The effect of hydro alcoholic extract of Nigella sativa seeds on inflammatory mediators in C6 glioma cell line.

SUBJECT: Nigella sativa (N. sativa) is a highly valued nutritional plant, which has long been used in traditional medicine to treat a variety of human diseases. The multifaceted pharmacological impacts of N. sativa, such as attenuating oxidative stress and inflammation, make it a suitable therapeutic candidate against cardiovascular, hepatic, and neurological disorders as well as cancer. Therefore, the current study aimed to evaluate the effect of the hydroalcoholic extract of N. sativa seeds on several pro-inflammatory cytokines in the C6 glioma cell line and to compare it with the effect of the extract on the normal fibroblast cell line. METHODS: C6 and fibroblast cell lines were treated with the extract of N. sativa seeds, and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine the half-maximal inhibitory concentration (IC50) after 72h of treatment. Real-time polymerase chain reaction (RT-PCR) was carried out to assess the expression levels of interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), and transforming growth factor- ß1 (TGF-ß1) at the mRNA level in both cell lines after 72h of treatment with non-toxic and IC50 concentrations obtained from C6 cell line. RESULTS: The IC50 values for the hydroalcoholic extract of N. sativa seeds were 260±20µg/mL in the C6 cell line and 398±27µg/mL in fibroblast cells. The real-time PCR results indicated that the treatment of C6 and fibroblast cells with the extract at the IC50 value of N. sativa in C6 for 72h could increase the mRNA expression levels of IL-10 and reduce the mRNA expression levels of IL-6, TNF-α, and TGF-ß1 in C6 and fibroblast cells. The N. sativa extract showed a higher anti-inflammatory effect on C6 cells in comparison with fibroblast cells. CONCLUSIONS: Regarding the anti-inflammatory effect of Nigella sativa in C6 cell line, it may be considered a promising candidate to fortify antitumor actions in combination with other therapeutic options in the treatment of patients with GBM.

Radiation-induced Non-targeted Effect and Carcinogenesis; Implications in Clinical Radiotherapy.

Bystander or non-targeted effect is known to be an interesting phenomenon in radiobiology. The genetic consequences of bystander effect on non-irradiated cells have shown that this phenomenon can be considered as one of the most important factors involved in secondary cancer after exposure to ionizing radiation. Every year, millions of people around the world undergo radiotherapy in order to cure different types of cancers. The most crucial aim of radiotherapy is to improve treatment efficiency by reducing early and late effects of exposure to clinical doses of radiation. Secondary cancer induction resulted from exposure to high doses of radiation during treatment can reduce the effectiveness of this modality for cancer treatment. The perception of carcinogenesis risk of bystander effects and factors involved in this phenomenon might help reduce secondary cancer incidence years after radiotherapy. Different modalities such as radiation LET, dose and dose rate, fractionation, types of tissue, gender of patients, etc. may be involved in carcinogenesis risk of bystander effects. Therefore, selecting an appropriate treatment modality may improve cost-effectiveness of radiation therapy as well as the quality of life in survived patients. In this review, we first focus on the carcinogenesis evidence of non-targeted effects in radiotherapy and then review physical and biological factors that may influence the risk of secondary cancer induced by this phenomenon.

Reduction-oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics

Every year, millions of cancer patients undergo radiation therapy for treating and destroying abnormal cell growths within normal cell environmental conditions. Thus, ionizing radiation can have positive therapeutic effects on cancer cells as well as post-detrimental effects on surrounding normal tissues. Previous studies in the past years have proposed that the reduction and oxidation metabolism in cells changes in response to ionizing radiation and has a key role in radiation toxicity to normal tissue. Free radicals generated from ionizing radiation result in upregulation of cyclooxygenases (COXs), nitric oxide synthase (NOSs), lipoxygenases (LOXs) as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and their effected changes in mitochondrial functions are markedly noticeable. Each of these enzymes is diversely expressed in multiple cells, tissues and organs in a specific manner. Overproduction of reactive oxygen radicals (ROS), reactive hydroxyl radical (ROH) and reactive nitrogen radicals (RNS) in multiple cellular environments in the affected nucleus, cell membranes, cytosol and mitochondria, and other organelles, can specifically affect the sensitive and modifying enzymes of the redox system and repair proteins that play a pivotal role in both early and late effects of radiation. In recent years, ionizing radiation has been known to affect the redox functions and metabolism of NADPH oxidases (NOXs) as well as having destabilizing and detrimental effects on directly and indirectly affected cells, tissues and organs. More noteworthy, chronic free radical production may continue for years, increasing the risk of carcinogenesis and other oxidative stress-driven degenerative diseases as well as pathologies, in addition to late effect complications of organ fibrosis. Hence, knowledge about the mechanisms of chronic oxidative damage and injury in affected cells, tissues and organs following exposure to ionizing radiation may help in the development of treatment and management strategies of complications associated with radiotherapy (RT) or radiation accident victims. Thus, this medically relevant phenomenon may lead to the discovery of potential antioxidants and inhibitors with promising results in targeting and modulating the ROS/NO-sensitive enzymes in irradiated tissues and organ injury systems

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Reduction-oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics.

Every year, millions of cancer patients undergo radiation therapy for treating and destroying abnormal cell growths within normal cell environmental conditions. Thus, ionizing radiation can have positive therapeutic effects on cancer cells as well as post-detrimental effects on surrounding normal tissues. Previous studies in the past years have proposed that the reduction and oxidation metabolism in cells changes in response to ionizing radiation and has a key role in radiation toxicity to normal tissue. Free radicals generated from ionizing radiation result in upregulation of cyclooxygenases (COXs), nitric oxide synthase (NOSs), lipoxygenases (LOXs) as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and their effected changes in mitochondrial functions are markedly noticeable. Each of these enzymes is diversely expressed in multiple cells, tissues and organs in a specific manner. Overproduction of reactive oxygen radicals (ROS), reactive hydroxyl radical (ROH) and reactive nitrogen radicals (RNS) in multiple cellular environments in the affected nucleus, cell membranes, cytosol and mitochondria, and other organelles, can specifically affect the sensitive and modifying enzymes of the redox system and repair proteins that play a pivotal role in both early and late effects of radiation. In recent years, ionizing radiation has been known to affect the redox functions and metabolism of NADPH oxidases (NOXs) as well as having destabilizing and detrimental effects on directly and indirectly affected cells, tissues and organs. More noteworthy, chronic free radical production may continue for years, increasing the risk of carcinogenesis and other oxidative stress-driven degenerative diseases as well as pathologies, in addition to late effect complications of organ fibrosis. Hence, knowledge about the mechanisms of chronic oxidative damage and injury in affected cells, tissues and organs following exposure to ionizing radiation may help in the development of treatment and management strategies of complications associated with radiotherapy (RT) or radiation accident victims. Thus, this medically relevant phenomenon may lead to the discovery of potential antioxidants and inhibitors with promising results in targeting and modulating the ROS/NO-sensitive enzymes in irradiated tissues and organ injury systems.