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Approaches to identify novel druggable targets for treating neglected diseases include computational studies that predict possible interactions of drugs and their molecular targets. Hypoxanthine phosphoribosyltransferase (HPRT) plays a central role in the purine salvage pathway. This enzyme is essential for the survival of the protozoan parasite T. cruzi, the causal agent of Chagas disease, and other parasites related to neglected diseases. Here we found dissimilar functional behaviours between TcHPRT and the human homologue, HsHPRT, in the presence of substrate analogues that can lie in differences in their oligomeric assemblies and structural features. To shed light on this issue, we carried out a comparative structural analysis between both enzymes. Our results show that HsHPRT is considerably more resistant to controlled proteolysis than TcHPRT. Moreover, we observed a variation in the length of two key loops depending on the structural arrangement of each protein (groups D1T1 and D1T1'). Such variations might be involved in inter-subunit communication or influencing the oligomeric state. Besides, to understand the molecular basis that govern D1T1 and D1T1' folding groups, we explored the distribution of charges on the interaction surfaces of TcHPRT and HsHPRT, respectively. To know whether the rigidity degree bears effect on the active site, we studied the flexibility of both proteins. The analysis performed here illuminates the underlying reasons and significance behind each protein's preference for one or the other quaternary arrangement that can be exploited for therapeutic approaches.

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Schistosomiasis is one of the most important human helminthiases worldwide. Praziquantel is the current treatment, and no vaccine is available until the present. Thus, the presented study aimed to evaluate the immunization effects with recombinant Schistosoma mansoni enzymes: Adenosine Kinase (AK) and Hypoxanthine-Guanine Phosphoribosyltransferase (HGPRT), as well as a MIX of the two enzymes. Female Balb/c mice were immunized in three doses, and 15 days after the last immunization, animals were infected with S. mansoni. Our results showed that the group MIX presented a reduction in the eggs in feces by 30.74% and 29%, respectively, in the adult worms. The groups AK, HGPRT and MIX could produce IgG1 antibodies, and the groups AK and MIX produced IgE antibodies anti-enzymes and anti-S. mansoni total proteins. The groups AK, HGPRT and MIX induced a reduction in the eosinophils in the peritoneal cavity. Besides, the group AK showed a decrease in the number of hepatic granulomas (41.81%) and the eggs present in the liver (42.30%). Therefore, it suggests that immunization with these enzymes can contribute to schistosomiasis control, as well as help to modulate experimental infection inducing a reduction of physiopathology in the disease.

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La hipoxantina y la xantina son biomarcadores metabólicos que resultan de la degradación de las proteínas purinas. Los análisis cienciométricos constituyen una herramienta para estudiar las publicaciones científicas en torno a un determinado tema con la finalidad de determinar tendencias en la literatura. Se realizó un análisis cienciométrico de la producción científica reciente sobre la hipoxantina y xantina en el ejercicio, publicada en la base de datos Scopus durante el período 2016 - 2021. Para la búsqueda en Scopus se utilizaron las palabras clave en idioma inglés: exercise, hypoxanthine y xanthine. Se realizó un análisis cuantitativo, tomando en cuenta los artículos encontrados, así como la información proporcionada por el software VOSviewer. Se identificaron 64 artículos, de estos, 56 fueron de investigación aplicada y ocho de revisión. La categoría de efecto del ejercicio tuvo una mayor cantidad de estudios con 23; dentro de esta se encuentra la subcategoría de metabolismo que presentó 21 artículos. Tanto Estados Unidos como Polonia son los países con mayor número de publicaciones. Existen distintos enfoques y protocolos de ejercicio utilizados para cuantificar la respuesta de la hipoxantina y xantina, así como los perfiles de los sujetos de estudio utilizados como muestra para las investigaciones. La cuantificación de hipoxantina y xantina en el cuerpo es importante para la investigación en el campo de las ciencias del ejercicio(AU)

Hypoxanthine and xanthine are metabolic biomarkers that result from the degradation of purine proteins. Scientometric analyzes constitute a tool to study scientific publications around a certain topic in order to determine trends in the literature. A scientometric analysis was carried out of the recent scientific production on hypoxanthine and xanthine in exercise, published in Scopus database during the period 2016-2021. For the search in Scopus, we used the English keywords exercise, hypoxanthine and xanthine. A quantitative analysis was carried out, taking into account the articles found, as well as the information provided by VOSviewer software. Sixty-four articles were identified, 56 of them were applied research and eight were review. The exercise effect category had a larger number of studies (23). Here there is a subcategory of metabolism that had 21 articles. The United States and Poland are both the countries with the highest number of publications. There are different approaches and exercise protocols used to quantify the response of hypoxanthine and xanthine, as well as the profiles of the study subjects used as a sample for the investigations. The quantification of hypoxanthine and xanthine in the body is important for research in the field of exercise science(AU)

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We have proposed that the abiogenesis of life around the beginning of the Archean may have been an example of "spontaneous" microscopic dissipative structuring of UV-C pigments under the prevailing surface ultraviolet solar spectrum. The thermodynamic function of these Archean pigments (the "fundamental molecules of life"), as for the visible pigments of today, was to dissipate the incident solar light into heat. We have previously described the non-equilibrium thermodynamics and the photochemical mechanisms which may have been involved in the dissipative structuring of the purines adenine and hypoxanthine from the common precursor molecules of hydrogen cyanide and water under this UV light. In this article, we extend our analysis to include the production of the other two important purines, guanine and xanthine. The photochemical reactions are presumed to occur within a fatty acid vesicle floating on a hot (∼80 ∘C) neutral pH ocean surface exposed to the prevailing UV-C light. Reaction-diffusion equations are resolved under different environmental conditions. Significant amounts of adenine (∼10-5 M) and guanine (∼10-6 M) are obtained within 60 Archean days, starting from realistic concentrations of the precursors hydrogen cyanide and cyanogen (∼10-5 M).

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Abstract Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a disorder of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its variants, HPRT-related hyperuricemia with neurologic dysfunction (HND) and HPRT-related hyperuricemia (HRH). The objective of this study was to characterize a cohort of Argentine patients with HPRT deficiency diagnosed in a single center. Results: Twenty nine patients were studied, including 12 LND, 15 HND and 2 HRH. The average onset age was 0.64 years for LND with motor delay as the main manifestation, 8.84 years for HND and 2.5 years for HRH; nephrological manifestations predominated as presenting features in these variants. The average diagnosis age was 3.58 years for LND, 17.21 years for HND and 2.5 years for HRH. Clinical heterogeneity was more evident in HND, even in members of the same family. All patients presented hyperuricemia and no detectable HPRT activity in erythrocyte lysate. The molecular study allowed to identify 9 different mutations in HPRT1 gene from 24 patients (11 independent pedigrees) and to establish genotype-phenotype correlation. In conclusion, this study describes the genotypic/phenotypic spectrum of HPRT deficiency in Argentine patients and highlights the need to increase awareness about the suspicion of these diseases, especially the LND variants with high clinical heterogeneity.

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Schistosoma mansoni, the parasite responsible for schistosomiasis, lacks the "de novo" purine biosynthetic pathway and depends entirely on the purine salvage pathway for the supply of purines. Numerous reports of praziquantel resistance have been described, as well as stimulated efforts to develop new drugs against schistosomiasis. Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a key enzyme of the purine salvage pathway. Here, we describe a crystallographic structure of the S. mansoni HPGRT-1 (SmHGPRT), complexed with IMP at a resolution of 2.8 Ǻ. Four substitutions were identified in the region of the active site between SmHGPRT-1 and human HGPRT. We also present data from RNA-Seq and WISH, suggesting that some isoforms of HGPRT might be involved in the process related to sexual maturation and reproduction in worms; furthermore, its enzymatic assays show that the isoform SmHGPRT-3 does not present the same catalytic efficiency as other isoforms. Finally, although other studies have previously suggested this enzyme as a potential antischistosomal chemotherapy target, the kinetics parameters reveal the impossibility to use SmHGPRT as an efficient chemotherapeutic target.

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Advanced glycation end products (AGEs) represent a set of molecules that contribute directly to the initiation and aggravation of diseases associated with ageing. AGEs are produced by the reaction between reducing sugars (or α-dicarbonyl compounds), proteins, and amino acid residues. Previous in vitro methods using non-enzymatic procedures described in the literature require an incubation period of 1⁻3 weeks to generate AGEs. In this study, the reaction time for the formation of AGEs (48 and 3 h) was significantly reduced by adaptation of methods previously described in the literature and coupling them to the free radical generation system termed hypoxanthine/xanthine oxidase assay. The incorporation of this assay into the experimental system accelerated the production of AGEs as a result of the formation of reactive oxygen species (ROS), as shown by increased fluorescence. The capacity of different classes of chemical compounds (aminoguanidine, chlorogenic acid, rutin, and methanol extracts of Hancornia speciosa Gomes) to inhibit protein glycation by acting as scavenging agents of α-dicarbonyl species was evaluated. Aminoguanidine and, especially, rutin identified in the leaf extracts of H. speciosa Gomes showed a high capacity to act as scavengers of reactive carbonyl species RCS-trapping, resulting in the inhibition of AGEs formation.

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Hypoxanthine is the major purine involved in the salvage pathway of purines in the brain. High levels of hypoxanthine are characteristic of Lesch-Nyhan Disease. Since hypoxanthine is a purine closely related to ATP formation, the aim of this study was to investigate the effect of intrastriatal hypoxanthine administration on neuroenergetic parameters (pyruvate kinase, succinate dehydrogenase, complex II, cytochrome c oxidase, and ATP levels) and mitochondrial function (mitochondrial mass and membrane potential) in striatum of rats. We also evaluated the effect of cell death parameters (necrosis and apoptosis). Wistar rats of 60 days of life underwent stereotactic surgery and were divided into two groups: control (infusion of saline 0.9%) and hypoxanthine (10 µM). Intrastriatal hypoxanthine administration did not alter pyruvate kinase activity, but increased succinate dehydrogenase and complex II activities and diminished cytochrome c oxidase activity and immunocontent. Hypoxanthine injection decreased the percentage of cells with mitochondrial membrane label and increased mitochondrial membrane potential labeling. There was a decrease in the number of live cells and an increase in the number of apoptotic cells by caused hypoxanthine. Our findings show that intrastriatal hypoxanthine administration altered neuroenergetic parameters, and caused mitochondrial dysfunction and cell death by apoptosis, suggesting that these processes may be associated, at least in part, with neurological symptoms found in patients with Lesch-Nyhan Disease.

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OBJECTIVES: This study was conducted to assess the markers of oxidative stress, myeloperoxidase (MPO), acetylcholinesterase (AChE) and xanthine oxidase (XO) activities as well as the levels of nucleotide metabolites in sickle cell anemia (SCA) patients. METHODS: Fifteen SCA treated patients and 30 health subjects (control group) were selected. The markers of oxidative stress (levels of reactive oxygen species (ROS), plasma proteins, carbonyl content, lipid peroxidation (TBARS), total thiols (T-SH), glutathione and catalase activity), MPO, AChE and XO activities as well as the levels of nucleotide metabolites were measured in SCA patients. RESULTS: ROS, thiobarbituric acid-reactive substances (TBARS) and T-SH levels as well as the activities of catalase and MPO were significantly increased while glutathione level was reduced in SCA patients. Furthermore, a significant (P < 0.001) increase in hypoxanthine level was demonstrated in SCA patients. However, the serum levels for xanthine (P < 0.01) and uric acid (P < 0.001) were decreased in SCA patients. A significant (P < 0.001) decrease in XO activity was detected in SCA patients. DISCUSSION: The altered parameters in SCA patients suggest that the generation and impairment of oxidative stress in this disease as well as antioxidant markers are contributory factors towards cellular redox homeostasis and alteration of purine metabolites.

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The aim of this study was to evaluate the levels of purine nucleosides and xanthine oxidase (XO) activity in the liver of mice chronically infected by Toxoplasma gondii and treated with diphenyl diselenide (PhSe)2. For this experiment, forty Swiss mice were used. Twenty animals were orally infected by approximately 50 bradizoites of a cystogenic ME-49 strain of T. gondii, and the same number of uninfected mice was used as a control group. Ten infected and ten uninfected mice were subcutaneously treated twice (days 1 and 20 post-infection (PI)) with 5 µmol kg-1 of (PhSe)2. On day 30 PI, liver samples were collected to measure the levels of hypoxanthine (HYPO), xanthine (XAN), uric acid (UA), and XO activity. Infected animals showed increased (P < 0.05) levels of hepatic XAN and UA, as well as XO activity compared to uninfected animals. The use of (PhSe)2 in healthy mice increased the levels of all nucleosides, but decreased XO activity compared to healthy untreated animals. The group of infected and treated animals showed increased XAN and UA levels, and XO activity compared to the healthy control group, however infected and treated mice showed a decrease in the XO activity compared to the infected untreated group. We conclude that chronic infection caused by T. gondii can induce hepatic changes, such as increased UA levels and XO activity, that can increase the pro-oxidative profile. The (PhSe)2 treatment of healthy animals altered the levels of nucleosides, possibly due to low XO activity that decreased nucleoside degradation. Finally, (PhSe)2 treatment decreased XO activity in the infected group and increased nucleoside levels; however it was unable to reduce the UA levels found during the infection.

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Hypoxanthine, the major oxypurine metabolite involved in purine's salvage pathway in the brain, is accumulated in Lesch-Nyhan disease, an inborn error of metabolism of purine. The purpose of this study was to investigate the effects of hypoxanthine intrastriatal administration on infant and young adult rats submitted to stereotactic surgery. We analyzed the effect of hypoxanthine on neuroinflammatory parameters, such as cytokine levels, immunocontent of NF-κB/p65 subunit, iNOS immunocontent, nitrite levels, as well as IBA1 and GFAP immunocontent in striatum of infant and young adult rats. We also evaluate some oxidative parameters, including reactive species production, superoxide dismutase, catalase, glutathione peroxidase activities, as well as DNA damage. Wistar rats of 21 and 60 days of life underwent stereotactic surgery and were divided into two groups: control (infusion of saline 0.9 %) and hypoxanthine (10 µM). Intrastriatal administration of hypoxanthine increased IL-6 levels in striatum of both ages of rats tested, while TNF-α increased only in 21-day-old rats. Hypoxanthine also increased nuclear immunocontent of NF-κB/p65 subunit in striatum of both ages of rats. Nitrite levels were decreased in striatum of 21-day-old rats; however, the immunocontent of iNOS was increased in striatum of hypoxanthine groups. Microglial and astrocyte activation was seen by the increase in IBA1 and GFAP immunocontent, respectively, in striatum of infant rats. All oxidative parameters were altered, suggesting a strong neurotoxic hypoxanthine role on oxidative stress. According to our results, hypoxanthine intrastriatal administration increases neuroinflammatory parameters perhaps through oxidative misbalance, suggesting that this process may be involved, at least in part, to neurological disorders found in patients with Lesch-Nyhan disease.

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Aquatic and semiaquatic mammals have the capacity of breath hold (apnea) diving. Northern elephant seals (Mirounga angustirostris) have the ability to perform deep and long duration dives; during a routine dive, adults can hold their breath for 25 min. Neotropical river otters (Lontra longicaudis annectens) can hold their breath for about 30 s. Such periods of apnea may result in reduced oxygen concentration (hypoxia) and reduced blood supply (ischemia) to tissues. Production of adenosine 5'-triphosphate (ATP) requires oxygen, and most mammalian species, like the domestic pig (Sus scrofa), are not adapted to tolerate hypoxia and ischemia, conditions that result in ATP degradation. The objective of this study was to explore the differences in purine synthesis and recycling in erythrocytes and plasma of three mammalian species adapted to different environments: aquatic (northern elephant seal) (n = 11), semiaquatic (neotropical river otter) (n = 4), and terrestrial (domestic pig) (n = 11). Enzymatic activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) was determined by spectrophotometry, and activity of inosine 5'-monophosphate dehydrogenase (IMPDH) and the concentration of hypoxanthine (HX), inosine 5'-monophosphate (IMP), adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), ATP, guanosine 5'-diphosphate (GDP), guanosine 5'-triphosphate (GTP), and xanthosine 5'-monophosphate (XMP) were determined by high-performance liquid chromatography (HPLC). The activities of HGPRT and IMPDH and the concentration of HX, IMP, AMP, ADP, ATP, GTP, and XMP in erythrocytes of domestic pigs were higher than in erythrocytes of northern elephant seals and river otters. These results suggest that under basal conditions (no diving, sleep apnea or exercise), aquatic, and semiaquatic mammals have less purine mobilization than their terrestrial counterparts.

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A stripping method for the determination of xanthine in the presence of hypoxanthine at the submicromolar concentration levels is described. The method is based on controlled adsorptive accumulation at the thin-film mercury electrode followed by a fast linear scan voltammetric measurement of the surface species. Optimum experimental conditions were found to be the use of 1.0 × 10(-3) mol L(-1) NaOH solution as supporting electrolyte, an accumulation potential of 0.00 V for xanthine and -0.50 V for hypoxanthine-copper, and a linear scan rate of 200 mV second(-1). The response of xanthine is linear over the concentration ranges of 20-140 ppb. For an accumulation time of 30 minutes, the detection limit was found to be 36 ppt (2.3 × 10(-10) mol L(-1)). Adequate conditions for measuring the xanthine in the presence of hypoxanthine, copper and other metals, uric acid, and other nitrogenated bases were also investigated. The utility of the method is demonstrated by the presence of xanthine associated with hypoxanthine, uric acid, nitrogenated bases, ATP, and ssDNA.

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In the present study, we investigated the in vitro effect of hypoxanthine on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase, as well as on thiobarbituric-acid-reactive substances (TBA-RS), in the renal cortex and medulla of rats. Results showed that hypoxanthine, at a concentration of 10.0 µM, enhanced the activities of CAT and SOD in the renal cortex of 15-, 30- and 60-day-old rats, enhanced SOD activity in the renal medulla of 60-day-old rats and enhanced TBA-RS levels in the renal medulla of 30-day-old rats, as compared with controls. Furthermore, we also verified the influence of allopurinol (an inhibitor of xanthine oxidase), as well as of the antioxidants, trolox and ascorbic acid on the effects elicited by hypoxanthine on the parameters tested. Allopurinol and/or administration of antioxidants prevented most alterations caused by hypoxanthine in the oxidative stress parameters evaluated. Data suggest that hypoxanthine alters antioxidant defences and induces lipid peroxidation in the kidney of rats; however, in the presence of allopurinol and antioxidants, some of these alterations in oxidative stress were prevented. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by hypoxanthine.

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O objetivo deste trabalho foi avaliar a síntese de proteína microbiana, ureia e glicose sanguíneas, em caprinos Boer alimentados com níveis de torta de licuri nas dietas. Utilizaram-se 20 caprinos machos não castrados ¾ Boer com peso vivo médio 18 kg distribuídos nos quatro tratamentos. Os animais foram mantidos em baias suspensas com um m2 e água a vontade. As dietas foram formuladas conforme o NRC (2007) e os ingredientes utilizados foram: 50% feno de Tifton-85 (Cynodon sp), milho moído, farelo de soja, suplemento vitamínico-mineral e torta de licuri. Os tratamentos foram: 1) 0% de adição (MS%) de torta de licuri na dieta, 2) 15% de adição de torta de licuri, 3) 30% de adição de torta de licuri e 4) 45% de adição de torta de licuri. O experimento teve a duração de 17 dias, sendo 10 dias de adaptação dos animais as dietas. A inclusão da torta de licuri na dieta de caprinos promoveu redução nos níveis de ureia e glicose nos caprinos. O volume urinário dos caprinos reduziu de forma linear com a inclusão de torta de licuri na dieta. A inclusão de torta de licuri nas dietas de caprinos promoveu redução linear na excreção de alantoína xantina e hipoxantina e derivados de purinas totais (PD) nas amostras das coletas totais de urina em resposta a inclusão da torta de licuri na dieta. Com base na produção de proteína microbiana e os parâmetros sanguíneos dos caprinos alimentados com torta de licuri, pode-se utilizar até 15% de inclusão na dieta.(AU)

The objective of this study was to determine the ideal level of licury cake in the diet of Boer goats through microbial synthesis estimated based on the presence of purine derivatives in the urine and on blood urea and glucose parameters. Twenty uncastrated one-year-old ¾ Boer goats with an average body weight of 18 kg were distributed in a completely randomized design. Each animal was confined to a one m2 suspended stall with access to water ad libitum. The diets were formulated in accordance with the NRC (2007), and the ingredients were: 50% Tifton-85 (Cynodon sp) hay, corn meal, soybean meal, premixed vitamin and mineral supplement, and licury cake. The treatments were: 1) 0% of the goats total diet composed of licury cake (DM basis), 2) 15% of the total diet composed of licury cake, 3) 30% of the diet composed of licury cake, and 4) 45% of the diet composed of licury cake. The experiment lasted for 17 days. The first 10 days were used to adapt the animals to the diets and facilities. The inclusion of the licury cake in the goats diets reduced the levels of blood nitrogen and glucose. Urinary excretion decreased linearly with the inclusion of licury cake in the diet. The inclusion of licury cake in the goats diets also caused a linear reduction in the excretion of allantoin, xanthine and hypoxanthine and total purine derivative (PD) in urine samples. Based on the microbial protein production and blood parameters of goats fed with licury cake, up to 15% of the goat diet may be composed of licury cake.(AU)

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O objetivo deste trabalho foi avaliar a síntese de proteína microbiana, ureia e glicose sanguíneas, em caprinos Boer alimentados com níveis de torta de licuri nas dietas. Utilizaram-se 20 caprinos machos não castrados ¾ Boer com peso vivo médio 18 kg distribuídos nos quatro tratamentos. Os animais foram mantidos em baias suspensas com um m2 e água a vontade. As dietas foram formuladas conforme o NRC (2007) e os ingredientes utilizados foram: 50% feno de Tifton-85 (Cynodon sp), milho moído, farelo de soja, suplemento vitamínico-mineral e torta de licuri. Os tratamentos foram: 1) 0% de adição (MS%) de torta de licuri na dieta, 2) 15% de adição de torta de licuri, 3) 30% de adição de torta de licuri e 4) 45% de adição de torta de licuri. O experimento teve a duração de 17 dias, sendo 10 dias de adaptação dos animais as dietas. A inclusão da torta de licuri na dieta de caprinos promoveu redução nos níveis de ureia e glicose nos caprinos. O volume urinário dos caprinos reduziu de forma linear com a inclusão de torta de licuri na dieta. A inclusão de torta de licuri nas dietas de caprinos promoveu redução linear na excreção de alantoína xantina e hipoxantina e derivados de purinas totais (PD) nas amostras das coletas totais de urina em resposta a inclusão da torta de licuri na dieta. Com base na produção de proteína microbiana e os parâmetros sanguíneos dos caprinos alimentados com torta de licuri, pode-se utilizar até 15% de inclusão na dieta.

The objective of this study was to determine the ideal level of licury cake in the diet of Boer goats through microbial synthesis estimated based on the presence of purine derivatives in the urine and on blood urea and glucose parameters. Twenty uncastrated one-year-old ¾ Boer goats with an average body weight of 18 kg were distributed in a completely randomized design. Each animal was confined to a one m2 suspended stall with access to water ad libitum. The diets were formulated in accordance with the NRC (2007), and the ingredients were: 50% Tifton-85 (Cynodon sp) hay, corn meal, soybean meal, premixed vitamin and mineral supplement, and licury cake. The treatments were: 1) 0% of the goat’s total diet composed of licury cake (DM basis), 2) 15% of the total diet composed of licury cake, 3) 30% of the diet composed of licury cake, and 4) 45% of the diet composed of licury cake. The experiment lasted for 17 days. The first 10 days were used to adapt the animals to the diets and facilities. The inclusion of the licury cake in the goat’s diets reduced the levels of blood nitrogen and glucose. Urinary excretion decreased linearly with the inclusion of licury cake in the diet. The inclusion of licury cake in the goat’s diets also caused a linear reduction in the excretion of allantoin, xanthine and hypoxanthine and total purine derivative (PD) in urine samples. Based on the microbial protein production and blood parameters of goats fed with licury cake, up to 15% of the goat diet may be composed of licury cake.

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Insulin acts in the hypothalamus, decreasing food intake (FI) by the IR/PI3K/Akt pathway. This pathway is impaired in obese animals and endoplasmic reticulum (ER) stress and low-grade inflammation are possible mechanisms involved in this impairment. Here, we highlighted the amygdala as an important brain region for FI regulation in response to insulin. This regulation was dependent on PI3K/AKT pathway similar to the hypothalamus. Insulin was able to decrease neuropeptide Y (NPY) and increase oxytocin mRNA levels in the amygdala via PI3K, which may contribute to hypophagia. Additionally, obese rats did not reduce FI in response to insulin and AKT phosphorylation was decreased in the amygdala, suggesting insulin resistance. Insulin resistance was associated with ER stress and low-grade inflammation in this brain region. The inhibition of ER stress with PBA reverses insulin action/signaling, decreases NPY and increases oxytocin mRNA levels in the amygdala from obese rats, suggesting that ER stress is probably one of the mechanisms that induce insulin resistance in the amygdala.

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A validade comercial de sardinhas das espécies Sardinella brasiliensis e Cetengraulis edentulus mantidas sob refrigeração em gelo (0+2°C) foi determinada por parâmetros analíticos físico-químicos, bacteriológicos e sensorial. Nas duas amostras, os teores de Bases Voláteis Totais (BVT) e Trimetilamina (TMA) atingiram o limite máximo recomendado na legislação (30mg N100g-1 para BVT e 4mg N100g-1 para TMA) após 14 e 8 dias de estocagem, respectivamente. O conteúdo de histamina, putrescina e cadaverina se manteve em níveis inferiores a 2.0µg g-1 nas duas amostras durante o período de estocagem. A produção de hipoxantina variou de 0,65 a 2,62µmol g-1 nas amostras de S. brasiliensis e de 1,40 a 2,09µmol g-1 nas amostras de C. edentulus. A contagem inicial de Enterobacteriaceae foi de 3,81log UFC g-1 e 3,82log UFC g-1 atingindo, ao final de 18 dias de estocagem, 6,57log UFC g-1 e 6,87log UFC g-1, nas amostras de S. brasiliensis e C. edentulus, respectivamente. Para as contagens de bactérias heterotróficas aeróbias mesófilas e psicrotróficas, o limite de 7log UFC g-1 preconizado na legislação internacional foi alcançado após o 12° e 8° dias de estocagem nas amostras de S. brasiliensis e após o 12° e 6° dias de estocagem nas amostras de C. edentulus, respectivamente. O método de índice de qualidade sugeriu, para as amostras de S. brasiliensis, um limite de consumo aceitável inferior a 11 e, para as amostras de C. edentulus, um limite de aceitabilidade inferior a 14. Foi proposta a validade comercial de dez dias para a S. brasiliensis e nove dias para o C. edentulus.

Theshelf life of sardines of Sardinella brasiliensis and Cetengraulis edentulus species kept on ice at +2°Cwas determined by physical-chemical, bacteriological and sensory parameters. In both samples, the levels of Total Volatile Bases (TVB) and Trimethylamine (TMA) reached the limits recommended by law (30mg N 100g-1 for TVB and 4mgN100g-1 for TMA) after 14 and 8 days of storage, respectively. The contents of histamine, putrescine and cadaverine remained at levels below 2.0µg g-1 in both samples during the storage period. The hypoxanthine production ranged from 0.65 to 2.62µmol g-1 in samples of S. brasiliensis and 1.40 to 2.09µmol g-1 in samples of C. edentulus. The initial count of Enterobacteriaceae was 3.81logCFU g-1 and 3.82logCFU g-1 reaching, after 18days of storage, 6.57logCFU g-1 and 6.87logCFU g-1, in samples of S. brasiliensis and C. edentulus, respectively. For heterotrophic bacteria aerobic mesophilic and psychrotrophic count the limit of 7logCFU g-1 recommended by international legislation was reached after12 and 8days of storage in samples of S. brasiliensis and after 12 and 6days of storage in samples of C. edentulus, respectively. The quality index method suggested for samples of S. brasiliensis, a limit of acceptable consumption less than 11 and for samples of C. edentulus a limit of acceptability below 14. As a result of this study, we recommend a shelf life of ten days for the S. brasiliensis and nine days for the C. edentulus.

RESUMEN

Theshelf life of sardines of Sardinella brasiliensis and Cetengraulis edentulus species kept on ice at +2°Cwas determined by physical-chemical, bacteriological and sensory parameters. In both samples, the levels of Total Volatile Bases (TVB) and Trimethylamine (TMA) reached the limits recommended by law (30mg N 100g-1 for TVB and 4mgN100g-1 for TMA) after 14 and 8 days of storage, respectively. The contents of histamine, putrescine and cadaverine remained at levels below 2.0µg g-1 in both samples during the storage period. The hypoxanthine production ranged from 0.65 to 2.62µmol g-1 in samples of S. brasiliensis and 1.40 to 2.09µmol g-1 in samples of C. edentulus. The initial count of Enterobacteriaceae was 3.81logCFU g-1 and 3.82logCFU g-1 reaching, after 18days of storage, 6.57logCFU g-1 and 6.87logCFU g-1, in samples of S. brasiliensis and C. edentulus, respectively. For heterotrophic bacteria aerobic mesophilic and psychrotrophic count the limit of 7logCFU g-1 recommended by international legislation was reached after12 and 8days of storage in samples of S. brasiliensis and after 12 and 6days of storage in samples of C. edentulus, respectively. The quality index method suggested for samples of S. brasiliensis, a limit of acceptable consumption less than 11 and for samples of C. edentulus a limit of acceptability below 14. As a result of this study, we recommend a shelf life of ten days for the S. brasiliensis and nine days for the C. edentulus.

A validade comercial de sardinhas das espécies Sardinella brasiliensis e Cetengraulis edentulus mantidas sob refrigeração em gelo (0+2°C) foi determinada por parâmetros analíticos físico-químicos, bacteriológicos e sensorial. Nas duas amostras, os teores de Bases Voláteis Totais (BVT) e Trimetilamina (TMA) atingiram o limite máximo recomendado na legislação (30mg N100g-1 para BVT e 4mg N100g-1 para TMA) após 14 e 8 dias de estocagem, respectivamente. O conteúdo de histamina, putrescina e cadaverina se manteve em níveis inferiores a 2.0µg g-1 nas duas amostras durante o período de estocagem. A produção de hipoxantina variou de 0,65 a 2,62µmol g-1 nas amostras de S. brasiliensis e de 1,40 a 2,09µmol g-1 nas amostras de C. edentulus. A contagem inicial de Enterobacteriaceae foi de 3,81log UFC g-1 e 3,82log UFC g-1 atingindo, ao final de 18 dias de estocagem, 6,57log UFC g-1 e 6,87log UFC g-1, nas amostras de S. brasiliensis e C. edentulus, respectivamente. Para as contagens de bactérias heterotróficas aeróbias mesófilas e psicrotróficas, o limite de 7log UFC g-1 preconizado na legislação internacional foi alcançado após o 12° e 8° dias de estocagem nas amostras de S. brasiliensis e após o 12° e 6° dias de estocagem nas amostras de C. edentulus, respectivamente. O método de índice de qualidade sugeriu, para as amostras de S. brasiliensis, um limite de consumo aceitável inferior a 11 e, para as amostras de C. edentulus, um limite de aceitabilidade inferior a 14. Foi proposta a validade comercial de dez dias para a S. brasiliensis e nove dias para o C. edentulus.

RESUMEN

Theshelf life of sardines of Sardinella brasiliensis and Cetengraulis edentulus species kept on ice at +2°Cwas determined by physical-chemical, bacteriological and sensory parameters. In both samples, the levels of Total Volatile Bases (TVB) and Trimethylamine (TMA) reached the limits recommended by law (30mg N 100g-1 for TVB and 4mgN100g-1 for TMA) after 14 and 8 days of storage, respectively. The contents of histamine, putrescine and cadaverine remained at levels below 2.0µg g-1 in both samples during the storage period. The hypoxanthine production ranged from 0.65 to 2.62µmol g-1 in samples of S. brasiliensis and 1.40 to 2.09µmol g-1 in samples of C. edentulus. The initial count of Enterobacteriaceae was 3.81logCFU g-1 and 3.82logCFU g-1 reaching, after 18days of storage, 6.57logCFU g-1 and 6.87logCFU g-1, in samples of S. brasiliensis and C. edentulus, respectively. For heterotrophic bacteria aerobic mesophilic and psychrotrophic count the limit of 7logCFU g-1 recommended by international legislation was reached after12 and 8days of storage in samples of S. brasiliensis and after 12 and 6days of storage in samples of C. edentulus, respectively. The quality index method suggested for samples of S. brasiliensis, a limit of acceptable consumption less than 11 and for samples of C. edentulus a limit of acceptability below 14. As a result of this study, we recommend a shelf life of ten days for the S. brasiliensis and nine days for the C. edentulus.

A validade comercial de sardinhas das espécies Sardinella brasiliensis e Cetengraulis edentulus mantidas sob refrigeração em gelo (0+2°C) foi determinada por parâmetros analíticos físico-químicos, bacteriológicos e sensorial. Nas duas amostras, os teores de Bases Voláteis Totais (BVT) e Trimetilamina (TMA) atingiram o limite máximo recomendado na legislação (30mg N100g-1 para BVT e 4mg N100g-1 para TMA) após 14 e 8 dias de estocagem, respectivamente. O conteúdo de histamina, putrescina e cadaverina se manteve em níveis inferiores a 2.0µg g-1 nas duas amostras durante o período de estocagem. A produção de hipoxantina variou de 0,65 a 2,62µmol g-1 nas amostras de S. brasiliensis e de 1,40 a 2,09µmol g-1 nas amostras de C. edentulus. A contagem inicial de Enterobacteriaceae foi de 3,81log UFC g-1 e 3,82log UFC g-1 atingindo, ao final de 18 dias de estocagem, 6,57log UFC g-1 e 6,87log UFC g-1, nas amostras de S. brasiliensis e C. edentulus, respectivamente. Para as contagens de bactérias heterotróficas aeróbias mesófilas e psicrotróficas, o limite de 7log UFC g-1 preconizado na legislação internacional foi alcançado após o 12° e 8° dias de estocagem nas amostras de S. brasiliensis e após o 12° e 6° dias de estocagem nas amostras de C. edentulus, respectivamente. O método de índice de qualidade sugeriu, para as amostras de S. brasiliensis, um limite de consumo aceitável inferior a 11 e, para as amostras de C. edentulus, um limite de aceitabilidade inferior a 14. Foi proposta a validade comercial de dez dias para a S. brasiliensis e nove dias para o C. edentulus.