The Induction of Oxidative/Nitrosative Stress, Inflammation, and Apoptosis by a Ferric Carboxymaltose Copy Compared to Iron Sucrose in a Non-Clinical Model

Introduction: Ferric carboxymaltose is a next-generation polynuclear iron(III)-hydroxide carbohydrate complex for intravenous iron therapy belonging to the class of so-called non-biological complex drugs. The product characteristics and therapeutic performance of non-biological complex drugs are largely defined by the manufacturing process. A follow-on product, termed herein as ferric carboxymaltose similar, is available in India. Given that non-biological complex drugs may display differences in diverse product properties not characterisable by physico-chemical methods alone. Aim: The aim is to assess the effects of this ferric carboxymaltose similar in our non-clinical model in non-anaemic healthy rats. Materials and Methods: Non-anaemic rats were treated with intravenous ferric carboxymaltose similar or iron sucrose both at (40 mg iron/kg body weight), or with saline solution (control) for four weeks, after which the animals were sacrificed. Parameters for tissue iron distribution, oxidative stress, nitrosative stress, inflammation and apoptosis were assessed by immunohistomorphometry. Results: Ferric carboxymaltose similar resulted in deranged iron distribution versus iron sucrose originator as indicated by increased serum iron, transferrin saturation and tissue iron(III) deposits as well as decreased ferritin deposits in the liver, heart and kidneys versus iron sucrose originator. Ferric carboxymaltose similar also increased significantly oxidative/nitrosative stress, pro-inflammatory, and apoptosis markers in the liver, heart and kidneys versus iron sucrose originator. Conclusion: In our rat model, ferric carboxymaltose similar had a less favourable safety profile than iron sucrose originator, adversely affecting iron deposition, oxidative and nitrosative stress, inflammatory responses, with impaired liver and kidney function.Fil: Toblli, Jorge Eduardo. Hospital Alemán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cao, Gabriel Fernando. Hospital Alemán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Angerosa, Margarita. Hospital Alemán; Argentin

Relationships between volatile compounds and sensory characteristics in virgin olive oil by analytical and chemometric approaches

BACKGROUND: The volatile fraction of virgin olive oil is characterised by low molecular weight compounds that vaporise at room temperature. In order to obtain an aroma profile similar to natural olfactory perception, the composition of the volatile compounds was determined by applying dynamic headspace gas chromatography, performed at room temperature, with a cryogenic trap directly connected to a gas chromatograph\u2013mass spectrometer system. Samples were also evaluated according to European Union and International Olive Council official methods for sensory evaluation. In this paper, the composition of the volatile fraction of 25 extra virgin olive oils fromdifferent regions of Italywas analysed and some preliminary considerations on relationships between chemical composition of volatile fraction and sensory characteristics are reported. RESULTS: Forty-two compounds were identified bymeans of the particular analytical technique used. All the analysed samples, classified as extra virgin by the panel test, never present peaks whose magnitude is important enough in defected oils. The study was focused on the evaluation of volatile compounds responsible for the positive impact on olive odour properties (\u2018green\u2013fruity\u2019 and \u2018sweet\u2019) and olfactory perception. CONCLUSION: Chemometric evaluation of data, obtained through headspace analysis and the panel test evaluation, showed a correlation between chemical compounds and sensory properties. On the basis of the results, the positive attributes of virgin olive oil are divided into two separated groups: sweet types or green types. Sixteen volatile compounds with known positive impact on odour properties were extracted and identified. In particular, eight compounds seem correlated with sweet properties whereas the green sensation appears to be correlated with eight other different substances. The content of the compounds at six carbon atoms proves to be very important in defining positive attributes of extra virgin olive oils and sensory evaluation

Influencia de la infestación por Dacus Oleae sobre el flavor de aceites, extraídos de aceitunas atacadas, por análisis HPLC y HRGC de compuestos volátiles

The authors have examined the influence of the Dacus Oleae infestation on the aroma of the oils obtained from olives of Coratina and Nebbio varieties at different levels of attack. The results obtained indicated a worsening of the qualitative level of the oils obtained from increasing percentages of infested olives; these were found to have a great decrease of phenolic substances and higher contents of both volatile alcohols and aldehydes with an unpleasant sensation. Of particular interest was hexanal/total volatile alcohols ratio, in which having been well correlated with the extent of infestation, would permit one to establish in an objective manner, if and how much the olives from which an oil has been extracted have suffered a Dacus attack.Los autores han examinado la influencia de la infestación por Dacus Oleae sobre el aroma de aceites obtenidos de aceitunas de las variedades Coratina y Nebbio en diferentes estados de ataque. Los resultados obtenidos indicaron un empeoramiento de los niveles de calidad de los aceites obtenidos a medida que se incrementaba el porcentaje de aceitunas infestadas; mostrando una gran disminución de las sustancias fenólicas y altos contenidos tanto de alcoholes volátiles como de aldehídos, con una sensación desagradable. De particular interés fue la relación hexanal/alcoholes volátiles totales, la cual ha sido bien correlacionada con la extensión de la infestación, lo que permitiría establecer de una manera objetiva, sí y cuantas de las aceitunas de las cuales se ha extraído, han sufrido ataque por Dacus

Comparison of early gastrointestinal tract and liver toxicity of the originator iron polymaltose complex (IPC) and an IPC similar preparation in non-anemic rats

Objectives: The originator iron polymaltose complex (Maltofer®, IPC, Vifor International, St. Gallen, Switzerland) has been used for over 30 years to treat iron deficiency anemia. Its physico-chemical properties allow for a controlled release of iron, a property which translates into low toxicity and good gastrointestinal (GI) tolerability of the drug compared to the commonly used ferrous salts. A variety of different iron polymaltose complex similars are commercially available with varying structures and, thus, different efficacy and toxicity compared to IPC. In this study, the median lethal dose, the GI tract and liver toxicity of an IPC similar (Vitalix®, IPCSVITA, Laboratorios Roemmers, Buenos Aires, Argentina) were compared with those of IPC in healthy rats. Methods: The median lethal dose of IPCSVITA was determined as the dose required to kill 6 out of 12 rats after 24 h from dosing. To compare the GI and liver toxicities, rats received IPCSVITA or IPC (both 280 mg iron/kg body weight) for 28 days. GI toxicity was assessed macroscopically by scoring lesion severities and microscopically by analyzing the villi/crypt ratio, number of eosinophils/villi and number of Goblet cells/villi. Ferritin was assessed in the small intestine villi and in the liver by immunostaining. Iron deposits in the liver were assessed by Prussian blue staining. Results: Serum iron concentration and transferrin saturation (TSAT) were significantly higher in the IPCSVITA group vs. the IPC and the control groups. Food consumption, body weight, and bowel movement at Day 29 were significantly lower within the IPCSVITA group vs. the IPC or the control groups. The lesion scores in the stomach and in the lower GI tract of the IPCSVITA group were significantly higher than those of the IPC and control groups. The villi/crypt ratio and the number of Goblet cells/villi in the small intestine were significantly lower in IPCSVITA-treated animals than in IPC-treated or control animals. The number of eosinophils per villi was significantly increased in the IPCSVITA group vs. IPC and control group. In the lower GI tract, microscopic lesions were observed only in the IPCSVITA group. The amount of ferritin in the small intestine and in the liver was higher in IPC-treated animals vs. IPCSVITA- treated or control animals. Conclusions: Higher serum iron and TSAT levels, lesions in the stomach and lower GI tract suggest the presence of weakly bound iron on the surface of the IPCSVITA complex, which has different physico-chemical properties than IPC. The lower levels of iron deposits in the liver suggest that the iron from IPCSVITA is taken up in a less controlled way than from IPC, thus, potentially accumulating in the wrong cellular compartment.Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Angerosa, Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin

Efecto del ataque de la mosca (Bactrocera oleae) sobre la calidad y contenido en compuestos polifenolicos de aceites procedentes de aceitunas de la variedad Chemlal

The attack on olives by the pest Bactrocera oleae has been studied to determine its influence on the olive oil quality (free acidity, peroxide value, UV extinction, sensorial quality), the total polyphenol and the individual phenolic compounds. The Algerian chemlal olive variety was used in this work. Quantitative and qualitative analyses of phenolic compounds were performed using the colorimetric method and the GC coupled with mass spectrometry. The results demonstrated that the attack modified the quality of olive oil and confirmed the existence of hydrolytic and mostly oxidative processess which strongly reduced the amount of O-diphenolic compounds. The extent of modification was much greater when the olives were attacked and harvested at an advanced stage of maturity. Early harvesting could be an effective way to limit the damage caused by B. oleae and to improve the quality of virgin olive oil.Se ha estudiado el ataque de las aceitunas por la plaga Bactrocera oleae con el fin de determinar la influencia sobre la calidad del aceite de oliva (acidez libre, índice de peróxidos, extinción UV, calidad sensorial), polifenoles totales e individuales. Este estudio se realizó con el aceite de oliva obtenido a partir de la mayoritaria variedad de Argelia (Chemlal). El análisis cuantitativo y cualitativo de los compuestos fenólicos se realizó por el método colorimétrico y por cromatografía gaseosa acoplada a la espectomertria de masas respectivamente. Los resultados demostraron que el ataque de la mosca, modifica la calidad del aceite de oliva y se confirmó además la existencia de procesos hidroliticos y, en particular oxidativos, que reducen fuertemente la cantidad de compuestos O-difenólicos. El alcance de la modificación fue mucho mayor cuando las aceitunas fueron atacadas en una fase avanzada de maduración. La recolección temprana podría ser una manera eficaz para limitar el daño causado por B. oleae y mejorar la calidad del aceite de oliva virgen y preservar los compuestos fenólicos

Comparison of Oxidative Stress and Inflammation Induced by Different Intravenous Iron Sucrose Similar Preparations in a Rat Model

Iron sucrose originator (ISORIG) has been used to treat iron deficiency and iron deficiency anemia for decades. Iron sucrose similars (ISSs) have recently entered the market. In this non-clinical study of non-anemic rats, five doses (40 mg iron/kg body weight) of six ISSs marketed in Asian countries, ISORIG or saline solution (control) were administered intravenously over four weeks to compare their toxicologic effects. Vasodilatory effects, impaired renal function and hepatic damage were only observed in the ISS groups. Significantly elevated serum iron and transferrin saturation levels were observed in the ISS groups suggesting a higher release of iron resulting in higher amounts of non-transferrin bound (free) iron compared to ISORIG. This might explain the elevated oxidative stress and increased levels of inflammatory markers and antioxidant enzymes in the liver, heart and kidneys of ISS-treated animals. Physico-chemical analyses showed that the molecular structure of most of the ISSs differed greatly from that of the ISORIG. These differences may be responsible for the organ damage and oxidative stress observed in the ISS groups. Significant differences were also found between different lots of a single ISS product. In contrast, polarographic analyses of three different ISORIG lots were identical, indicating that the molecular structure and thus the manufacturing process for ISORIG is highly consistent. Data from this study suggest that ISSs and ISORIG differ significantly. Therefore, before widespread use of these products it would be prudent to evaluate additional non-clinical and/or clinical data proving the safety, therapeutic equivalence and interchangeability of ISSs with ISORIG

Effects of iron deficiency anemia and its treatment with iron polymaltose complex in pregnant rats, their fetuses and placentas: Oxidative stress markers and pregnancy outcome

Objective: Iron deficiency anemia (IDA) can severely impair the outcome of pregnancy. IDA has been shown to cause oxidative stress, which may be exacerbated by oral iron therapy. In this study, the effects of IDA and its treatment with iron polymaltose complex/folic acid (IPC/FA) were examined in anemic pregnant rats, their fetuses and placentas. Study design: Hematological variables and oxidative stress markers in the liver, heart and kidney were evaluated in non-anemic, anemic and IPC/FA-treated pregnant rats and their fetuses. Markers for oxidative stress, inflammation and hypoxia were assessed in the placentas of all groups. Results: IDA was shown to increase oxidative stress levels in all the studied organs and in placenta as well as hypoxia and inflammation in placenta. IPC/FA treatment corrected IDA measured by the hemoglobin level, serum iron level and transferrin saturation. The oxidative stress levels in all the studied organs and in placentas of the IPC/FA-treated group were comparable to those of the non-anemic group. The number of fetuses and the neonatal and placental weight were lower in the anemic group compared to the non-anemic and IPC/FA-treated groups. Conclusions: The current study shows that IDA in pregnant rats impaired pregnancy outcome, increased the expression of hypoxia and inflammatory markers in the placenta, and increased oxidative stress in dams, fetuses and placentas. Treatment with oral IPC/FA corrected the IDA as well as reduced the levels of oxidative stress and inflammatory markers close to non-anemic control values in all the studied organs.Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Hospital Alemán; ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Hospital Alemán; ArgentinaFil: Oliveri, L.. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Hospital Alemán; ArgentinaFil: Angerosa, M.. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Hospital Alemán; Argentin

Evaluation of toxicity and oxidative stress induced by intravenous iron isomaltoside 1000 in a nonclinical model

The physicochemical characteristics of intravenous iron complexes affect the extent of weakly-bound iron and thus the degree of oxidative stress. The new preparation iron isomaltoside 1000 (IIM) was compared to iron sucrose (IS) and a control group in terms of biochemistry, oxidative stress, inflammatory markers and iron deposition in the liver, heart and kidneys of healthy rats. Renal function was significantly impaired in the IIM group versus both IS and controls. Liver enzymes were also significantly higher in IIM-treated animals versus the other groups, indicative of hepatic injury. Systolic blood pressure was significantly lower following IIM administration compared to IS or control animals. Oxidative stress in the liver, heart and kidneys was greater in the IIM group, as indicated by significantly increased levels of malondialdehyde and antioxidant enzyme activity, accompanied by a significantly lower ratio of reduced to oxidized glutathione. Microscopy demonstrated more extensive positive staining for iron, and a smaller area of ferritin staining, in the liver, heart and kidneys of rats treated with IIM versus IS. Levels of the inflammatory markers TNF-α and IL6 were both significantly higher in the IIM group versus IS in all assessed tissues. These findings indicate that IIM has a less favorable safety profile than IS in healthy rats, adversely affecting iron deposition, oxidative stress and inflammatory responses, with impaired liver and renal function.Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Oliveri, Leda María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Angerosa, Margarita. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentin