Physiochemical and nutritional evaluation of whole kumquat fruits powder and its protective effect on thyroid hormones and blood sugar levels in diabetic rats / Avaliação físico-química e nutricional de frutas inteiras de kumquat em pó e seu efeito protetor sobre os hormônios da tireoide e os níveis de açúcar no sangue em ratos diabéticos

The present study was conducted to evaluate the chemical composition, antioxidant activity and hypoglycemic effects of whole kumquat (Ku) powder in diabetic rats fed a high-fat-high-cholesterol (HFHC) diet. The antioxidant activities were evaluated using stable 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical scavenging method, 2,2'-azinobis (3-ethyl benzo thiazoline-6-sulphonic acid) radical cation (ABTS) and Ferric reducing antioxidant power (FRAP). Total phenolic content was (51.85 mg GAE/g) and total flavonoid content was (0.24 mg Cateachin Equivalent, CE/g). DPPH and ABTS values were 3.32 and 3.98 mg Trolox equivalent (TE)/g where FRAP value was 3.00 mM Fe²+/kg dry material. A total of 90 albino rats were used in the present study. Rats group were as follows: normal diet; normal treated (2, 4, and 6% Ku.), diabetic rats (non-treated), diabetic + HFHC diet (non-treated), HFHC (non-treated), Diabetic (treated), HFHC (treated) and Diabetic + HFHC (treated). The diets were followed for 8 weeks. Blood samples were collected at the end of the experiment. Serum glucose was recorded and thyroid hormones (T4, Thyroxine and T3, Triiodothyronine) were conducted. Diet supplemented with Kumquat at different concentrations have a hypoglycemic effect and improve the thyroid hormones of both diabetic rats and HFHC diabetic rats.

O presente estudo foi conduzido para avaliar a composição química, a atividade antioxidante e os efeitos hipoglicêmicos do pó de kumquat (Ku) em ratos diabéticos alimentados com uma dieta rica em gordura e colesterol (HFHC). As atividades antioxidantes foram avaliadas usando o método de eliminação de radicais livres de 1,1-difenil 2-picrilhidrazil (DPPH), 2,2'-azinobis (ácido 3-etilbenzotiazolina-6-sulfônico) radical cátion (ABTS) e antioxidante redutor férrico potência (FRAP). O conteúdo fenólico total foi (51,85 mg GAE / g) e o conteúdo total de flavonoides foi (0,24 mg Cateachin Equivalent, CE / g). Os valores de DPPH e ABTS foram 3,32 e 3,98 mg equivalente de Trolox (TE) / g, em que o valor de FRAP foi de 3,00 mM Fe²+ / kg de material seco. Um total de 90 ratos albinos foi usado no presente estudo. O grupo dos ratos foi o seguinte: dieta normal: tratados normais (2, 4 e 6% Ku.), ratos diabéticos (não tratados), diabéticos + dieta HFHC (não tratados), HFHC (não tratados), diabéticos (tratados), HFHC (tratados) e diabéticos + HFHC (tratados). As dietas foram seguidas por 8 semanas. Amostras de sangue foram coletadas ao final do experimento. A glicose sérica foi registrada e os hormônios tireoidianos (T4, Tiroxina e T3, Triiodotironina) foram conduzidos. A dieta suplementada com kumquat em diferentes concentrações tem um efeito hipoglicêmico e melhora os hormônios tireoidianos tanto de ratos diabéticos quanto de ratos diabéticos com HFHC.

Doramectin inhibits glioblastoma cell survival via regulation of autophagy in vitro and in vivo.

Glioblastoma (GBM) is one of the most widespread and lethal types of cancer. However, there are currently no drugs or therapeutic strategies that can completely cure GBM. Doramectin (DRM) has a broad range of activities against endoparasites and ectoparasites, and is extensively used in livestock. In the present study, the effect of DRM on the induction of autophagy in U87 and C6 GBM and glioma cell lines, as well as the mechanism of autophagy, were examined. First, transmission electron microscopy, plasmid transfection and western blot analysis demonstrated that DRM could induce autophagy in U87 and C6 cells in vitro. Next, MTT and colony formation assays revealed that DRM­induced autophagy prevented U87 and C6 cell viability and colony formation ratio. In addition, DRM­induced autophagy promoted U87 and C6 cell apoptosis, as indicated by DAPI analysis and flow cytometry. Furthermore, transcriptome analysis demonstrated that DRM modulated a number of genes and pathways involved in autophagy. In a nude mouse xenograft model, immunohistochemical staining and the TUNEL assay demonstrated that the effect of DRM on the tumor was consistent with that in vivo. These data indicated that DRM induced autophagy mainly by blocking the PI3K/AKT/mTOR signaling pathway in GBM cells. DRM­induced autophagy promoted the inhibition of GBM cell proliferation and apoptosis in vitro and in vivo. The present study suggested that DRM may be an effective drug for the treatment of GBM.

Nanochitosan Effect on Biomolecular, Hypolipidemic in Rats and Incorporation in Functional Yogurt.

<b>Background and Objective:</b> Chitosan has many functional properties and biological activities. This work aimed to prepare and characterize Chitosan Nanoparticles (CN). Then, evaluate the hypolipidemic and antioxidant effect of CN in rats. Incorporate CN in camel yogurt and evaluation of yogurt properties. <b>Materials and Methods:</b> Chitosan Nanoparticles (CN) were prepared and analyzed for the size, zeta potential and poly Polydispersity Index (PDI). Total 24 rats were divided into 4 groups, the negative control group was fed on the basal diet and the positive control group was fed on a High-Fat Diet (HFD), the group I and II were fed on the HFD+(CC) or (CN). The feeding period was 6 weeks. Prepared and Characterization stirred camel yogurt fortified by CN. <b>Results:</b> CN the size was 27.20 nm, ζ-potential+38.78. After the feeding period for CN and CC groups were a decrease in body weight, serum lipid profile and liver function in both tested groups and an increase in HDL-cholesterol and an increase in antioxidants in the CN group more than that in the CC group was observed. mRNA expression with qPCR for hepatic PPARγ, HL, GSS and CYP2E1 genes was performed to investigate the alterations in their levels after CN treatment on the liver of rats fed with HFD. <b>Conclusion:</b> CN possesses the ability to improve the impairment of lipid metabolism as strongly associated with gene expressions related to lipogenesis and oxidative stress. Also, the addition of 2% CN to camel yogurt gave sensory acceptable and microbiological quality.

The atlas of RNase H antisense oligonucleotide distribution and activity in the CNS of rodents and non-human primates following central administration.

Antisense oligonucleotides (ASOs) have emerged as a new class of drugs to treat a wide range of diseases, including neurological indications. Spinraza, an ASO that modulates splicing of SMN2 RNA, has shown profound disease modifying effects in Spinal Muscular Atrophy (SMA) patients, energizing efforts to develop ASOs for other neurological diseases. While SMA specifically affects spinal motor neurons, other neurological diseases affect different central nervous system (CNS) regions, neuronal and non-neuronal cells. Therefore, it is important to characterize ASO distribution and activity in all major CNS structures and cell types to have a better understanding of which neurological diseases are amenable to ASO therapy. Here we present for the first time the atlas of ASO distribution and activity in the CNS of mice, rats, and non-human primates (NHP), species commonly used in preclinical therapeutic development. Following central administration of an ASO to rodents, we observe widespread distribution and target RNA reduction throughout the CNS in neurons, oligodendrocytes, astrocytes and microglia. This is also the case in NHP, despite a larger CNS volume and more complex neuroarchitecture. Our results demonstrate that ASO drugs are well suited for treating a wide range of neurological diseases for which no effective treatments are available.

PINK1/PRKN-dependent mitophagy in the burn injury model.

Burn injury leads to mitochondrial dysfunction and autophagy, also known as mitophagy. The alleviation of mitochondrial damage may be a potential method for the treatment of burn injury and complications. In this animal study, we analyzed the expression of mitochondrial damage- and mitophagy-related factors, specifically PINK1 and PRKN. The results showed mitochondria damage in the skin; compared with the normal control group, genes involved in the mitochondrial damage, such as Nrf-1, UQCRC2, CYC1, and NDUFA9, as well as in the mitophagy, including PINK1, PRKN, MFN1, and USP30, were differentially expressed. Furthermore, PINK1 interacted with PRKN and participated in mitophagy in the skin. In conclusion, our data reveal more about the mechanism underlying mitophagy in burns, providing a potential clinical treatment.

Disruption of insulin receptor substrate-2 impairs growth but not insulin function in rats.

Insulin receptor substrate (IRS)-2, along with IRS-1, is a key signaling molecule that mediates the action of insulin and insulin-like growth factor (IGF)-I. The activated insulin and IGF-I receptors phosphorylate IRSs on tyrosine residues, leading to the activation of downstream signaling pathways and the induction of various physiological functions of insulin and IGF-I. Studies using IRS-2 knockout (KO) mice showed that the deletion of IRS-2 causes type 2 diabetes due to peripheral insulin resistance and impaired ß-cell function. However, little is known about the roles of IRS-2 in other animal models. Here, we created IRS-2 KO rats to elucidate the physiological functions of IRS-2 in rats. The body weights of IRS-2 KO rats at birth were lower compared with those of their WT littermates. The postnatal growth of both male and female IRS-2 KO rats was also suppressed. Compared with male WT rats, the glucose and insulin tolerance of male IRS-2 KO rats were slightly enhanced, whereas a similar difference was not observed between female WT and IRS-2 KO rats. Besides the modestly increased insulin sensitivity, male IRS-2 KO rats displayed the enhanced insulin-induced activation of the mTOR complex 1 pathway in the liver compared with WT rats. Taken together, these results indicate that in rats, IRS-2 plays important roles in the regulation of growth but is not essential for the glucose-lowering effects of insulin.

Modulation of gut microbiota in rats fed whole egg diets by processing duck egg to preserved egg.

Pidan, as the preserved duck egg, is a traditional alkaline-pickled food in China. Previous studies have suggested preserved egg white has an anti-inflammatory effect, though the mechanism of action was unclear. In this work, the difference of peptides distribution in the digestive products was identified from those of duck egg. The effects of preserved egg diet on the modulation of gut microbiota as well as the alteration in fecal metabolites were further investigated. Minor variations of gut microbiota in phylum level were observed between preserved and fresh duck egg diet groups, even though, preserved egg diet intake attributed to increases in the relative abundance of Prevotella and Phascolarctobacterium (p < 0.05), while Ruminococcaceae and Allobaculum were quantitatively decreased (p < 0.05). In terms of metabolites, the contents of acetic acid (p < 0.01) and propionic acid (p < 0.05) were significantly increased in the preserved egg diet group. It was speculated that the preserved egg diet might alter the proportion of short-chain fatty acids (SCFAs) in the gut of rats by modulating specific intestinal bacteria, and subsequently play an active role in anti-inflammatory effects. Compared to the fresh egg group, the bacterial produced SCFAs of preserved egg group were increased in abundance (p < 0.05), which may have potential anti-obesity and anti-inflammatory effects. The results provide a novel insight into the relationship between preserved egg intake, gut microbiota and potential positive effects on host health.

In vitro metabolism of imidacloprid and acetamiprid in rainbow trout and rat.

Providing an alternative to pyrethroids, organophosphates, and carbamates, the neonicotinoids are now the most widely used insecticides in the world. They are water soluble and relatively stable in soil and water which allows for run-off through surface waters and thus potentially impacting aquatic species and environments.While the mammalian metabolism of neonicotinoids has been studied extensively, there is a lack of understanding of their metabolism in fish species. The current study constitutes the first report of the metabolism of imidacloprid (IMI) and acetamiprid (AC) in rainbow trout.Formation of respective metabolites 5-hydroxy-imidacloprid and N-desmethyl-acetamiprid was conserved across orders of biological organization in both microsomal and liver slice assays.Michaelis-Menten kinetics were determined for the microsomal conversion of IMI to 5-hydroxy-imidacloprid in rainbow trout (Km = 79.2 µM; Vmax = 0.75 pmole/min/mg) and rat (Km = 158.7 µM; Vmax = 38.4 pmole/min/mg). Kinetics for the microsomal demethylation of AC to N-desmethyl-acetamiprid were determined in the rat (Km = 70.9 µM; Vmax = 10 pmoles/min/mg). N-desmethyl-acetamiprid was found in detectable but below quantifiable levels across the range of test concentrations which precluded a calculation of kinetic rate constants in rainbow trout (RBT).Ultimately, the formation of the metabolites 5-hydroxy-imidacloprid and N-desmethyl-acetamiprid was conserved across RBT and rat species.

Effects of extruded whole-grain sorghum (Sorghum bicolor (L.) Moench) based diets on calcium absorption and bone health of growing Wistar rats.

Apparent calcium absorption, total bone mineral content and density, and mineral contents of the right femur were studied using a growing rat model. Twenty-four male Wistar rats were fed with diets based on extruded whole grain red (RSD) or white sorghum (WSD), and control diet (CD) up to 60 days. The animals fed with sorghum diets consumed less and gained less weight compared to those fed with CD, but the efficiency of all diets was similar. Calcium intake was lower in animals fed with sorghum diets, related to the lower total intake of these animals. Apparent calcium absorption in animals fed with RSD was lower than in those fed with CD (CD: 72.7%, RSD: 51.0%, WSD: 64.8%). No significant differences in bone mineral density of total body, spin, femur, distal femur, tibia and proximal tibia were observed among the groups. However, Ca and P contents in the right femur of the rats consuming RSD were lower, indicating a certain imbalance in the metabolism of these minerals.

Evaluation of copper metabolism in neonatal rats by speciation analysis using liquid chromatography hyphenated to ICP mass spectrometry.

It is known that copper (Cu) is highly accumulated in several organs in the perinatal period, suggesting changes in Cu metabolism with development, although the precise mechanisms are still unclear. To elucidate the mechanisms underlying Cu accumulation in the organs of neonatal rats, we performed speciation analysis using high-performance liquid chromatography hyphenated to inductively coupled plasma mass spectrometry. In the neonatal rat liver immediately after birth, the Cu concentration was elevated 10-fold compared to that in the juvenile rat liver. Most of the accumulated Cu was bound to metallothionein, although Cu in Cu, zinc-superoxide dismutase (SOD) was reduced. Contrary to the hepatic Cu accumulation, the serum Cu concentrations in the neonatal rats were low due to the decreased amount of Cu bound to ceruloplasmin. The mRNA expression of antioxidant protein 1 (Atox1), a Cu chaperone that transports Cu to Atp7b, remained low up to two weeks after birth. These results suggest that Cu accumulation in the neonatal rat liver is caused by the low expression of Atox1, and the accumulation is useful to distribute Cu to Cu-containing anti-oxidative enzymes (e.g., SOD and Atox1) after respiration starts.

A preliminary study of fonio-moringa seed meal-based complementary food in Wistar rats.

Effect of fonio-moringa seed meal (FMSM)-based complementary food in Wistar rats was assessed in a 28 days balanced study. Seventy, 21-day-old Wistar rats were allotted to seven groups in a completely randomized design. Infant weaning foods (IWFs) 1, 2, 3, 4, and 5 had 0%, 5%, 10%, 15%, and 20% FMSM inclusion levels, respectively, while two commercial IWFs purchased were coded CFT and CFC. The water absorption capacity, swelling power, and the pasting properties, except peak time varied (p < .05) among the IWFs. Rats fed on IWFs 3 and 4 had comparable weight gain with those fed on the commercial foods. The heart and kidney relative weights were influenced (p < .05), while villus length (duodenum) of the rats were significant (p < .05). The blood indices were not significant, but the alanine aminotransferase and cholesterol levels ranged 15.65-32.25 µ/dl and 75.75-94.55 mg/100 ml, respectively. Incorporation of 10% FMSM is recommended in IWFs. PRACTICAL APPLICATIONS: The need to reduce hunger and starvation among the less-privileged people in society is becoming increasingly important. Specifically, many infants, preschool and school children are often not having access to nutritive foods that will enhance their mental alertness. The commercial IWFs on sale in Nigeria are in most cases high in prices and consequently out of the reach of the populace. Fonio is a starchy grain with an important potential not only as a survival food but as a compliment for standard diets. Also, moringa seed is known to be of nutritional value. Most infant formulae are based on maize and soybean and it is hoped that the incorporation of FMSM in the infant weaning formula will help to increase the nutritive value and stem the cost of IWFs.

Molecular complexity of the major urinary protein system of the Norway rat, Rattus norvegicus.

Major urinary proteins (MUP) are the major component of the urinary protein fraction in house mice (Mus spp.) and rats (Rattus spp.). The structure, polymorphism and functions of these lipocalins have been well described in the western European house mouse (Mus musculus domesticus), clarifying their role in semiochemical communication. The complexity of these roles in the mouse raises the question of similar functions in other rodents, including the Norway rat, Rattus norvegicus. Norway rats express MUPs in urine but information about specific MUP isoform sequences and functions is limited. In this study, we present a detailed molecular characterization of the MUP proteoforms expressed in the urine of two laboratory strains, Wistar Han and Brown Norway, and wild caught animals, using a combination of manual gene annotation, intact protein mass spectrometry and bottom-up mass spectrometry-based proteomic approaches. Cluster analysis shows the existence of only 10 predicted mup genes. Further, detailed sequencing of the urinary MUP isoforms reveals a less complex pattern of primary sequence polymorphism in the rat than the mouse. However, unlike the mouse, rat MUPs exhibit added complexity in the form of post-translational modifications, including the phosphorylation of Ser4 in some isoforms, and exoproteolytic trimming of specific isoforms. Our results raise the possibility that urinary MUPs may have different roles in rat chemical communication than those they play in the house mouse. Shotgun proteomics data are available via ProteomExchange with identifier PXD013986.

Nutritional performance and antioxidant activities of roasted and unroasted sprouted sorghum-based weaning diets in Wistar rats.

The nutritional performance and antioxidant profile of sprouted sorghum-based weaning diets were evaluated in weaning wistar rats. Rats were fed basal diet, unroasted germinated sorghum-based diet, roasted germinated sorghum-based diet, or a commercial weaning feed (nutrend) for 28 days. Energy, carbohydrate, crude protein, lipids, crude fiber, and ash contents of the sorghum-based diets compared significantly with FAO/WHO recommendations. Contrastingly, moisture content of the germinated sorghum-based diet was higher than the recommendation. Weight gain, feed efficiency ratio, protein efficiency ratio, net protein utilization, biological value, and digestibility of unroasted germinated sorghum-based diet-fed rats compared significantly with Nutrend. Roasted germinated sorghum-based diet produced differential effects on these indices. The unroasted germinated sorghum-based diet significantly raised the antioxidant enzymes in the rat liver and kidney. Overall, evidence from the study indicates that unroasted germinated sorghum-based diet improves the nutritional performance and the antioxidants of weaning rats compared to the roasted germinated sorghum-based diet. PRACTICAL APPLICATIONS: The provision of nutritionally adequate food from local sources during the weaning period of infants continues to be a major source of concern in developing countries. The formulated unroasted sprouted sorghum-based diet can be adapted and used as weaning food. Furthermore, the diet can be processed and developed into a weaning food.

Expression of genome defence protein members in proliferating and quiescent rat male germ cells and the Nuage dynamics.

During epigenetic reprogramming germ cells activate alternative mechanisms to maintain the repression retrotransposons. This mechanism involves the recruitment of genome defence proteins such as MAEL, PIWIL4 and TDRD9, which associate with piRNAs and promote Line-1 silencing. MAEL, PIWIL4 and TDRD9 form the piP-bodies, which organization and dynamics vary according to the stage of germ cell epigenetic reprogramming. Although these data have been well documented in mice, it is not known how this mechanism operates in the rat. Thus, the aim of this study was to describe the distribution and interaction of MAEL, PIWIL4, TDRD9 and DAZL during rat germ cell development and check whether specific localization of these proteins is related to the distribution of Line-1 aggregates. Rat embryo gonads at 15 days post-conception (dpc), 16dpc and 19dpc were submitted to MAEL, PIWIL4, TDRD9 and DAZL immunolabelling. The gonads of 19dpc embryos were submitted to the double-labelling of MAEL/DAZL, TDRD9/MAEL and PIWIL4/MAEL. The 19dpc gonads were submitted to co-immunoprecipitation assays and fluorescent in situ hybridization for Line-1 detection. MAEL and TDRD9 showed very similar localization at all ages, whereas DAZL and PIWIL4 showed specific distribution, with PIWIL4 showing shuttling from the nucleus to the cytoplasm by the end epigenetic reprogramming. In quiescent 19dpc gonocytes all proteins colocalized in a nuage adjacent to the nucleus. DAZL interacts with PIWIL4 and MAEL, suggesting that DAZL acts with these proteins to repress Line-1. TDRD9, however, does not interact with DAZL or MAEL despite their colocalization. Line-1 aggregates were detected predominantly in the nuclear periphery, although did not show homogeneous distribution as observed for the nuage. In conclusion, the nuage in quiescent rat gonocytes show a very distinguished organization that might be related to the organization of Line-1 clusters and describe the association of DAZL with proteins responsible for Line-1 repression.

Pyrrolidine Dithiocarbamate Attenuates Cardiocyte Apoptosis and Ameliorates Heart Failure Following Coronary Microembolization in Rats

Background: Nuclear factor-kB is highly activated in cardiovascular disorders. However, few articles have targeted at the role of nuclear factor-kB inhibitor in heart failure. Aims: To evaluate the effects of nuclear factor-kB inhibitor pyrrolidine dithiocarbamate on cardiocyte apoptosis and cardiac function in a rat heart failure model. Study Design: Animal experiment. Methods: A stable and reproducible rat heart failure model (n=64) was prepared by injecting homologous microthrombotic particles into the left ventricle of Sprague­Dawley rats while obstructing the ascending aorta to produce coronary microembolization. Rats with heart failure were randomized into untreated (HFu) and pyrrolidine dithiocarbamate-treated (HFp) groups; the latter received an intraperitoneal injection of pyrrolidine dithiocarbamate (100 mg/kg/day) 1 h prior to surgery as well as on postoperative days 1-7. The sham group comprised 32 Sprague­Dawley rats. Eight rats from each group were sacrificed on days 1, 3, 7, and 14 postoperatively. Masson's trichrome staining was used to determine the micro-fibrotic area to indicate the severity of myocardial loss. Terminal transferase uridine triphosphate nick end labeling staining was used to detect apoptotic cardiomyocytes. Echocardiography and hemodynamics were performed to evaluate left ventricular function. Results: Rats with heart failure exhibited pathological changes evidenced by patchy myocardial fibrosis, remarkably elevated severity of myocardial loss, and persistently reduced left ventricular function. At the end of the study, compared with the HFu group, myocardial infarct size was reduced by 28% (p=0.001), cardiocyte apoptosis was suppressed (7.17%±1.47% vs 2.83%±0.75%, p<0.001), cardiac function parameters such as left ventricular ejection fraction (80%±4% vs 61%±6%), left ventricular + dP/dt max (4828±289 vs 2918±76 mmHg.s−1), left ventricular - dP/dt max (4398±269 vs 2481±365 mmHg.s−1), and left ventricular systolic pressure (126±13 vs 100±10 mmHg) were significantly increased, and left ventricular end-diastolic pressure was reduced (18±2 vs 13±1 mmHg) (p<0.001, for all) in the HFu group. Conclusion: Our rat model can adequately mimic heart failure via coronary vessel embolization. Moreover, pyrrolidine dithiocarbamate treatment can reduce cardiocyte apoptosis and improve cardiac function, which may be beneficial for patients with heart failure secondary to myocardial infarction.

l-Methionine activates Nrf2-ARE pathway to induce endogenous antioxidant activity for depressing ROS-derived oxidative stress in growing rats.

BACKGROUND: Methionine is an essential sulfur-containing amino acid. To elucidate the influence of l-methionine on activation of the nuclear factor erythroid 2-related factor 2-antioxidant responsive element (Nrf2-ARE) antioxidant pathway to stimulate the endogenous antioxidant activity for depressing reactive oxygen species (ROS)-derived oxidative stress, male Wistar rats were orally administered l-methionine daily for 14 days. RESULTS: With the intake of l-methionine, Nrf2 was activated by l-methionine through depressing Keap1 and Cul3, resulting in upregulation of ARE-driven antioxidant expression (glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modulatory subunit, glutathione synthase (GS), catalase (CAT), superoxide dismutase (SOD), heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, glutathione reductase (GR), glutathione S-transferase (GST), glutathione peroxidase (GPx)) with increasing l-methionine availability. Upon activation of Nrf2, glutathione synthesis was increased through upregulated expression of methionine adenosyltransferase, S-adenosylhomocysteine hydrolase, cystathionine ß-synthase, cystathionine γ-lyse, glutamate cysteine ligase (GCL) and GS, while hepatic expressions of methionine sulfoxide reductases (MsrA, MsrB2, MsrB3) and hepatic enzyme activities (CAT, SOD, GCL, GR, GST, GPx) were uniformly stimulated with increasing consumption of l-methionine. As a result, hepatic content of ROS and MDA were effectively reduced by l-methionine intake. CONCLUSION: The present study demonstrates that methionine availability plays a critical role in activation of the Nrf2-ARE pathway to induce an endogenous antioxidant response for depressing ROS-derived oxidative stress, which is primarily attributed to the stimulation of methionine sulfoxide reductase expression and glutathione synthesis. © 2019 Society of Chemical Industry.

Role of Theobromine in Cocoa's Metabolic Properties in Healthy Rats.

Cocoa is rich in polyphenols and methylxanthines, and it has been reported that its consumption, among other properties, has beneficial effects on metabolism. This study aimed to investigate the role of theobromine in cocoa's metabolic properties in healthy rats. In addition to morphometric measurements, biochemical markers of lipids and glucose metabolism and gene expression of molecules related to immune cells in adipose and hepatic tissues were assessed after 7 or 18 days of diet. Additionally, a metabolomic analysis was carried out at day 7. This study revealed the presence of six discriminant metabolites in plasma due to the diets. Moreover, the results showed that theobromine is the main responsible factor for cocoa's effects on body weight gain as well as on lipid and glucose metabolism. The effects on body weight and lipids appeared as early as after 7 days of diet, whereas those affecting glucose metabolism required a longer intervention.

Species differences in lipoprotein lipase and hepatic lipase activities: comparative studies of animal models of lifestyle-related diseases.

Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) have an important role in lifestyle-related diseases. To evaluate species differences, we compared LPL and HTGL activities in different animal models of lifestyle-related diseases using the same assay kit. Normal animals (JW rabbits, ICR mice, and SD rats), a hypercholesterolemic animal model (WHHLMI rabbits), and obese animal models (KK-Ay mice and Zucker fatty rats) fed standard chow were used in this study. Plasma was prepared before and after an intravenous injection of heparin sodium under fasting and feeding. LPL and HTGL activities were measured with the LPL/HTGL activity assay kit (Immuno-Biological Laboratories) using an auto-analyzer. Only in mice, high HTGL activity was observed in pre-heparin plasma. In normal animals, LPL and HTGL activities were high in ICR mice and SD rats but low in JW rabbits. Compared to normal animals, LPL activity was high in Zucker fatty rats and WHHLMI rabbits at both fasting and feeding, while LPL activity after feeding was low in KK-Ay mice. HTGL activity was higher in fasted and fed WHHLMI rabbits and fasted Zucker fatty rats, but was lower in fed KK-Ay mice. Gender difference was observed in HTGL activity in SD rats and LPL activity in WHHLMI rabbits but not in ICR mice. In conclusion, this simple assay method was effective for measuring LPL and HTGL activities of experimental animals, and the activities are highly regulated depending on animal species, animal models, feeding/fasting conditions and genders.

Cross-species comparison of the metabolism and excretion of selexipag.

1. The metabolism of the prostacyclin receptor agonist selexipag (NS-304; ACT-293987) and its active metabolite MRE-269 (ACT-333679) has been investigated in liver microsomes and hepatocytes of rats, dogs, and monkeys. MRE-269 formation is the main pathway of selexipag metabolism, irrespective of species. Some interspecies differences were evident for both compounds in terms of both metabolic turnover and metabolic profiles. The metabolism of MRE-269 was slower than that of selexipag in all three species. 2. The metabolism of selexipag was also studied in bile-duct-cannulated rats and dogs after a single oral and intravenous dose of [14C]selexipag. MRE-269 acyl glucuronide was found in both rat and dog bile. Internal acyl migration reactions of MRE-269 glucuronide were identified in an experiment with the synthetic standard MRE-6001. 3. MRE-269 was the major component in the faeces of rats and dogs. In ex vivo study using rat and dog faeces, selexipag hydrolysis to MRE-269 by the intestinal microflora is considered to be a contributory factor in rats and dogs. 4. A taurine conjugate of MRE-269 was identified in rat bile sample. Overall, selexipag was eliminated via multiple routes in animals, including hydrolysis, oxidative metabolism, conjugation, intestinal deconjugation, and gut flora metabolism.

Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism.

In eukaryotes, almost all RNA species are processed at their 3' ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases. In recent years, several terminal nucleotidyl transferases (TENTs) including non-canonical poly(A) polymerases (ncPAPs) and terminal uridyl transferases (TUTases) have been discovered. In contrast to canonical polymerases, TENTs' functions are more diverse; some, especially TUTases, induce RNA decay while others, such as cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. The mammalian genome encodes 11 different TENTs. This review summarizes the current knowledge about the functions and mechanisms of action of these enzymes.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.