Leptin receptor gene (A/G) polymorphism rs1137101 and renal cell carcinoma.

Leptin plays an important role in carcinogenesis as leptin/leptin receptor signaling promotes the angiogenesis, proliferation, and inhibits epithelial cell apoptosis. Variants in the leptin receptor gene have potential associations with renal cell carcinoma (RCC). We aimed to investigate association of rs1137101 (A/G) polymorphism at LEPR gene with risk of RCC and patients survival. 123 individuals were classified into group I: 73 RCC patients and group II: 50 healthy controls. Genotyping of the Gln223Arg (A/G) polymorphism rs1137101 at LEPR gene was analyzed using allelic discrimination assay by Real-Time PCR technique. GG genotype was the most frequent among RCC patients (67.1%), while AA genotype was the most frequent in controls (60%); (p < 0.001). By univariate cox regression: gene polymorphism (GG versus GA +AA), stage, histopathologic subtype, and grade were found to affect survival significantly; however, the multivariate analysis showed that only gene polymorphism (GG versus GA +AA) and tumor stage significantly affect survival. LEPR gene variants rs1137101 might be a candidate risk factor for RCC in Egypt. GG genotype is associated with more aggressive tumor behavior and shorter survival compared with GA & AA genotypes so, genotyping of Gln223Arg (A/G) rs1137101 could also predict RCC outcome.

Phytotherapeutic effects of Echinacea purpurea in gamma-irradiated mice.

Echinacea (E.) purpurea herb is commonly known as the purple coneflower, red sunflower and rudbeckia. In this paper, we report the curative efficacy of an Echinacea extract in gamma-irradiated mice. E. purpurea was given to male mice that were divided into five groups (control, treated, irradiated, treated before irradiation & treated after irradiation) at a dose of 30 mg/kg body weight for 2 weeks before and after irradiation with 3 Gy of gamma-rays. The results reflected the detrimental reduction effects of gamma-rays on peripheral blood hemoglobin and the levels of red blood cells, differential white blood cells, and bone marrow cells. The thiobarbituric acid-reactive substances (TBARs) level, Superoxide dismutase (SOD) and glutathione peroxidase (GSPx) activities and DNA fragmentation were also investigated. FT-Raman spectroscopy was used to explore the structural changes in liver tissues. Significant changes were observed in the microenvironment of the major constituents, including tyrosine and protein secondary structures. E. purpurea administration significantly ameliorated all estimated parameters. The radio-protection effectiveness was similar to the radio-recovery curativeness in comparison to the control group in most of the tested parameters. The radio-protection efficiency was greater than the radio-recovery in hemoglobin level during the first two weeks, in lymphoid cell count and TBARs level at the fourth week and in SOD activity during the first two weeks, as compared to the levels of these parameters in the control group.

Protective role of hesperidin against γ-radiation-induced oxidative stress and apoptosis in rat testis.

BACKGROUND: Gamma (γ) ray, an electromagnetic radiation, is occasionally accompanying the emission of an alpha or beta particle. Exposure to such radiation can cause cellular changes such as mutations, chromosome aberration and cellular damage which depend upon the total amount of energy, duration of exposure and the dose. Ionizing radiation can impair spermatogenesis and can cause mutations in germ cells. In general, type B spermatogonia are sensitive to this type of radiation. The current study was carried out to evaluate the protective role of hesperidin (H), as a polyphenolic compound, on rat testis injury induced by γ-radiation. METHODS: Rats were divided into groups including C group (control rats), R (irradiated) group (rats irradiated with γ-radiation), Vehicle (V) group (rats administered with dimethylsulfoxide "DMSO"), H group (rats administered with H only), HR and RH groups (rats treated with H before and after exposure to γ-radiation, respectively). Malondialdehyde (MDA: the end product of lipid peroxidation "LPO") and xanthine oxidase (XO: it generates reactive oxygen species "ROS") in testes homogenate as well as nitric oxide (NO: as ROS) in mitochondrial matrix were determined. The apoptotic markers including DNA-fragmentation (DNAF) in testes homogenate and calcium ions (Ca2+) in mitochondrial matrix were determined. Superoxide dismutase (SOD) and catalase (CAT) activities in testes homogenate, while reduced glutathione "GSH" in nuclear matrix were determined. Also histopathological examination for testes tissues through electron microscope was studied. RESULTS: Exposure of rats to γ-radiation (R group) increased the levels of MDA, NO, DNAF, Ca2+ and XO activity, while it decreased GSH level, SOD and CAT activities as compared to the C groups; γ-radiation increased oxidative stress (OS), LPO, apoptosis and induced testes injuries. These results are in agreement with the histopathological examination. In contrast, treatment with H before or after exposure to γ-radiation (HR and RH groups, respectively) decreased the levels of MDA, NO, DNAF and Ca2+ but increased GSH level and the activities of SOD, CAT and XO as compared to R group and this indicates that H decreased OS, LPO and apoptosis. Also, the histopathological results showed that H improved testis architecture and this is related to the antioxidant and anti-apoptotic activities of H contents. Protection is more effective when H is given before rather than after exposure. Finally, administration of H to healthy rats for a short period had no adverse affect on testes cells. CONCLUSION: Hesperidin showed antioxidant and anti-apoptotic activities. It has a protective role against OS, injury and apoptosis induced by γ-radiation in testes. Protection is more effective when H is given before rather than after exposure.Graphical Abstract.

Vitamin E and selenium administration as a modulator of antioxidant defense system: biochemical assessment and modification.

Exposure of cells to ionizing radiation leads to the formation of reactive oxygen species (ROS) that are associated with radiation-induced cytotoxicity. Because of the serious damaging potential of ROS, cells depend on the elaboration of the antioxidant defense system (AODS), both enzymatic and nonenzymatic oxidant defense mechanisms. The deficiency in important components of the endogenous AODS leads to the accumulation of oxidative stress inducing oxidative damage. The antioxidant enzymes superoxide dismutase and glutathione peroxidase are key intracellular antioxidants in the metabolism of ROS. In the current study, we investigated the potential role of these antioxidant enzymes in radioresistance during the evaluation of the compensatory role of some exogenous micronutrients against oxidative stress Animals were categorized into eight groups, receiving vitamin E (alpha-tocopherol) and/or selenium (Se) with or without whole-body gamma-irradiation (6.5 Gy). The results indicate that antioxidant pretreatments before irradiation may have some beneficial effects against irradiation-induced injury. The results also indicate that selenium and vitamin E act alone and in an additive fashion as radioprotecting agents. The results further suggest that selenium confers protection in part by inducing or activating cellular free-radical scavenging systems and by enhancing peroxide breakdown, whereas vitamin E appears to confer its protection by an alternate complementary mechanism.

The effect of genetic polymorphisms in STIM1 and ORAI1 on erythropoietin resistance in Egyptian patients with end-stage renal disease.

Chronic renal failure (CRF) is an incurable disease with unique challenges. Anemia is a frequent complication affecting dialysis patients. Erythropoietin (EPO) is used to treat anemia, but a poor response may result. We investigated genetic polymorphisms of store-operated calcium channel (SOC) signaling, an important erythropoietin-activated pathway that may induce EPO resistance in patients with renal failure. A total of 108 end stage renal disease (ESRD) patients were selected for this study. Patients were divided into two groups according to their erythropoietin resistance index (ERI): 39 patients with an ERI>10 and 69 patients with an ERI<10. We selected four tagging single nucleotide polymorphisms (tSNPs) in STIM1 and five in ORAI1 in our study. A polymerase chain reaction was performed, and genotyping against EPO resistance was correlated. Patients with the AG genotype of rs1561876 in STIM1, the TC genotype of rs6486795 in ORAI1, and the TG or GG genotypes of rs12320939 in ORAI1 were associated with an increased risk of erythropoietin resistance. Overall, we reported a moderately significant relationship between genetic polymorphisms of STIM1 and EPO resistance. We also reported a highly significant relationship between genetic polymorphisms of ORAI1 and EPO resistance. The (A-A-G) haplotype of STIM1 and the (G-T-G-T-A, G-C-G-C-G, or G-T-T-C-G) haplotypes of ORAI1 were significantly associated with EPO resistance.