Mistletoe (Viscum album L.) extract attenuates itraconazole-induced acute oxidative stress and hepatocellular injury in rats.

In the current study, the protective effect of a mistletoe extract (Helixor®, HLX) on Itraconazole (ITZ)-induced hepatocellular injury and acute oxidative stress in rats was aimed to be investigated by histological, biochemical and comet assay methods. Four groups a control group, an HLX group (5mg/kg/14days/intraperitoneally (ip)), an ITZ group (100mg/kg/14days/oral) and an HLX plus ITZ group (5mg/kg/14days/ip+100mg/kg/14days/oral) were all created from 32 female Wistar albino rats. At the end of the experiment, AST and ALT liver enzymes, total oxidant status (TOS) levels and total antioxidant status (TAS) levels, histopathological analysis and comet assay were carried out. Highest genotoxicity, higher levels of plasma AST and ALT, higher TOS, more degeneration of liver histopathology including hepatocyte degeneration, hepatocyte apoptosis and necrosis, portal/periportal inflammation, bile ductus hyperplasia and multinuclear giant cell formation were observed in ITZ group (p<0.05). As opposed to that, administration of HLX plus ITZ improved histopathological changes and DNA damage and showed a dramatic decrease in AST, ALT and TOS levels (p<0.05) and an increase in TAS level (p<0.001) when compared to ITZ group. This study showed that the antioxidant properties of HLX administration significantly decreased acute oxidative stress and hepatocellular damage in rats given ITZ.

Evaluation of the protective effect of silibinin against diazinon induced hepatotoxicity and free-radical damage in rat liver.

BACKGROUND: Diazinon (0,0-Diethyl 0-(1-6-methyl-2-isoprophyl 4 pyrimidinyl) phosphorothioate) (DI) is a very effective organophosphate pesticide, used widely in agriculture. Consequently, data on poisoning cases secondary to DI exposure are important. The DI may affect a variety of tissues, including liver. Silibinin is a pharmacologically active constitute of Silybum marianum, with documented antioxidant activity. OBJECTIVES: The aim of our study was to evaluate both histopathologically and biochemically whether silibinin is protective in DI induced liver damage. MATERIALS AND METHODS: Thirty two Wistar albino rats were divided into four groups, as follows: 1) control group - oral corn oil was given; 2) DI group - rats were administered orally 335 mg/kg in the corn oil solution; 3) Silibinin group - 100 mg/kg/day silibinin was given alone orally, every 24 hours for 7 days; 4) Silibinin + DI group - DI plus silibinin was given. All rats were sacrificed at the end of experiment. Superoxide dismutases (SOD), glutathione peroxidase (GPX), nitric oxide (NO) and myeloperoxidase (MPO) were investigated in serum and liver tissue. In addition, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzyme activities were evaluated. The liver tissue was evaluated histopathologically with Hematoxilin & Eosin dye. RESULTS: Biochemically, ALT, AST, NO, MPO in serum and NO, MPO in liver tissue were found to be significantly higher in DI group, compared to control group (P < 0.001). In Group Silibinin + DI, serum AST, ALT, NO, MPO levels were significantly lower (P < 0.01), and both serum and tissue SOD activities were significantly higher, compared to DI group (P < 0.001). Diazinon induced histopathological changes in liver tissue were: severe sinusoidal dilatation, moderate disruption of the radial alignment of hepatocytes around the central vein, severe vacuolization in the hepatocyte cytoplasm, inflammation around central vein and portal region. In rats receiving both DI and silibinin, the DI induced changes accounted for less sinusoidal dilatation, vacuolization in the hepatocyte cytoplasm and the inflammation around central vein and portal region (P < 0.05). CONCLUSIONS: The DI was found to induce liver damage by oxidative stress mechanisms. Silibinin reduced the oxidative stress by inducing antioxidant mechanisms, thereby showing protective effect against DI induced liver damage. Further studies with silibinin should be performed regarding DI toxicity.

Evaluation of the protective effect of silibinin in rats with liver damage caused by itraconazole.

Itraconazole (ITZ) belongs to the triazole group of antifungals with potent keratinophilic and lipophilic features. Hepatotoxicity is one of its most remarkable features. Silibinin (SIL) is a plant used worldwide which is used in the treatment of many liver diseases and it is especially very well known for its hepatoprotective-cytoprotective effect. The aim of our study was to research the protective effect of SIL in ITZ-induced hepatotoxicity using biochemical and pathological tests. Liver enzymes and antioxidant enzyme activities were measured spectrophotometrically by using commercial kits. ALT and AST levels in ITZ group were significantly increased compared to the group, while the activities of GSH-Px and SOD had decreased (p < 0.05). When ITZ group was compared to ITZ + SIL group, AST, ALT, and levels of NO and MPO were significantly decreased, while the activities of GSH-Px and SOD were increased (p < 0.05). Histopathological evaluation showed that SIL significantly decreased periportal inflammation and parenchymal hepatocyte apoptosis in ITZ and ITZ + SIL groups (p < 0.05). Eventhough not statistically significant, partial improvement with the use of SIL has been detected (p > 0.05) in hepatocyte degeneration and multinuclear giant cell formation. According to the evaluation performed with comet assay method, ITZ leads to DNA damage, and the use of SIL significantly decreases DNA damage (p < 0.05). We have detected that the use of ITZ increases oxidative stress (MPO, NO), decreases antioxidant activity (SOD and GSH-Px), and leads to DNA damage and histopathological liver damage, whereas the use of SIL has a cytoprotective effect on the liver by increasing the antioxidant effect (SOD, GSH-Px) and by decreasing the oxidative stress (NO, MPO). ITZ causes the generation of ROS and leads to DNA damage and liver damage. SIL has a cytoprotective effect on the liver by increasing antioxidant enzyme activities, preventing the formation of ROS.

Genetic variants of estrogen beta and leptin receptors may cause gynecomastia in adolescent.

OBJECTIVE: Gynecomastia is a benign breast enlargement in males that affects approximately one-third of adolescents. The exact mechanism is not fully understood; however, it has been proposed that estrogen receptors and aromatase enzyme activity may play important roles in the pathogenesis of gynecomastia. While many studies have reported that aromatase enzyme (CYP19) gene polymorphism is associated with gynecomastia, only one study has shown a relationship between estrogen receptor (ER) alpha and beta gene polymorphism and gynecomastia. Thus, the aim of this study was to evaluate the relationships between CYP19 (rs2414096), ER alpha (rs2234693), ER beta (rs4986938), leptin (rs7799039), and leptin receptor (rs1137101) gene polymorphisms and gynecomastia. METHODS: This study included 107 male adolescents with gynecomastia and 97 controls. Total serum testosterone (T) and estradiol (E2) levels were measured, and DNA was extracted from whole blood using the PCR-RFLP technique. The polymorphic distributions of CYP19, ER alpha, ER beta, leptin and leptin receptor genes were compared. RESULTS: The median E2 level was 12.41 (5.00-65.40) pg/ml in the control group and 16.86 (2.58-78.47) pg/ml in the study group (p<0.001). The median T level was 2.19 (0.04-7.04) ng/ml in the control group and 1.46 (0.13-12.02) ng/ml in the study group (p=0.714). There was a significant relationship between gynecomastia and leptin receptor rs1137101 (p=0.002) and ER beta receptor rs4986938 gene polymorphisms (p=0.002). CONCLUSIONS: According to our results, increased E2 level and ER beta gene rs4986938 polymorphism might explain why some adolescents have gynecomastia. Leptin receptor gene rs1137101 polymorphism might affect susceptibility to gynecomastia.

Sirtuin gene polymorphisms are associated with chronic obstructive pulmonary disease in patients in Mugla province.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an irreversible progressive chronic inflammatory disease that causes shortness of breath in consequence of a decrease in pulmonary functions. The pulmonary inflammatory pathogenesis is multifactorial. We have too little up-to-date information about the relation between COPD and genetics. In our study, the relation with the SIRT1 gene's mononucleotide polymorphisms (SNP) rs7895833, rs7069102 and rs2273773 was analyzed through various laboratory data. MATERIAL AND METHODS: One hundred COPD patients from the archive records of the Chest Diseases Department of Mugla Sitki Kocman University Medical Faculty were included in the study. A control group was constituted from 100 healthy individuals who live in the same geographical region. The SIRT1 genotypes for these patients were determined using polymerase chain reaction (PCR) and confronting two-pair primers (CTPP) methods. The SIRT1 gene polymorphisms rs7895833, rs7069102 and rs2273773 were analyzed. GG, AG, AA genotypes and G and A alleles of rs7895833, TT, TC, CC genotypes and T and C alleles of rs2273773, and CC, CG, GG genotypes and C and G alleles of rs7069102 were examined. The data in both groups were compared. CONCLUSIONS: A significant difference between GG, AG and AA genotypes of rs7895833 was found. Especially, the AG genotype was observed more in the group with COPD, with a significant difference. A significant difference between TT, TC and CC genotypes of rs2273773 was found. There was a significant difference between two groups with regards to C and G alleles of rs7069102. A significant difference was not found between the groups with regards to G and A alleles of rs7895833. A difference was not found for both groups between T and C alleles of rs2273773. It shows that these polymorphisms of the SIRT1 gene may be associated with COPD.

Genetic variants of synaptic vesicle and presynaptic plasma membrane proteins in idiopathic generalized epilepsy.

BACKGROUND: The aim of this study was to analyze the role of the genetic variants of two synaptic vesicle proteins (VAMP2 and Synaptotagmin XI) and two presynaptic plasma membrane proteins (Syntaxin 1A and SNAP-25) in patients with idiopathic generalized epilepsy (IGE). METHOD: Eighty-five patients with IGE and 93 healthy subjects were included in the study. We analyzed the functional polymorphisms of VAMP2, Synaptotagmin XI, Syntaxin 1A and SNAP-25 genes with polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: In the patients with IGE, significant differences alleles and genotypes of 26 bp Ins/Del polymorphism of the VAMP2 gene and the 33-bp promoter region of Synaptotagmin XI were observed, however no associaton was found regarding Intron 7 rs1569061 of Syntaxin 1A gene, MnlI rs3746544 and DdeI rs1051312 polymorphisms of SNAP-25 gene compared with healthy subjects. Carriers of the C allele of Synaptotagmin XI had worse measures compared with the T allele of Synaptotagmin XI. In the haplotype analysis, the frequency of the T alleles of rs1569061 and of the C alleles of the 33-bp promoter region of Synaptotagmin XI was found to be significantly higher in patients with IGE as compared with the healthy subjects. CONCLUSION: The genetic variations of VAMP2, Synaptotagmin XI might be indication of the relationship between these genes and IGE.

Chromosomal Translocation t (10;19) (q11.2;q13.4) in an Infertile Male.

Chromosomal rearrangements are usually associated with male factor infertility. We report here a 34-year-old man suffering from primary infertility for 15 years. The cytogenetic analysis and investigation of Y-chromosome microdeletions were performed. A reciprocal balanced translocation t (10;19) (q11.2;q13.4) was found in oligozoospermic infertile men with no Y-chromosome microdeletions. In this case, we aimed to evaluate the 46,XY,t (10;19) (q11.2;q13.4) karyo-type, which was detected through a cytogenetic analysis of a person referred to our genetic laboratory due to primary infertility, in the light of the literature.