Effects of fisetin on ethanol-induced rewarding properties in mice.

Background: Alcohol use disorder (AUD) is a chronic relapsing disorder associated with compulsive drinking of alcohol. Natural flavonoid fisetin affects a variety of transmitter systems relevant to AUD, such as aminobutyric acid, N-methyl-D-aspartate, and dopamine, as well as peroxisome proliferator-activated receptors.Objectives: This study investigated fisetin's impact on the motivational properties of ethanol using conditioned place preference (CPP) in mice (n = 50).Methods: Mice were conditioned with ethanol (2 g/kg, i.p.) or saline on alternating days for 8 consecutive days and were given intragastric (i.g.) fisetin (10, 20, or 30 mg/kg, i.g.), 45 min before ethanol conditioning. During extinction, physiological saline was injected to the control and ethanol groups, and fisetin was administered to the fisetin groups. To evaluate the effect of fisetin on the reinstatement of ethanol-induced CPP, fisetin was given 45 min before a priming dose of ethanol (0.4 g/kg, i.p.; reinstatement test day).Results: Fisetin decreased the acquisition of ethanol-induced CPP (30 mg/kg, p < .05) and accelerated extinction (20 and 30 mg/kg, p < .05). Furthermore, fisetin attenuated reinstatement of ethanol-induced CPP (30 mg/kg, p < .05).Conclusions: Fisetin appears to diminish the rewarding properties of ethanol, as indicated by its inhibitory effect and facilitation of extinction in ethanol-induced CPP. These findings imply a potential therapeutic application of fisetin in preventing ethanol-seeking behavior, promoting extinction, and reducing the risk of relapse.

Protective roles of some natural and synthetic aromatase inhibitors in testicular insufficiency caused by Bisphenol A exposure.

In our study, the protective role of synthetic aromatase inhibitors anastrozole (ANS), letrozole (LTZ) and exemestane (EXM) and natural aromatase inhibitors resveratrol (RSV) and apigenin (APG) against testicular failure caused by exposure to Bisphenol A (BPA) was investigated. The epididymal sperm concentration, sperm motility and sperm morphology were determined. Oxidative stress and inflammatory response parameters were examined and histological examinations were performed in testicular tissues. Our results revealed that BPA exposure decreased serum testosterone and estrogen levels, increased FSH and LH levels (p < 0.05). BPA has been found to increase oxidative stress and inflammatory response and disrupt the histological structure. Also, BPA exposure decreased testicular weight, epididymal sperm concentration and motility, and increased abnormal sperm rate (p < 0.05). These results show that ANS, LTZ and RSV treatments reduce the BPA-induced testicular damage.

Boswellic Acid and Betulinic Acid Pre-treatments Can Prevent the Nephrotoxicity Caused by Cyclophosphamide Induction.

Cyclophosphamide (CYP) is a chemotherapeutic drug used to treat various cancers. However, its clinical use is limited due to severe organ damage, particularly to the kidneys. While several phytochemicals have been identified as potential therapeutic targets for CYP nephrotoxicity, the nephroprotective effects of boswellic acid (BOSW) and betulinic acid (BET) have not yet been investigated. Our study used 42 rats divided into six equal groups. The study included six groups: control, CYP (200 mg/kg), CYP+BOSW20 (20 mg/kg), CYP+BOSW40 (40 mg/kg), CYP+BET20 (20 mg/kg), and CYP+BET40 (40 mg/kg). The pre-treatments with BOSW and BET lasted for 14 days, while the application of cyclophosphamide was performed intraperitoneally only on the 4th day of the study. After the experimental protocol, the animals were sacrificed, and their kidney tissues were isolated. Renal function parameters, histological examination, oxidative stress, and inflammation parameters were assessed both biochemically and at the molecular level in kidney tissue. The results showed that oxidative stress and inflammatory response were increased in the kidney tissue of rats treated with CYP, leading to impaired renal histology and function parameters (p < 0.05). Oral administration of both doses of BET and especially high doses of BOSW improved biochemical, oxidative, and inflammatory parameters significantly (p < 0.05). Histological studies also showed the restoration of normal kidney tissue architecture. BOSW and BET have promising biological activity against CYP-induced nephrotoxicity by attenuating inflammation and oxidative stress and enhancing antioxidant status.

Protective role of resveratrol and apigenin against toxic effects of bisphenol a in rat salivary gland.

OBJECTIVES: The aim of this study was to investigate the cellular changes caused by Bisphenol A (BPA) exposure in salivary gland cells and to examine the protective role of resveratrol (RSV) and apigenin (APG) molecules against the negative effects of BPA. MATERIALS AND METHODS: Forty-two rats were randomly divided into 6 groups as; (i) control, (ii) BPA (130 mg/kg), (iii) BPA + RSV100 (100 mg/kg), (iv) BPA + RSV200 (200 mg/kg), (v) BPA + APG100 (100 mg/kg), and (vi) BPA + APG200 (200 mg/kg). In all experimental groups, the chemicals were given by gavage every day for a total of 28 days. RESULTS: The BPA administration caused a significant increase in tissue oxidative stress parameters as opposed to a significant decrease in tissue antioxidant levels (p < 0.05). On the other hand, it was observed that RSV and APG treatment reversed this situation (p < 0.05). The BPA administration did not cause a significant change in tissue prostaglandin E2 (PGE2) and nitric oxide levels, whereas low-dose RSV significantly reduced the tissue PGE2 levels compared to BPA (p < 0.05). BPA caused cytopathological changes and apoptosis in salivary gland cells. In the BPA group, edema, nuclear pleomorphism, and pyknotic nuclei were observed. Moreover, both RSV and APG were found to provide protection against BPA-induced cellular damage, while RSV provided better cellular protection than APG. The control group had a normal histological structure. CONCLUSION: BPA caused cytopathological changes and apoptosis in salivary gland cells. As a result, it was observed that these phytochemicals probably have cytoprotective effects in BPA intoxication.

Investigation of the impact of antiparasitic drug moxidectin on the rewarding effects of alcohol.

Alcohol addiction or alcoholism constitutes a significant risk factor worldwide for morbidity and mortality. Moxidectin is a recently approved anthelmintic drug, which also activates the gamma-aminobutyric acid receptors. The objective of the present study was to examine the impact of moxidectin on rewarding effects of ethanol in the conditioned place preference (CPP) model in mice. In separate experiments, mice were administered intraperitoneal (i.p.) injections of moxidectin (5 or 10 mg/kg, i.p.) before a) acquisition of alcohol-induced CPP, b) each extinction session, and c) alcohol-induced reinstatement of CPP. The present experiments provide consistent data about ethanol place preference in mice (2 g/kg, i.p.), with mice in all tests spending significantly more time on the ethanol-paired side. The acquisition of the CPP response to ethanol was prevented by the administration of moxidectin at a dose of 10 mg/kg. Additionally, moxidectin treatment accelerated the extinction of ethanol CPP when given repeatedly during the extinction phase. Ethanol-induced reinstatement of CPP following an extinction phase was inhibited by moxidectin. Ethanol alone and co-administration with moxidectin did not change locomotor activity and motor coordination. In conclusion, we suggest that moxidectin may be a promising therapeutic candidate for prevention of ethanol-induced addiction and relapse as well as detoxification.

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.

Ni and Cr impurities profile in Valeriana officinalis L., radix-based herbal medicinal product available in polish pharmacies due to ICH Q3D guideline.

Elemental impurities (EIs) profiling in final pharmaceutical products is often not adequately treated, however it is crucial problem in pharmaceutical analysis by reason of the various regulatory authorities (like ICH Q3D guideline). EIs in pharmaceuticals may arise from numerous sources of which the herbal ingredients are not a frequent subject of pharmaceutical analyses. However, based on number of traditional use registrations per year for herbal medicinal products (HMPs) in the EU, it can be stated that monocomponent HMPs are still very popular for use. Due to the high frequency of use, exposure to EIs from HMPs may be high during long-term use. The aim of our article was Ni and Cr impurities profiling of Valeriana officinalis L., radix (Valerian root) as an example of the HMP available in Polish pharmacies for the relief of mild nervous tension and sleep disorders. The choice of metals was justified by: (1) a single dose of Ni administered via oral route can induce dermatitis in nickel-sensitised individuals; (2) Cr is a very problematic element from toxicological point of view. Our results indicate that the standards of the ICH Q3D guideline are met for all EIs.

Protective effect of myricetin, apigenin, and hesperidin pretreatments on cyclophosphamide-induced immunosuppression.

Aim: Major side effects of cyclophosphamide administration are immunosuppression and myelosuppression. The immunomodulatory effects of plant bioactive compounds on chemotherapy drug-induced immunosuppression may have significant effects in cancer treatment. For this reason, we investigated the immunomodulatory effect of myricetin, apigenin, and hesperidin in cyclophosphamide-induced immunosuppression in rats.Methods: In our study, a total of 64 rats were used, and divided into eight equal groups. These groups were: control, cyclophosphamide, cyclophosphamide + myricetin (100 mg/kg), cyclophosphamide + myricetin (200 mg/kg), cyclophosphamide + apigenin (100 mg/kg), cyclophosphamide + apigenin (200 mg/kg), cyclophosphamide + hesperidin (100 mg/kg), and cyclophosphamide + hesperidin (200 mg/kg). Myricetin, apigenin, and hesperidin pretreatments were performed for 14 d, while cyclophosphamide application (200 mg/kg) was performed only on the 4th day of the study. Levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, and natural killer cell cytotoxicity were determined. In addition, we measured pro-inflammatory cytokines, and followed lipid peroxidation and antioxidant markers and examined the histology of bone marrow, liver and spleen in all groups.Results: During cyclophosphamide treatment, all three phytochemicals increased the levels of humoral antibody production, quantitative hemolysis, macrophage phagocytosis, splenic lymphocyte proliferation, antioxidant markers, and natural killer cell cytotoxicity. Moreover, the agents decreased the levels of pro-inflammatory cytokines and mediators, reduced lipid peroxidation markers, and reduced tissue damage in liver, spleen, and bone marrow.Conclusion: Our study demonstrated that myricetin, apigenin, and hesperidin can reduce the immunosuppressive effect of cyclophosphamide by enhancing both innate and adaptive immune responses, and these compounds may be useful immunomodulatory agents during cancer chemotherapy.

Punicalagin induces apoptosis in A549 cell line through mitochondria-mediated pathway.

Lung cancer is the most common cause of cancer-related deaths worldwide. Punicalagin is an ellagitannin mostly found in pomegranate husk and shows very strong antitumoral activity. The purpose of this study was to investigate the mechanism in which punicalagin acts as an antiproliferative agent on A549 cell line (adenocarcinomic human alveolar basal epithelial cells) and MRC-5 cell line (normal lung fibroblast cells). The cultured cells were treated with punicalagin at concentrations of 1-100 µM for 24 h. For this aim, cell growth inhibition, percentage of apoptotic cells, cell cycle distribution, morphological changes, cellular and mitochondrial reactive oxygen species (ROS) production, and expression of apoptotic proteins were evaluated. Cell viability test and morphological examinations showed that punicalagin at 50 and 75 µM concentrations exhibited toxic effect against lung cancer cells but not toxic against normal lung cells. Cytoplasmic ROS production decreased with the application of punicalagin, while the level of ROS released from mitochondria increased due to mitochondrial dysfunction. Studies of apoptosis indicated that both punicalagin concentrations induced apoptotic process in A549 cells. However, cell cycle was arrested in the G1/S phase after punicalagin treatment. These findings suggest that punicalagin has antiproliferative and apoptotic properties in these concentrations.

Myricetin inhibits angiotensin converting enzyme and induces nitric oxide production in HUVEC cell line.

Nitric oxide is known as relaxing factor because it acts as a vasodilator, increases blood flow, and inhibits platelet aggregation and adhesion, on the other hand nitric oxide can modulate cellular and physiological processes to limit oxidative injury, limiting processes such as leukocyte adhesion. As the complete mechanism of myricetin and its cardiovascular benefits is not completely understood, the aim of this study was to investigate the antihypertensive activity of myricetin in human umbilical vein endothelial cell (HUVEC). Angiotensin converting enzyme (ACE) activity, nitric oxide production, reactive oxygen species (ROS) scavenger activity, cellular calcium concentration, and endothelial nitric oxide synthase (eNOS) activity and protein expression was investigated in HUVEC treated with different concentration of myricetin (1-60 µM). Myricetin increased nitric oxide production in HUVEC through decreased ROS levels and increased nitric oxide production and eNOS activation. Activation of eNOS enzyme was achieved by an increase of cellular calcium concentration. At the same examined concentration of myricetin, the activity of ACE was significantly inhibited. These findings indicate that myricetin may be helpful for lowering blood pressure; this could be achieved through dietary intervention or by the production of new antihypertensive treatments from a natural product.

Roe protein hydrolysate of Alburnus tarichi induces apoptosis in breast cancer MCF-7 and MDA-MB-231 cells through a caspase-dependent pathway.

The protein hydrolysates of fishes have been reported to be a potential source of many health benefits components for pharmaceutical or nutritional applications. The aim of this study is to examine the possible antiproliferative function of roe protein hydrolysates of Alburnus tarichi using enzymatic hydrolysis against breast cancer cells and explore its detailed mechanisms. In addition, we evaluated the effects of protein hydrolysate on the proliferation and apoptosis of two human breast cancer cell lines (MCF-7 and MDA-MB-231). The cultured cells were treated with protein hydrolysate at concentrations of 0-5 µg/ml for 24 h and 48 h. Inhibition of cell proliferation, percentage of apoptotic cells, cell cycle distribution, morphological changes, DNA fragmentation, intracellular reactive oxygen species (ROS) production, and apoptotic protein levels were also examined. Decreases in proliferation of MCF-7 and MDA-MB-231 cells were observed after treatment with the protein hydrolysate in a dose-dependent manner. Distinct morphological changes, a typical pattern of fragmented DNA, and increased intracellular ROS production and apoptotic protein levels were observed in both cell lines after hydrolysate treatment (p < 0.05). The results suggested that the protein hydrolysate inhibits the proliferation of human breast cancer cell lines by introducing apoptosis through a caspase-dependent pathway in a dose-dependent manner.

Prophylactic effect of Biochanin A in lipopolysaccharide-stimulated BV2 microglial cells.

Aim/Purpose of the study:Inhibition of microglial activation using phytochemicals may be a potential candidate for the prevention of neurodegenerative diseases caused by neuroinflammation and oxidative stress. The goal of this study was to investigate the protective role of Biochanin A on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. BV2 microglial cells were treated with LPS in the presence and absence of Biochanin A. Materials and methods: For this aim, nitric oxide production, nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), IL-6, Prostaglandin E2 (PGE2), and reactive oxygen species (ROS) levels, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), myeloid differentiation factor-88 (MyD88), and toll like receptor-4 (TLR-4) protein expressions, Akt and ERK1/2 phosphorylation levels were measured. Results:Biochanin A pretreatment resulted in significant and concentration-dependently reduced the LPS-induced production of nitric oxide, NF-κB p65, TNF-α, IL-1ß, IL-6, PGE2, and ROS compared to the untreated group. Biochanin A prophylaxis exerted an anti-inflammatory effect by suppressing iNOS, COX-2, MyD88, and TLR-4 protein expressions and Akt and ERK1/2 pathway activation. Conclusion:Taken together, these results show that Biochanin A exerts antioxidant and anti-inflammatory activities, thus may be beneficial for preventing neurodegenerative diseases mediated by microglial cells.

PAI-1 and tPA gene polymorphisms and susceptibility to chronic obstructive pulmonary disease in a sample of Turkish population.

OBJECTIVES: The aim of this study was to assess the influence of plasminogen activator inhibitor-1 (PAI-1) 4G/5G or tissue plasminogen activator (tPA) I/D polymorphisms in chronic obstructive pulmonary disease (COPD) cases in a sample of Turkish population. METHODS: PAI-1 4G/5G and tPA Alu-repeat I/D genetic polymorphisms in 153 COPD subjects and 160 controls were investigated using PCR-RFLP and PCR methods, respectively. RESULTS: 4G allele frequency was 0.62 and 0.39 for COPD and control groups, respectively. 4G allele had an estimated 2.56- fold [95% CI = 1.85-3.53] increased risk of COPD. tPA I allele frequency was 0.55 and 0.50, for COPD and control groups, respectively. I allele had an estimated 1.19-fold [95% CI = 0.87-1.62] increased risk of COPD. CONCLUSIONS: PAI-1 4G/4G and 4G/5G genotypes seemed to play a key role in the pathophysiology of COPD in Turkish individuals.

Diosmin suppresses the proinflammatory mediators in lipopolysaccharide-induced RAW264.7 macrophages via NF-κB and MAPKs signal pathways.

Diosmin is an unsaturated flavonoid glycoside, presents in citrus fruits. The aim of this study is to investigate the molecular mechanism of diosmin with respect to the NF-κB and MAPKs signaling pathways. Firstly, 10, 20, 30, 40 and 50 µM diosmin were treated to lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The anti-inflammatory effects of diosmin was displayed via measuring prostaglandin E2 (PGE2), nitric oxide (NO), interleukines (IL-6, IL-12), tumor necrosis factor α (TNF-α) production, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), IL-6, IL-12, TNF-α mRNA levels, and phosphorylation levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκB-α) and mitogen-activated protein kinases (MAPKs); JNK, ERK, and p38 in LPS induced RAW264.7 macrophages. Our study showed that especially high concentrations of diosmin decreased NO, PGE2, IL-6, IL-12, TNF-α production and mRNA levels of these mediators (p < 0.05). The expression of phosphorylated-JNK was significantly suppressed by diosmin at 40 and 50 µM concentrations. Furthermore, diosmin significantly inhibited the expression of phosphorylated-ERK, p38, and p-IκB-α in a dose-dependent manner. Our results suggest that diosmin is a potent anti-inflammatory agent and has potential for development into a therapeutic agent for inflammation-associated disorders.

Is Nasal Polyposis Related to Levels of Serum Vitamin D and Vitamin D Receptor Gene Expression?

BACKGROUND Nasal polyposis (NP) is the most frequent cause of nasal masses. Despite considerable research on the subject, its etiology has not been fully elucidated, and effective treatment methods have not been developed. Some etiological factors causing low or high expression of genes in genetically predisposed individuals may play a role in the pathogenesis of the disease. The purpose of this study was to assess the relation between levels of vitamin D receptor (VDR) gene expression and serum vitamin D with NP. MATERIAL AND METHODS The study included 46 subjects with NP (NP group) and 40 volunteers (control group). Nasal polyp tissue samples were taken from the NP group and nasal mucosa samples were taken from the control group. Levels of VDR gene expression in the tissue samples were assessed using the real-time polymerase chain reaction (RT-PCR) method. RESULTS Mean serum 25(OH)D levels were 13.38±14.08 ng/ml in the NP group and 10.57±6.44 ng/ml in the control group (p=0.249). VDR gene expression was present in 17.5% of the NP group and 3.3% of the control group, and the difference between the 2 groups was statistically significant (likelihood ratio χ²=3.887; p=0.049). CONCLUSIONS This is the first study to assess levels of VDR gene expression in subjects with NP. Our results suggest that VDR gene expression may be associated with the pathogenesis or progression of NP.

Determination of Genotoxic Effects of Hookah Smoking by Micronucleus and Chromosome Aberration Methods.

BACKGROUND Use of a hookah (a type of water pipe) is a traditional way of smoking tobacco, particularly in the Middle East. In Turkey, its popularity has been growing in recent years, especially among young people. It is known that cigarette smoking has genotoxic effects and causes mutations, but no comprehensive study has been done on the genotoxic effects of hookah usage, particularly in Turkey. MATERIAL AND METHODS We collected peripheral blood/buccal smear samples from 30 subjects who did not smoke cigarettes but who regularly smoke a hookah an average of 2 times per week, and from 30 control subjects who had never smoked cigarettes or a hookah. Chromosome analyses were performed on the samples obtained from peripheral blood of each individual, 25 metaphase plaques were counted for each, and chromosome/chromatid breakage/gap parameters were evaluated. Micronucleus analysis was done on buccal smear samples and micronucleus/binucleus parameters were investigated by counting 2000 cells of each individual. RESULTS Chromosome breakage ratios were found to be 0.64±0.86 and 0.46±0.71 in the study and control groups, respectively, while chromatid breakage ratios were 0.53±0.83 and 0.53±0.71; fragment ratios were 0.82±1.24 and 0.21±0.49 (p<0.05); and gap ratios were 0.57±0.83 and 0.18±0.53 (p<0.05), respectively. Micronucleus ratio was 6.03±2.06 and 4.43±2.27 (p<0.05) in the study and control groups, respectively, and binucleus ratios were 8.53±3.23 and 12.15±5.18, respectively (p<0.05). CONCLUSIONS Results of our study reveal significant statistical differences between the individuals who smoked hookah and those who did not in terms of fragment, gap, micronucleus, and binucleus parameters, suggesting that smoking a hookah may cause genotoxic effects.

Antioxidant activities of curcumin in allergic rhinitis.

We investigated the antioxidant effects of curcumin in an experimental rat model of allergic rhinitis (AR). Female Wistar albino rats (n = 34) were divided randomly into four groups: healthy rats (control group, n = 8), AR with no treatment (AR + NoTr group, n = 10), AR with azelastine HCl treatment (AR + Aze group, n = 8), and AR with curcumin treatment (AR + Curc group, n = 8). On day 28, total blood IgE levels were measured. For measurement of antioxidant activity, the glutathione (GSH) level and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities were measured in both inferior turbinate tissue and serum. Malondialdehyde (MDA) levels were measured only in inferior turbinate tissue, and paraoxonase (PON) and arylesterase (ARE) activities were measured only in serum. Statistically significant differences were found for all antioxidant measurements (GSH levels and CAT, SOD, GSH-Px activities in the serum and tissue, MDA levels in the tissue, and PON and ARE activities in the serum) between the four groups. In the curcumin group, serum SOD, ARE, and PON and tissue GSH values were higher than the control group. Moreover, tissue GSH levels and serum GSH-Px activities in the curcumin group were higher than in the AR + NoTr group. In the azelastine group, except MDA, antioxidant measurement values were lower than in the other groups. Curcumin may help to increase antioxidant enzymes and decrease oxidative stress in allergic rhinitis. We recommend curcumin to decrease oxidative stress in allergic rhinitis.

[Investigation of the association between chronic hepatitis B and C infections and TNF-α (-308) gene polymorphism]. / Kronik hepatit B ve C enfeksiyonlari ile TNF-α (-308) gen polimorfi zmi arasindaki iliskinin arastirilmasi.

Cytokines and genetic factors play important roles in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC) infections. Variations in cytokine genes may effect the gene expression and may lead to changes in the clinical manifestations of diseases. One of the single nucleotide polymorphisms in the promoter region of tumor necrosis factor-alpha (TNF-α) gene is the polymorphism at -308. position which was investigated in many studies by means of its relationship between CHB and CHC infections, however their results are incompatible. Furthermore, there is no sufficient data on this subject in our country. This study was aimed to determine the relationship between TNF-α(-308) gene polymorphism with CHB and CHC infections. A total of 271 patients with chronic hepatitis and 181 healthy subjects were included in the study. Of them 167 were CHB cases (67 female, 100 male; age range 18-74 years, mean age: 40.23 ± 13.09) and 95 controls for CHB group (46 female, 49 male; mean age: 36.41 ± 15.0 years), while 104 were CHC cases (63 female, 41 male; age range: 25-79 years, mean age: 52.8 ± 12.6) and 86 controls for CHC group (41 female, 45 male; mean age: 36.4 ± 14.9 years). After the isolation of genomic DNA from blood samples of the patient and control groups, TNF-α(-308)G/A (rs 1800629) polymorphism was investigated by using the real-time polymerase chain reaction from the obtained DNAs. Among CHB group, TNF-α(-308) GG, GA, AA genotypes were detected in 126 (75.4%), 38 (22.8%) and 3 (1.8%) of the patients, respectively, while these numbers were 84 (88.4%), 11 (11.6%) and 0 (0%) in control group, respectively. Among CHC group, TNF-α(-308) GG, GA, AA genotypes were detected in 37 (35.6%), 28 (26.9%) and 39 (37.5%) of the patients, respectively, while these numbers were 38 (44.2%), 8 (9.3%) and 40 (46.5%) in control group, respectively. The frequency of GA genotype was significantly higher in both patient groups compared to the control groups (p=0.024 for CHB and p= 0.006 for CHC). When the distribution of allele frequencies of TNF-α(-308)G/A polymorphism was evaluated in the patients and control groups, it was noted that G allele was found to be high in CHB patients comparing with controls (94.2% vs 86.8%), however A allele was identified to be lower than controls (5.8% vs 13.2%) (p= 0.008). In contrast, there was no significant difference in terms of allele frequency compared with CHC patients and the control group (p= 0.969). In conclusion, our data in accordance with the results of many studies in literature, determined that TNF-α(-308) polymorphisms can influence the chronicity of hepatitis B and C infections. Further studies on this subject would contribute to the elucidation of the molecular mechanisms of chronic hepatitis B and C diseases.

Assessment of liver volume with computed tomography and comparison of findings with ultrasonography.

BACKGROUND AND PURPOSE: In this study, we aimed to investigate the impact of non-alcoholic hepatic steatosis on the liver volume. As investigating hepatic steatosis, we utilized computed tomography (CT) to determine the degree of steatosis and we utilized hepatobiliary ultrasonography (USG) for densitometry and correlation. MATERIALS AND METHODS: As hepatosteatosis group, 35 patients over 18 years of age and whose abdominal CT scans were requested by several clinics and performed routinely were included in this study, and as control group, 40 healthy subjects without hepatosteatosis (clinically and radiologically) and correlated with hepatosteatosis group in terms of age and gender were included in this study. CT densitometry and liver attenuation index (LAI) of all individuals who participated in our study were calculated, and contrast images of patients were transferred to CT-Volume Software (Siemens Syngo Multimodality Workplace; Version VE52A). In this study, interactive and automated volume measurement techniques were used together. The volumes were measured separately in patient and control group. RESULTS: In this study for each stage in USG, there was found a direct correlation in terms of LAI and volume, and this correlation was statistically significant (p < 0.01). Furthermore, statistical significance between size and USG stage draws attention (p < 0.05). A significance relationship between USG stage and age could not be determined. CONCLUSION: As a result, we have reached the conclusion that CT densitometry can be used as an assistive technique along with USG to determine the degree of steatosis in the non-alcoholic fatty liver disease, and there is a positive linear correlation between the liver size and volume, and liver volume increases in the non-alcoholic fatty liver disease.

The neuroprotective effect of cornus MAS on brain tissue of Wistar rats.

Cornelian cherry (Cornus mas) is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer's disease) or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet). This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma.