Hepatoprotective potentials of Usnea longissima Ach. and Xanthoparmelia somloensis (Gyelnik) Hale extracts in ethanol-induced liver injury.

In our study, the antioxidant and anti-inflammatory effects of different lichen applications were investigated in rats using an experimental ethanol toxicity model. 48 rats were used in the study and they were divided into 6 groups with 8 rats in each group. These groups were: control, ethanol (2 g/kg), ethanol + Usnea longissima Ach. (200 mg/kg), ethanol + Usnea longissima Ach. (400 mg/kg), ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (100 mg/kg) and ethanol + Xanthoparmelia somloensis (Gyelnik) Hale (200 mg/kg). The experimental work continued for 21 days. Lichen extracts and ethanol were administered by gavage to rats divided into groups. According to the experimental protocol, the experimental animals were sacrificed and their liver tissues were isolated. Biochemical parameters in serum, histological examinations, oxidative stress and inflammation parameters both at biochemical and molecular level in liver tissues were performed. Oxidative stress and inflammatory response were increased in the liver tissue of rats treated with ethanol for 21 days, and liver functions were impaired. It was found that U. longissima and X. somloensis extracts showed good antioxidant activity and conferred protective effects against ethanol-induced oxidative stress and inflammation. This could be attributed to the presence of secondary metabolites in the extract, which act as natural antioxidants and could be responsible for increasing the defence mechanisms against free radical production induced by ethanol administration.

Determination of the effects of fusaric acid, a mycotoxin, on cytotoxicity, gamma-H2AX, 8-hydroxy-2 deoxyguanosine and DNA repair gene expressions in pancreatic cancer cells.

Pancreatic cancer has a poor prognosis and is an important public health problem for developing countries. Oxidative stress plays an important role in cancer initiation, progression, proliferation, invasion, angiogenesis and metastasis. For this reason, one of the important strategic targets of new cancer therapeutics is to drive cancer cells into apoptosis through oxidative stress. In nuclear and mitochondrial DNA, 8-hydroxy-2'-deoxyguanosine and gamma-H2AX (γ-H2AX) are used as important oxidative stress biomarkers. Fusaric acid (FA) is a mycotoxin that mediates toxicity produced by Fusarium species and exhibits anticancer effects in various cancers via inducing apoptosis, cell cycle arrest, or other cellular mechanisms. The aim of this study was to determine the effects of fusaric acid on cytotoxic and oxidative damage in MIA PaCa-2 and PANC-1 cell lines. In this context, dose and time dependent cytotoxic effect of fusaric acid was determined by XTT method, mRNA expression levels of genes related to DNA repair were determined by RT-PCR, and its effect on 8-hydroxy-2'-deoxyguanosine and γ-H2AX levels was revealed by ELISA assay. According to XTT results, fusaric acid inhibits cell proliferation in MIA PaCa-2 and Panc-1 cells in a dose- and time-dependent manner. IC50 doses were determined as 187.74 µM at 48 h in MIA PaCa-2 cells and 134.83 µM at 48 h in PANC-1 cells, respectively. γ-H2AX and 8-OHdG changes were not found significant in pancreatic cancer cells. The mRNA expression levels of DNA repair-related genes NEIL1, OGG1, XRCC and Apex-1 change with exposure to fusaric acid. This study contributes to the therapeutic approaches to be developed for pancreatic cancer and demonstrates the potential of fusaric acid as an anticancer agent.

Exploring of the ameliorative effects of Nerium (Nerium oleander L.) ethanolic flower extract in streptozotocin induced diabetic rats via biochemical, histological and molecular aspects.

BACKGROUND: Nerium oleander L. is ethnopharmacologically used for diabetes. Our aim was to investigate the ameliorative effects of ethanolic Nerium flower extract (NFE) in STZ-induced diabetic rats. METHODS: Seven random groups including control group, NFE group (50 mg/kg), diabetic group, glibenclamide group and NFE treated groups (25 mg/kg, 75 mg/kg, and 225 mg/kg) were composed of forty-nine rats. Blood glucose level, glycated hemoglobin (HbA1c), insulin level, liver damage parameters and lipid profile parameters were investigated. Antioxidant defense system enzyme activities and reduced glutathione (GSH) and malondialdehyde (MDA) contents and immunotoxic and neurotoxic parameters were determined in liver tissue. Additionally, the ameliorative effects of NFE were histopathologically examined in liver. mRNA levels of SLC2A2 gene encoding glucose transporter 2 protein were measured by quantitative real time PCR. RESULTS: NFE caused decrease in glucose level and HbA1c and increase in insulin and C-peptide levels. Additionally, NFE improved liver damage biomarkers and lipid profile parameters in serum. Moreover, lipid peroxidation was prevented and antioxidant enzyme activities in liver were regulated by NFE treatment. Furthermore, anti-immunotoxic and anti-neurotoxic effects of NFE were determined in liver tissue of diabetic rats. Histopathogically, significant liver damages were observed in the diabetic rats. Histopathological changes were decreased partially in the 225 mg/kg NFE treated group. SLC2A2 gene expression in liver of diabetic rats significantly reduced compared to healthy rats and NFE treatment (25 mg/kg) caused increase in gene expression. CONCLUSION: Flower extract of Nerium plant may have an antidiabetic potential due to its high phytochemical content.

Potential human health risks of toxic/harmful elements by consumption of Pseudevernia furfuracea.

The potential human health risks of some toxic/harmful elements related to the consumption of Pseudevernia furfuracea (L.) Zopf. were investigated. The toxic/harmful elements (cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), nickel (Ni), and zinc (Zn)) were determined in P. furfuracea. According to the analysis result, the maximum (max.) toxic/harmful element value was 62 ± 3.1 mg/kg for Mn and minimum (min.) value was 0.19 ± 0.01 mg/kg for Cd. The estimated daily exposure doses (EDEXDs) for men, women and children were dietary (bread) > dietary (tea) > dermal. For dietary (bread) and dietary (tea) non-carcinogenic (HQ) risk was children > women > men. For dermal, HQ risk was women > children > men. Hazard index (HI) value for men was >1 for Cr. HI value for men was 1.36 for Cr. HI value for women was >1 for Cr and Mn. HI values for women were 1.54 for Cr and 1.01 for Mn. Also, the HI value for children was >1 for Cr, Mn, and Pb. HI values for children were 3.44 for Cr, 2.24 for Mn, and 1.66 for Pb. This situation showed that there was a non-carcinogenic risk. Carcinogenic risk values were dietary (bread) > dietary (tea) > dermal. The total max. carcinogenic value was 1.97E-03 for Cr while the total min. carcinogenic value was 1.31E-05 for Pb. As a result, it has been determined that there may be a risk of cancer due to the consumption of lichen as bread and this situation may adversely affect human health.

Prophylactic effect of myricetin and apigenin against lipopolysaccharide-induced acute liver injury.

BACKGROUND: Liver has an important role in the initiation and progression of multiple organ failure that occurs in sepsis. Many natural active substances can be used to reduce the liver injury caused by sepsis. For this aim, the effects of myricetin and apigenin on mice model of acute liver injury was evaluated in this study. METHODS AND RESULTS: Thirty-six mice were randomly divided into six groups as; control, lipopolysaccharide (LPS) (5 mg/kg), LPS + myricetin (100 mg/kg), LPS + myricetin (200 mg/kg), LPS + apigenin (100 mg/kg), and LPS + apigenin (200 mg/kg) groups. Myricetin and apigenin were administered orally for 7 days, and LPS was administered intraperitoneally only on the 7th day of the study. 24 h after LPS application, all animals were sacrificed and serum biochemical parameters, histopathology and oxidative stress and inflammation markers of liver tissue were examined. Myricetin and apigenin pre-treatments increased serum albumin and total protein levels, liver GSH level and catalase and SOD activities and decreased serum ALT, AST, ALP, γ-GT, CRP, total and direct bilirubin levels, liver MPO activity, MDA, NOx, PGE2, TNF-α, IL-1ß, and IL-6 levels, iNOS and COX-2 mRNA levels, phosphorylation of NF-κB p65, IκB, and IKK proteins but not p38, ERK, and JNK proteins in LPS-treated mice. Myricetin and apigenin administration also regained the hepatic architecture disrupted during LPS application. CONCLUSION: Myricetin and apigenin pre-treatments led to reduction of liver injury indices and oxidative stress and inflammatory events and these flavonoids has probably hepatoprotective effects in acute liver injury.

Cytogenetic and Oxidative Status of Cultured Lymphocytes after Exposure to Extracts from Rhizopogon Mushrooms (Agaricomycetes) In Vitro.

In this study, acetone and water extracts obtained from edible mushrooms, Rhizopogon luteolus Fr. and Rh. roseolus (Corda) Th. Fr., containing important bioactive components were used. Total antioxidant capacity (TAC) and total oxidative stress (TOS) levels were examined on human peripheral lymphocyte culture treated with the respective extracts. Levels of genetic damage and cytotoxic effects of the respective extracts on lymphocytes were also tested. In general, when TAC levels of the extracts on cells were examined, a concentration-dependent increase was observed; a negative correlation was found between TOS data and concentration. Genotoxicity tests (chromosome aberration and micronucleus analysis) revealed that the concentrations of the extract applications did not significantly (P > 0.05) change genotoxicity on human peripheral lymphocyte culture compared to the negative control. Considering all of the results obtained, it was determined that applications of Rh. luteolus and Rh. roseolus extracts, especially at concentrations of 50 and 100 mg/L, increased the TAC value of lymphocytes, which play an important role in the human immune system, without causing genetic or oxidative stress.

Role of Adenosine Deaminase in Patients with Erythematotelangiectatic Rosacea and Demodex folliculorum Positivity.

BACKGROUND: Adenosine deaminase (ADA) is an aminohydrolase involved in the catabolism of purine nucleotides and irreversibly deaminizes adenosine and deoxyadenosine to inosine and deoxyinosine. ADA enzyme deficiency results in the loss of functional properties of B and T lymphocytes. Demodex species have been reported to be transmitted between humans through close contact and to play a role in the pathogenesis of rosacea, acne vulgaris, perioral dermatitis, seborrhoeic dermatitis, micropapillary-pruritic dermatitis and blepharitis. The present study aimed to compare serum ADA levels in D. folliculorum positive patients with the healthy control individuals. METHODS: Serum ADA levels were examined for 30 patients diagnosed with erythematotelangiectatic rosacea and 40 healthy individuals in Malatya Inonu University in 2017. Standardized skin surface biopsy (SSSB) method was used to diagnose D. folliculorum. A significant decrease was found in the ADA levels of Demodex-positive rosacea patients when compared to the control group. RESULTS: ADA levels were decreased in the Demodex-positive group. The mean ADA level in patient group was significantly lower than the mean in the control group (P<0.001). There was no significant difference between the patient and control groups in terms of age and gender. CONCLUSION: During and after treatment of Demodex-positive rosacea patients, determination of ADA levels may give more detailed information on the immune mechanisms.

The Efficacy of Posterior Subtenon Triamcinolone Acetonide Injection in Treatment of Irvine-Gass Syndrome.

Purpose: To evaluate the efficacy and safety of posterior 40 mg subtenon triamcinolone acetonide (PST) injection in treating Irvine-Gass syndrome.Methods: The retrospective study included 21 patients (mean age: 76 ± 8.2) with a treatment-naïve eye subjected to topical anesthesia and injection of 40 mg/ml triamcinolone via a blunt tip SubTenon cannula through a single inferonasal peritomy. Best corrected visual acuity (BCVA; logMAR), intraocular pressure (IOP), biomicroscopic and funduscopic findings, and optical coherence tomography (OCT) measurements were recorded.Results: Baseline central macular thickness decreased from 431 ± 136 µm to 300 ± 67 µm (1st month; p = .002), to 292 ± 56 µm (3rd month; p = .002), and to 299 ± 66 µm (6th month; p = .005). Mean BCVA increased from 0.71 ± 0.23 to 0.27 ± 0.11, 0.19 ± 0.06, and 0.24 ± 0.17, respectively (all visits; p < 0.001). Mean IOP values did not change significantly (p = .12).Conclusion: PST injection is an effective and safe treatment for Irvine-Gass syndrome.

Investigation of Insulin-Like Growth Factor-1 (IGF-1), P53, and Wilms' Tumor 1 (WT1) Expression Levels in the Colon Polyp Subtypes in Colon Cancer.

BACKGROUND There is no study in the literature investigating the expression levels of WT1, p53, and IGF-1 in colon polyp subtypes. In this study, we aimed to investigate the expression levels of IGF-1, p53, and WT1 in colon polyp subtypes and to determine whether expression levels are correlated with each other. MATERIAL AND METHODS Tissue specimens were obtained from 105 patients (80 men, 25 women; age range, 30-91 years) who underwent surgical resection for colorectal cancer (CRC) at Ordu University School of Medicine, Department of Pathology between January 2015 and 2017. Parameters such as age, sex, region of origin, and pathological diagnosis type were determined. The preparations were immunohistochemically stained with corresponding markers. RESULTS The results of the study showed that there was a statistically significant relationship between WT1 expression (negative - positive) in polyps and the place where the sample was taken (P=0.011). There is a positive relationship between P53 staining score (0-3) and positive frequency of IGF-1 (60.9-85.7%). There was a statistically significant change in P53 scores and location (P=0.006, p=0.015, respectively). As the P53 score of the polyps increased (0 to 3), the rate of adenomatous (34.8-78.4%) increased, so a positive relationship was found. WT1 and IGF-1 gene expression was associated with tumor location, p53 staining score, and sex. CONCLUSIONS WT1 and IGF-1 are appropriate markers for CRC, and WT1 expression in CRC primary tumors especially could be a novel independent marker for prognosis and tumor progression.

The effect of acute organophosphate intoxication on female rat hippocampus cornu ammonis region pyramidal neuron numbers, biochemistry and morphology.

BACKGROUND: The most commonly used insecticides and pesticides worldwide are organophosphate compounds, chemicals that irreversibly inhibit the cholinesterase enzyme. Acute intoxication with cholinesterase inhibitors is known to cause permanent effects on both the human and rat brains. AIM: To investigate the effect of acute organophosphate intoxication on hippocampus morphology, biochemistry, and pyramidal neuron numbers in female rats. METHODS: Twenty-one rats were randomly divided into three groups. The control group received normal nutrition and underwent no procedures. The sham group received intraperitoneal physiological serum, while the experimental group received intraperitoneal 0.8 g/kg fenthion. Rats were sacrificed 24 h after these procedures. The brains were removed and divided in two halves medially, with one side being kept in 10% neutral formalin. After fixation procedures, tissues were embedded in blocks, sliced, and stained. A neuron count was then performed for the hippocampus. The other hippocampus was homogenized and used for biochemical procedures. RESULTS: Hippocampus sections from rats in the experimental group exhibited swelling and loss of shape in pyramidal cells, while no changes were observed in the control or sham groups. The number of neurons in the experimental group was lower than in the control and sham groups. Biochemical analysis revealed higher MDA and GSH values in the experimental group compared to the control and sham groups. CONCLUSION: Our results show increased apoptotic neurodegeneration of cells in the cornu ammonis region of the hippocampus and changes in biochemical values in rats with acute organophosphate exposure.