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Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy
Get PDFCancer is the second cause of death worldwide. Chemotherapy and radiotherapy are the most common modalities for the treatment of cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance and the incidence of several side effects following both chemotherapy and radiotherapy. Inflammation resulting from radiotherapy and chemotherapy is responsible for adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, and bone marrow toxicity. Chronic inflammation may also lead to the development of second cancer during years after treatment. A number of anti-inflammatory drugs such as nonsteroidal anti-inflammatory agents have been proposed to alleviate chronic inflammatory reactions after radiotherapy or chemotherapy. Curcumin is a well-documented herbal anti-inflammatory agents. Studies have proposed that curcumin can help management of inflammation during and after radiotherapy and chemotherapy. Curcumin targets various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor κB (NF-κB), thereby attenuating the release of proinflammatory and profibrotic cytokines, and suppressing chronic production of free radicals, which culminates in the amelioration of tissue toxicity. Through modulation of NF-κB and its downstream signaling cascade, curcumin can also reduce angiogenesis, tumor growth, and metastasis. Low toxicity of curcumin is linked to its cytoprotective effects in normal tissues. This protective action along with the capacity of this phytochemical to sensitize tumor cells to radiotherapy and chemotherapy makes it a potential candidate for use as an adjuvant in cancer therapy. There is also evidence from clinical trials suggesting the potential utility of curcumin for acute inflammatory reactions during radiotherapy such as dermatitis and mucositis. © 2018 Wiley Periodicals, Inc
The impact of the particle size of curcumin nanocarriers and the ethanol on beta1-integrin overexpression in fibroblasts: A regenerative pharmaceutical approach in skin repair and anti-aging formulations
No full textBackground: Since women pay more attention to their skin�s health, pharmaceutical companies invest heavily on skin care product development. Further, the success of drug nano-carriers in passing through the skin justifies the need to conduct studies at the nano-scale. β1-integrin down regulation has been proposed as a sign of skin aging. Methods: Six drug nano-carriers (50 and 75 nm) were prepared at three ethanol concentrations (0, 3,and 5) and different temperatures. Then, the impact of Nanocarriers on fibroblasts were investigated. Results: DLS showed that increasing ethanol concentration decreased the surface tension that caused a decrease in the particle size in non-temperature formulations while increasing the temperature to 60 °C to lower Gibbs free energy increased the particle size. Ethanol addition decreased β1-integrin over-expression, whereas larger nano-carriers induced an over-expression of β1-integrin, Bcl2/Bax ratio, and an increase in live cell number. β1-integrin over-expression did not correlate with the rate of fibroblast proliferation and NFκB expression. An increase in fibroblast mortality in relation to smaller nano-carriers was not only due to the increase in Bax ratio, but was related to NFκB over-expression. Conclusion: The development of a regenerative pharmaceutical approach in skin repair was based on the effect of particle size and ethanol concentration of the drug nano-carriers on the expression of β1-integrin in fibroblasts. A curcumin nanoformulation sized 77 nm and containing of 3 ethanol was more effective in increasing β1-integrin gene over-expression, anti-apoptosis of fibroblast cells (Bcl2/Bax ratio), and in decreasing Bax and NFκB gene expression than that with a particle size of 50 nm. Such a formulation may be considered a valuable candidate in anti-aging and wound-healing formulations. Figure not available: see fulltext.. © 2019, Springer Nature Switzerland AG
NADPH oxidase as a target for modulation of radiation response; implications to carcinogenesis and radiotherapy
Get PDFBackground: Radiotherapy is a treatment modality for cancer. For better therapeutic efficiency, it could be used in combination with surgery, chemotherapy or immunotherapy. In addition to its beneficial therapeutic effects, exposure to radiation leads to several toxic effects on normal tissues. Also, it may induce some changes in genomic expression of tumor cells, thereby increasing the resistance of tumor cells. These changes lead to the appearance of some acute reactions in irradiated organs, increased risk of carcinogenesis, and reduction in the therapeutic effect of radiotherapy. Discussion: So far, several studies have proposed different targets such as cyclooxygenase-2 (COX-2), some toll-like receptors (TLRs), mitogen-activated protein kinases (MAPKs) etc., for the amelioration of radiation toxicity and enhancing tumor response. NADPH oxidase includes five NOX and two dual oxidases (DUOX1 and DUOX2) subfamilies that through the production of superoxide and hydrogen peroxide, play key roles in oxidative stress and several signaling pathways involved in early and late effects of ionizing radiation. Chronic ROS production by NOX enzymes can induce genomic instability, thereby increasing the risk of carcinogenesis. Also, these enzymes are able to induce cell death, especially through apoptosis and senescence that may affect tissue function. ROS-derived NADPH oxidase causes apoptosis in some organs such as intestine and tongue, which mediate inflammation. Furthermore, continuous ROS production stimulates fibrosis via stimulation of fibroblast differentiation and collagen deposition. Evidence has shown that in contrast to normal tissues, the NOX system induces tumor resistance to radiotherapy through some mechanisms such as induction of hypoxia, stimulation of proliferation, and activation of macrophages. However, there are some contradictory results. Inhibition of NADPH oxidase in experimental studies has shown promising results for both normal tissue protection and tumor sensitization to ionizing radiation. Conclusion: In this article, we aimed to review the role of different subfamilies of NADPH oxidase in radiation-induced early and late normal tissue toxicities in different organs. © 2019 Bentham Science Publishers
Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy
No full textCancer incidences are growing and cause millions of deaths worldwide. Cancer therapy is one of the most important challenges in medicine. Improving therapeutic outcomes from cancer therapy is necessary for increasing patients� survival and quality of life. Adjuvant therapy using various types of antibodies or immunomodulatory agents has suggested modulating tumor response. Resistance to apoptosis is the main reason for radioresistance and chemoresistance of most of the cancers, and also one of the pivotal targets for improving cancer therapy is the modulation of apoptosis signaling pathways. Apoptosis can be induced by intrinsic or extrinsic pathways via stimulation of several targets, such as membrane receptors of tumor necrosis factor-α and transforming growth factor-β, and also mitochondria. Curcumin is a naturally derived agent that induces apoptosis in a variety of different tumor cell lines. Curcumin also activates redox reactions within cells inducing reactive oxygen species (ROS) production that leads to the upregulation of apoptosis receptors on the tumor cell membrane. Curcumin can also upregulate the expression and activity of p53 that inhibits tumor cell proliferation and increases apoptosis. Furthermore, curcumin has a potent inhibitory effect on the activity of NF-κB and COX-2, which are involved in the overexpression of antiapoptosis genes such as Bcl-2. It can also attenuate the regulation of antiapoptosis PI3K signaling and increase the expression of MAPKs to induce endogenous production of ROS. In this paper, we aimed to review the molecular mechanisms of curcumin-induced apoptosis in cancer cells. This action of curcumin could be applicable for use as an adjuvant in combination with other modalities of cancer therapy including radiotherapy and chemotherapy. © 2019 Wiley Periodicals, Inc
Melatonin is a potential inhibitor of ovarian cancer: Molecular aspects
Get PDFOvarian cancer is one of the most common causes of morbidity related to gynecologic malignancies. Possible risk factors are including hereditary ovarian cancer, obesity, diabetes mellitus, alcohol consumption, aging, and smoking. Various molecular signaling pathways including inflammation, oxidative stress, apoptosis and angiogenesis are involved in this progression of ovarian cancer. Standard treatments for recently diagnosed patients are Surgery and chemotherapy such as co-treatment with other drugs such that the exploitation of neoadjuvant chemotherapy is expanding. Melatonin (N-acetyl-5-methoxy-tryptamine), an endogenous agent secreted from the pineal gland, has anti-carcinogenic features, such as regulation of estradiol production, cell cycle modulation, stimulation of apoptosis as well as anti-angiogenetic properties, anti-inflammatory activities, significant antioxidant effects and modulation of various immune system cells and cytokines. Multiple studies have shown the significant beneficial roles of melatonin in various types of cancers including ovarian cancer. This paper aims to shed light on the roles of melatonin in ovarian cancer treatment from the standpoint of the molecular aspects. © 2019 The Author(s)
Tempol improves oxidant/antioxidant parameters in testicular tissues of diabetic rats
Get PDFAims: Oxidative stress induced by diabetes mellitus (DM) is considered as one of the main causes of infertility in diabetic patients. The aim of the present study was to assess the effect of Tempol � as a synthetic antioxidant- on the testis oxidative stress and sperm parameters in type 2 diabetic (T2D) rats. Main methods: Twenty male Wistar rats were divided into 4 groups. Control groups (C) and diabetic groups (D); the control and diabetic groups received Tempol (100 mg/kg) for one month. Sperm parameters and oxidative stress biomarkers were evaluated in testicular tissue. Key findings: The results demonstrated that administration of Tempol in diabetic rats improved sperm motility and viability and decreased the count of abnormal sperms. Also Tempol decreased the fasting blood sugar (FBS) and lipid peroxidation (LPO). In addition, Tempol significantly increased total antioxidant capacity (TAC) levels in testis tissue of T2D rats. Histopathological changes were also improved in the diabetic treated group. Significance: Taken together, the results indicated that Tempol improved fertility parameters in a diabetic rat through reducing oxidative stress. © 2019 Elsevier Inc
Factor structure and reliability of the mindfulness attention awareness scale for adolescents and the relationship between mindfulness and anxiety in adolescents
Get PDFBackground: In recent years, application and practice of mindfulness-based interventions to reduce adolescent psychological problems are increasing. Therefore, it is necessary to design and study tools that measure mindfulness and its effects. Objectives: One of the available tools to measure mindfulness in adolescents is the mindfulness attention awareness scale for adolescents (MAAS-A). The current study aimed at examining the factor structure and reliability of a Persian version of this scale and investigating the relationship between mindfulness and anxiety. Methods: The current descriptive, cross sectional and psychometric study was conducted on 354 students from Kashan city, Iran, selected via the cluster sampling method in 2017. The exploratory factor analysis (EFA) by the principle component analysis method, the confirmatory factor analysis (CFA), and the relationship between mindfulness and anxiety were conducted to examine the validity of the MAAS-A. To calculate the reliability of the MAAS-A, Cronbach's alpha and test-retest reliability (four-week interval) were employed. The statistical analysis was performed with SPSS version 19.0 and AMOS-22. Results: The results of the EFA suggested two factors for this scale labeled as �acting with attention and awareness� and �attention to the present moment�. The CFA confirmed the two-factor model of the 14-item scale (the root mean square error of approximation (RMSEA) 90 confidence interval (CI) = 0.001 - 0.06). The reliability of this scale was good (α = 0.81, retest reliability = 0.86) and the correlation between mindfulness and anxiety was negative and significant (r = -0.43, P < 0.01). Also, this relationship was significant in females (r = -0.44, P < 0.01) and males (r = -0.46, P < 0.01). Conclusions: According to the results of the current study, the MAAS-A was a reliable and valuable scale to measure the mindfulness of adolescents. The results of correlation between mindfulness and anxiety meant that by increasing mindfulness, the anxiety reduced in adolescents. ©2018, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International Licens
The Effect of Magnesium and Vitamin e Co-Supplementation on Glycemic Control and Markers of Cardio-Metabolic Risk in Women with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial
No full textData on the effects of magnesium and vitamin E co-supplementation on glycemic control and markers of cardio-metabolic risk of patients with polycystic ovary syndrome (PCOS) were collected. This investigation was conducted to evaluate the effects of magnesium and vitamin E co-supplementation on glycemic control and markers of cardio-metabolic risk in women with PCOS. This randomized, double-blind, placebo-controlled trial was carried out on 60 women with PCOS, aged 18-40 years old. Participants were randomly divided into two groups to receive 250 mg/day magnesium plus 400 mg/day vitamin E supplements or placebo (n=30 each group) for 12 weeks. Fasting blood samples were taken at baseline and after the 12-week intervention to quantify related variables. After the 12-week intervention, compared with the placebo, magnesium and vitamin E co-supplementation led to a significant reduction in serum insulin levels (-1.1±3.0 vs. +1.6±3.7 μIU/ml, p=0.003) and homeostatic model of assessment for insulin resistance (-0.2±0.7 vs. +0.4±0.9, p=0.002), and a significant increase in the quantitative insulin sensitivity check index (+0.01±0.01 vs. -0.009±0.02, p=0.003). Furthermore, magnesium plus vitamin E supplementation significantly decreased serum triglycerides (-15.0±24.4 vs. +6.7±22.2 mg/dl, p=0.001) and VLDL-cholesterol concentrations (-3.0±4.9 vs. +0.6±2.4 mg/dl, P=0.01) compared with the placebo. A trend toward a greater decrease in total cholesterol levels was observed in magnesium plus vitamin E group compared to placebo group (-7.0±32.6 vs. +8.1±26.6 mg/dl, p=0.05). In conclusion, magnesium and vitamin E co-supplementation for 12 weeks to PCOS women had beneficial effects on parameters of insulin metabolism and few markers of cardio-metabolic risk. © Georg Thieme Verlag KG Stuttgart - New York
Clinical trial of the effects of coenzyme q10 supplementation on biomarkers of inflammation and oxidative stress in diabetic hemodialysis patients
Get PDFBackground: The aim of the study was to determine the effects of coenzyme Q10 (CoQ10) supplementation on biomarkers of inflammation and oxidative stress among diabetic hemodialysis (HD) patients. Methods: Sixty diabetic HD patients participated in the randomized, double blind, placebo-controlled clinical trial. They were randomly assigned into two groups to intake either 60 mg CoQ10 supplements (n = 30) or placebo (n = 30) twice a day for 12 weeks. Results: After 12 weeks of intervention, CoQ10 supplementation significantly increased total antioxidant (TAC) (54.921 ± 26.437 vs. -126.781 ± 26.437, P < 0.001) and nitric oxide (NO) levels (4.121 ± 1.314 vs. -1.427 ± 1.314, P = 0.006) and decreased C-reactive protein (CRP) (-1.302 ± 0.583 vs. 0.345 ± 0.583, 0.042) levels compared with the placebo. We did not observe any significant effect of CoQ10 supplementation on malondialdehyde (MDA) and glutathione (GSH) levels compared with the placebo. Conclusions: Overall, our study showed that CoQ10 supplementation to diabetic HD patients for 12 weeks was associated with increased levels of TAC and NO levels and decreased level of high-sensitivity CRP (hs-CRP) levels, but did not have any beneficial effects on MDA and GSH. © 2019 International Journal of Preventive Medicine
Carnitine and chromium co-supplementation affects mental health, hormonal, inflammatory, genetic, and oxidative stress parameters in women with polycystic ovary syndrome
No full textObjective: The aim of this study was to evaluate the effect of the co-administration of carnitine and chromium on mental health, hormonal, inflammatory and genetic parameters in women with PCOS. Methods: This randomized, double-blinded, placebo-controlled clinical trial was conducted on 54 subjects, aged 18�40 years old. Subjects were randomly allocated to take either 1000 mg/d carnitine plus 200 µg/d chromium as chromium picolinate (n = 26) or placebo (n = 27) for 12 weeks. Results: Carnitine and chromium co-supplementation, compared with the placebo, significantly improved beck depression inventory (β � 0.84; 95 CI, �1.51, �0.17; p = 0.01), general health questionnaire scores (β � 1.13; 95 CI, �2.13, �0.14; p = 0.02) and depression anxiety and stress scale scores (β � 0.96; 95 CI, �0.78, �0.14; p = 0.02). Participants who received carnitine plus chromium supplements had significantly lower total testosterone (β � 0.15 ng/mL; 95 CI, �0.24, �0.06; p = 0.002), hirsutism (β � 0.48; 95 CI, �0.91, �0.06; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (β � 1.02 mg/L; 95 CI, �1.79, �0.25; p = 0.01), and malondialdehyde (MDA) levels (β � 0.38 µmol/L; 95 CI, �0.56, �0.20; p < 0.001), and higher total antioxidant capacity (TAC) levels (β 107.18 mmol/L; 95 CI, 44.24, 170.12; p = 0.001) compared with the placebo. Moreover, carnitine and chromium co-supplementation upregulated gene expression of interleukin-6 (IL-6) (p = 0.02) and tumor necrosis factor alpha (TNF-α) (p = 0.02) compared with the placebo. Conclusion: Overall, the co-administration of carnitine and chromium for 12 weeks to women with PCOS had beneficial effects on mental health parameters, serum total testosterone, mF-G scores, hs-CRP, TAC and MDA levels, and gene expression of IL-6 and TNF-α. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group