Citrus sinensis and Vitis vinifera Protect Cardiomyocytes from Doxorubicin-Induced Oxidative Stress: Evaluation of Onconutraceutical Potential of Vegetable Smoothies

The interest towards nutraceuticals able to counteract drug side effects is continuously growing in current chemotherapeutic protocols. In the present study, we demonstrated that smoothies containing mixtures of Citrus sinensis and Vitis vinifera L. cv. Aglianico N, two typical fruits of the Mediterranean diet, possess bioactive polyphenols that protect cardiomyocytes against doxorubicin-induced oxidative stress. The polyphenolic extracts isolated from Citrus sinensis- and Vitis vinifera-based functional smoothies were deeply characterized by Liquid Chromatography-Mass Spectrometry methods. Subsequently, the functional smoothies and relative mixtures were tested to verify their ability to affect cellular viability and oxidative stress parameters in embryonic cardiomyocyte cells (H9c2), and human breast adenocarcinoma cell line (MCF-7) exposed to doxorubicin. Interestingly, we found that the mix resulting from Citrus sinensis and Vitis vinifera association in ratio 1:1 was able to reduce cardiomyocytes damage induced by anthracyclines, without significantly interfering with the pro-apoptotic activity of the drug on breast cancer cells. These results point out the potential use of vegetable smoothies as adjuvants functional foods for chemotherapeutic anticancer protocols

Potential Role of Natural Antioxidant Products in Oncological Diseases

Nutrition has a significant effect and a crucial role in disease prevention. Low consumption of fruit and vegetables and a sedentary lifestyle are closely related with the onset and development of many types of cancer. Recently, nutraceuticals have gained much attention in cancer research due to their pleiotropic effects and relatively non-toxic behavior. In fact, although in the past there have been conflicting results on the role of some antioxidant compounds as allies against cancer, numerous recent clinical studies highlight the efficacy of dietary phytochemicals in the prevention and treatment of cancer. However, further investigation is necessary to gain a deeper understanding of the potential anticancer capacities of dietary phytochemicals as well as the mechanisms of their action. Therefore, this review examined the current literature on the key properties of the bioactive components present in the diet, such as carotenoids, polyphenols, and antioxidant compounds, as well as their use in cancer therapy. The review focused on potential chemopreventive properties, evaluating their synergistic effects with anticancer drugs and, consequently, the side effects associated with current cancer treatments

. Evaluation of the antioxidant and antiproliferative potential properties of phytocomplexes extracted from Mediterranean area fruits

Breast and cervical cancer represents the first and the second cause of death for women worldwide1,2. Therefore, new advanced chemotherapies applications are very urgently needed this cancer. High attention has been paid to natural compounds in fruits and vegetables with potential nutraceutical properties. In this regard, dietary polyphenols have been widely demonstrated to be able to not only reduce oxidative and inflammatory stress, but also decrease proliferation of cancer cells. However, the biological activity of various food plants has not yet been studied. This work aims to characterize the nutraceutical potential of four fruits such as, Malpighia emarginata (MEE), Arbutus unedo (AUE), Goji berries (LBE), Annona cherimola (ACE). For this reason, our study focused on the evaluation of antioxidant potential and antiproliferative activity of polyphenol extracts on cervical cancer (HeLa) and breast cancer (MCF-7) cell line

Standardized Duplex Ultrasound-Based Protocol for Early Diagnosis of Transplant Renal Artery Stenosis: Results of a Single-Institution Retrospective Cohort Study

Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after kidney transplantation (KT) and has been associated with potentially reversible refractory hypertension, graft dysfunction, and reduced patient survival. The aim of the study is to describe the outcomes of a standardized Duplex Ultrasound- (DU-) based screening protocol for early diagnosis of TRAS and for selection of patients potentially requiring endovascular intervention. We retrospectively reviewed our prospectively collected database of KT from January 1998 to select patients diagnosed with TRAS. The follow-up protocol was based on a risk-adapted, dynamic subdivision of eligible KT patients in different risk categories (RC) with different protocol strategies (PS). Of 598 patients included in the study, 52 (9%) patients had hemodynamically significant TRAS and underwent percutaneous angioplasty (PTA) and stent placement. Technical and clinical success rates were 97% and 90%, respectively. 7 cases of restenosis were recorded at follow-up and treated with re-PTA plus stenting. Both DU imaging and clinical parameters improved after stent placement. Prospective high-quality studies are needed to test the efficacy and safety of our protocol in larger series. Accurate trial design and standardized reporting of patient outcomes will be key to address the current clinical needs

Chemical constituents of Ulmus minor subsp. minor fruits used in the Italian phytoalimurgic tradition and their anti-inflammatory activity evaluation

: The phytochemical investigation of Ulmus minor subsp. minor samaras EtOAc and n-BuOH extracts is reported in this work for the first time, resulting in the isolation and characterization of twenty compounds (1: -20: ) including one new flavan-3-ol (1: ), one new trihydroxy fatty acid (2: ), and two glycosylated flavonoids (6: -7: ) whose NMR data are not available in the literature. Structure elucidation of the isolated compounds was obtained by 1D and 2D NMR and HRESIMS data. Prior to further pharmacological investigations, the extracts (100-6.25 µg/mL) and compounds 1: -12: (50-5 µM) were tested for their influence on viability of a murine macrophage cell line (J774A.1). Subsequently, extracts and compounds that did not impede viability were studied for their inhibitory effect on some mediators of inflammation in J774A.1 cells stimulated with lipopolysaccharide of Escherichia coli (LPS). The NO release and the expression of iNOS and COX-2 were then evaluated and both extracts (50-6.25 µg/mL) and compounds (20-5 µM) significantly inhibited NO release as well as iNOS and COX-2 expression in macrophages. These data highlight the anti-inflammatory properties of several isolated compounds from U. minor samaras supporting its possible alimentary use

Inflammatory mediators in a short-time mouse model of doxorubicin-induced cardiotoxicity

Doxorubicin (DOXO) is commonly used to treat a wide range of malignant tumors, but its clinical use is limited by acute and chronic cardiotoxicity. The precise mechanism underlying DOXO-induced cardiotoxicity is still not completely elucidated, but cardiac inflammation seems to be involved. Effects of DOXO on proinflammatory cytokines, inflammatory cell infiltration, and necrosis have been proven only when a functional impairment has already occurred, so this study aimed to investigate the acute effect of DOXO administration in mouse heart. The results of our study demonstrated alterations in cardiac function parameters assessed by ultrasound within 24h after a single injection of DOXO, with a cumulative effect along the increase of the dose and the number of DOXO administrations. At the same time, DOXO causes a significant production of proinflammatory cytokines (such as TNF-α and IL-6) with a concomitant reduction of IL-10, a well-known antiinflammatory cytokine. Furthermore, overexpression of inducible nitric oxide synthase (iNOS) in heart tissue and increased levels of serum nitrite in DOXO-treated mice were detected. Notably, DOXO administration significantly increased nitrotyrosine expression in mouse heart. Our data support the hypothesis that these early events, could be responsible for the later onset of more severe deleterious remodeling leading to DOXO induced cardiomyopathy

Anti-inflammatory properties of polyphenolic extract from green lettuce (Lactuca sativa L.; var. Maravilla de Verano) and fast analytical characterization

Several observation highlight the importance of a balanced diet to maintain and improve the health status. In this regard the consumption of fruits and vegetables is associated to a lower onset of several diseases. This is related to the presence of bioactive phytochemicals in these matrices, such as polyphenols. In this research we report the anti-inflammatory and antioxidant potential of polyphenols extracted from lettuce (var. Maravilla de Verano), in J774A.1 macrophages stimulated withEscherichia coli lipopolysaccharide (LPS)[1]. Lettuce extract significantly decreased reactive oxygenspecies, nitric oxide release, inducible nitric oxide synthase and cycloxygenase-2 expression. Moreover the quali/quantitative polyphenolic content was described in detail by a fast liquid chromatography-mass spectrometry approach. Our result show the importance of the consumption of fresh-cut vegetables in daily die

UHPLC profiling and effects on LPS-stimulated J774A.1 macrophages of flavonoide from bergamot (Citrus bergamia) juice, an underestimed waste product with high anti-inflammatory potential

Despite its high content of flavonoids, bergamot (Citrus bergamia) juice, is considered a waste product of the essential oil industry. In the present contribution, the potential of bergamot juice against inflammation process is highlighted. After a fast and accurate characterization, by a novel UHPLC-IT-TOF platform, we evaluated the in vitro effect of bergamot juice against inflammatory response induced by Escherichia coli lipopolysaccharide (LPS) in J774A.1 murine macrophages. Bergamot juice reduced reactive oxygen species (ROS) release and other important pro-inflammatory mediators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2) protein expression. Moreover, the cytoprotective haem-oxygenase-1 (OH-1) enzyme expression in LPS-stimulated J774A.1 macrophages was enhanced. Our results demonstrated that bergamot juice acts as antioxidant and anti-inflammatory agent in LPS-treated J774A.1 macrophages

Cardiotoxic Effects of Short-Term Doxorubicin Administration: Involvement of Connexin 43 in Calcium Impairment

The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy. C57BL/6j female mice were randomly divided in groups and injected with DOXO (2 or 10 mg/kg i.p.) for 1–3 or 7 days once every other day. Cardiac function was assessed by Echocardiography. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCAII) and phospholamban (PLB) expression were assessed by Western blot analysis, intracellular [Ca2+] were detected spectrofluorometrically by means of Fura-2 pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and localization was analyzed by Western blot and confirmed by immunofluorescence analysis. DOXO induces impairment in Ca2+ homeostasis, already evident after a single administration, and affects Cx43 expression and localization. Our data suggest that DOXO-induced alterations in Ca2+ homeostasis causes in the cells the induction of compensatory mechanisms until a certain threshold, above which cardiac injury is triggered