ABSTRACT
BACKGROUND: Radiotherapy is the most common regimen for treating human cancers; however, ionizing radiation (IR) has hazardous effects on metabolically active organs such as the liver. AIM: This study aimed to investigate the possible protective (prophylactic and therapeutic) action of taurine against liver damage induced by gamma irradiation at different time intervals as well as the mechanisms by which taurine could provide its potential amelioration actions. METHODS: In this study, 90 adult male rats (â¼150 g) were randomly divided into five groups. Group 1 is the control group, group 2 received an oral daily dose (500 mg/kg) of taurine for two weeks, group 3 was exposed to a whole-body single dose of γ-irradiation (6 Gy), and groups 4 and 5 received taurine before or after γ-irradiation, respectively. Six rats from each group were sacrificed after 1, 2, and 3 weeks. RESULTS: Over the period of the 3 weeks studied, there were significant increases in MDA, NO, TNF-α, and cytochrome-c levels and ALT, caspases-9 and -3 activities and significant decreases in GSH, SOD, CAT, and GPx in the irradiated group when compared with the relevant control. The liver of irradiated rats showed dilatation in the central and portal veins, edema, and degenerated hepatocytes. CONCLUSIONS: Taken together, IR caused maximum devastation in the liver 2 weeks after exposure as shown by elevation of the inflammatory and apoptotic markers and reducing the antioxidants. Taurine was able to alleviate the deleterious biochemical and histological effects whether given before or after IR. The magnitude of the observed protective effects was in both cases very similar.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Apoptosis/drug effects , Apoptosis/radiation effects , Gamma Rays/adverse effects , Liver/drug effects , Liver/radiation effects , Taurine/pharmacology , Animals , Biomarkers/metabolism , Liver/metabolism , Liver/pathology , Male , Oxidative Stress/drug effects , Rats , Rats, WistarABSTRACT
Placental growth factor (PlGF) is produced by tumor cells and stimulates tumor growth and metastasis in part by upregulation of hypoxia inducible factor HIF1α. Orchestration of tumor cell proliferation and migration involves oscillations of cytosolic Ca2+ activity ([Ca2+]i). The [Ca2+]i oscillations could be accomplished by triggering of intracellular Ca2+ release followed by store-operated Ca2+-entry (SOCE). Mechanisms accomplishing SOCE include the pore-forming ion channel unit Orai1 and its regulator STIM1. The present study explored whether PlGF influences the expression of Orai1 and STIM1, as well as SOCE and whether this effect impacts on HIF1α expression. To this end, ovary carcinoma cells were cultured for 24â¯h without and with PlGF (10â¯ng/ml). Orai1, STIM1 and HIF1α transcript levels were quantified utilizing RT-PCR and Orai1, STIM1 and HIF1α protein levels by Western blotting. [Ca2+]i was estimated from Fura-2-fluorescence and SOCE from increase of [Ca2+]i following Ca2+ re-addition after Ca2+-store depletion with extracellular Ca2+ removal and sarcoendoplasmatic Ca2+-ATPase (SERCA) inhibitor thapsigargin (1⯵M). As a result, exposure of ovary carcinoma cells to PlGF was followed by a significant increase of Orai1 as well as STIM1 transcript and protein levels. PlGF significantly increased store-operated Ca2+-entry following re-addition of extracellular Ca2+, an effect virtually abrogated by Orai1 inhibitor MRS1845 (10⯵M). PlGF further increased HIF1α transcript and protein levels, an effect again significantly blunted by MRS1845 (10⯵M). In conclusion, PlGF upregulates expression of both, Orai1 and STIM1 thus enhancing store-operated Ca2+-entry with subsequent upregulation of HIF1α.
Subject(s)
Calcium/metabolism , Neoplasm Proteins/genetics , ORAI1 Protein/genetics , Ovarian Neoplasms/genetics , Placenta Growth Factor/metabolism , Stromal Interaction Molecule 1/genetics , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Ovarian Neoplasms/metabolism , Up-RegulationABSTRACT
Exposure to ionizing radiation (IR) is inevitable since over 80% of total average exposure comes from natural sources. Brain is vulnerable to the deleterious effects of IR. Therefore, scientists paid attention in identifying novel compounds to protect against radiation-induced brain injury. Adult male albino rats weighing 120-150â¯g were divided into five groups, 18 rats each. Group 1 served as control, group 2 received an oral daily dose of taurine (500â¯mg/kg) for 2 weeks. Group 3 was exposed to a whole body single dose of γ-irradiation (6â¯Gy). Groups 4 and 5 received taurine before and after γ-irradiation, respectively. Six rats from each group were sacrificed after 1, 2 or 3 weeks. Throughout the 3 weeks studied, there were significant increases in MDA, NO, TNF-α levels, and Cytochrome-c and activities of Caspases -9 and -3 and significant decreases in GSH, SOD, CAT and GPx in the irradiated group when compared with the relevant control. Cerebral cortex of irradiated rats showed vacuolization and nuclear pyknosis in the neuronal cells and focal gliosis. Taurine administration pre- or post-irradiation significantly ameliorated all these previous effects. Taurine had antioxidant, anti-inflammatory, and anti-apoptotic effects and ameliorated the histopathological changes in brain in a time-dependent mode.