50 mg/kg. Distilled water was orally admnistered to the C (n=6) and PP (n=6) groups as a solvent. Subsequently, pazopanib 200 mg/kg was administered to the TPP and PP groups via the stomach. This procedure was repeated once a day for four weeks. Then, all rats were sacrificed, and their livers were removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), and total antioxidant status (TAS) levels were evaluated. MDA and TOS levels were higher in the PP group compared with the levels of the other parameters (P<0.001). tGSH and TAS levels were lower in the PP group than in the TPP and C groups (P<0.001), and the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were higher. Furthermore, liver tissue damage, including hemorrhage, hydropic degeneration, and necrosis was observed in the PP group. Administration of taxifolin before pazopanib significantly improved degenerative changes. Our study demonstrated that the administration of taxifolin is significantly effective in preventing pazopanib-induced hepatotoxicity in rats.     

Effects of<Emphasis Type="Italic">Nigella sativa</Emphasis> and human parathyroid hormone on bone mass and strength in diabetic rats

Osteoporosis is a major complication in patients with diabetes mellitus (DM), particularly in those with insulin dependency. Recently, many therapeutic effects ofNigella sativa L. (NS) extracts have been exhibited such as anti-inflammatory, antitumor, and antidiabetic with clinical and experimental studies. Mechanical strength in the femur and vertebrae increases with human parathyroid hormone (hPTH) treatment. The aim of the present study was to test the hypothesis that combined treatment with NS and hPTH is more effective than treatment with NS or hPTH alone in improving bone mass, connectivity, and biomechanical behavior using the finite element method (FEM) in insulin-dependent diabetic rats. In the mechanical analysis, five rat bones (control, diabetic diabetic NS treated, diabetic hPTH treated, and diabetic NS + hPTH treated) have been studied for bending analysis using the finite element analysis program ANSYS. Combined treatment of NS and hPTH was more effective on bone histomorphometry and mechanical strength than treatment with NS or hPTH alone for streptozotocin-induced diabetic osteopenia, which notably decreased bone volume.