Atorvastatin attenuates intestinal mucositis induced by 5-fluorouracil in mice by modulating the epithelial barrier and inflammatory response.

Chemotherapy-induced intestinal mucositis is a major side effect of cancer treatment. Statins are 3-hydroxy-3-methyl glutaryl coenzyme reductase inhibitors used to treat hypercholesterolemia and atherosclerotic diseases. Recent studies have demonstrated that atorvastatin (ATV) has antioxidant, anti-inflammatory, and resulting from the regulation of different molecular pathways. In the present study, we investigated the effects of ATV on intestinal homeostasis in 5-fluorouracil (5-FU)-induced mucositis. Our results showed that ATV protected the intestinal mucosa from epithelial damage caused by 5-FU mainly due to inflammatory infiltrate and intestinal permeability reduction, downregulation of inflammatory markers, such as Tlr4, MyD88, NF-κB, Tnf-a, Il1ß, and Il6 dose-dependent. ATV also improved epithelial barrier function by upregulating the mRNA transcript levels of mucin 2 (MUC2), and ZO-1 and occludin tight junction proteins. The results suggest that the ATV anti-inflammatory and protective effects on 5-FU-induced mice mucositis involve the inhibition of the TLR4/MYD88/NPRL3/NF-κB, iNos, and caspase 3.

Higher atherogenic risk in schoolchildren is associated with MTMR9 rs2293855 gene polymorphism and genetic score.

Childhood dyslipidaemia is associated with the occurrence of cardiovascular diseases in adulthood, so evaluating whether an individual has a genetic predisposition to this pathology is of great importance for early action of prevention and treatment. This study aimed to evaluate the association between the FTO (rs9939609), MC4R (rs17782313) and MTMR9 (rs2293855) polymorphisms, the obesity-related genetic risk score and atherogenic risk in Brazilian children. This is a cross-sectional study conducted in 544 children aged 4-9 years in the city of Viçosa, Minas Gerais state, Brazil. The single nucleotide polymorphisms rs9939609, rs17782313 and rs2293855, were identified by the system TaqMan SNP genotyping and the obesity-related genetic risk score was determined. The lipid profile (serum total cholesterol [TC], high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol, triglycerides) was analysed and the atherogenic indices (Castelli I and II indices), atherogenic coefficient (AC), lipoprotein combined index (LCI) and plasma atherogenic index (PAI) were calculated. A semi-structured questionnaire was applied, obtaining data on the sociodemographic, economic and lifestyle characteristics of the children. Weight and height measurements were performed in all children, and body composition was evaluated by Dual-Energy X-ray Absorptiometry (DXA). 55.5% of the sample had dyslipidaemia, while 28.5% of the sample had at least one polymorphism and 2.2% had three polymorphisms. Children with the AG/AA genotypes in the rs2293855 polymorphism had lower HDL cholesterol levels and higher TC/HDL cholesterol, LDL/HDL cholesterol ratios and AC. Those with one or more polymorphisms (rs9939609, rs17782313 and rs2293855) in the genetic risk score had lower HDL cholesterol levels and higher TC/HDL cholesterol ratios, AC, LCI and PAI. In conclusion, the risk allele of the rs2293855 polymorphism and a higher obesity-related genetic risk score were positively associated with higher atherogenic risk in Brazilian children.

The atheroprotective role of fucoidan involves the reduction of foam cell formation by altering cholesterol flux-associated factors in macrophages.

Atherosclerosis is characterized by the accumulation of lipid-laden cells in the arterial walls, resulting from dysregulation of cholesterol homeostasis in the macrophage, triggered by oxidized low-density lipoprotein (oxLDL). Previous studies have shown that fucoidan, a sulfated polysaccharide from brown seaweeds, has several atheroprotective activities, however, the mechanism of fucoidan protection is not fully understood. Thus, we investigated the effect of fucoidan on atherogenesis in apolipoprotein E-deficient (ApoE-/-) mice, on oxLDL uptake by macrophages, and on the expression of the flux-associated scavenger receptors by macrophages. Also, we examined the absorption and biodistribution of orally administered fucoidan. ApoE-/- mice fed on a cholesterol-rich diet supplemented with 1% fucoidan showed reduced dyslipidemia and atherosclerosis. Fucoidan was detected in blood and peripheral tissue after gavage, suggesting that it can exert direct systemic effects. In vitro, fucoidan reduced macrophage oxLDL uptake, which resulted in lower foam cell formation. This effect was associated with downregulation of the cholesterol influx-associated scavenger receptor (SR)-A expression, and upregulation of the cholesterol efflux-associated SR-B1 expression. In conclusion, fucoidan prevented oxLDL-mediated foam cell formation in macrophages by downregulating SR-A1/2 and by up-regulating SR-B1.

Lower paraoxonase 1 paraoxonase activity is associated with a worse prognosis in patients with non-ST-segment elevation myocardial infarction in long-term follow-up.

BACKGROUND: Acute coronary syndrome (ACS) is one of the main manifestations of coronary artery disease, with a higher prevalence and worst prognosis. Oxidative stress is important in atherosclerosis and ACS, and paraoxonase 1 (PON1) is directly related to reducing the effects of oxidative stress on lipoproteins. The present study evaluated the prognostic value of PON1 activity in patients with non-ST-segment elevation ACS [non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina (UA)], included in the ERICO study. METHODS: PON1 paraoxonase activity was determined in serum samples from 485 patients collected on admission. The prognostic value in the follow-up of up to 5 years was evaluated according to cutoff points established by tertiles. Kaplan-Meier curves and Cox regression were used for the analysis of all-cause mortality and cardiovascular mortality. RESULTS: The sample consisted mainly of elderly patients with a high frequency of cardiovascular risk factors. At follow-up of up to 5 years, there were 126 deaths from all causes (80 deaths from CVD). The lowest tertile of PON1 paraoxonase activity was associated with a higher risk of death in patients with NSTEMI, but not in patients with UA. CONCLUSION: PON1 paraoxonase activity has potential prognostic value in patients with NSTEMI.

OxLDL induces membrane structure rearrangement leading to biomechanics alteration and migration deficiency in macrophage.

Cholesterol sequestration from plasma membrane has been shown to induce lipid packing disruption, causing actin cytoskeleton reorganization and polymerization, increasing cell stiffness and inducing lysosomal exocytosis in non-professional phagocytes. Similarly, oxidized form of low-density lipoprotein (oxLDL) has also been shown to disrupt lipid organization and packing in endothelial cells, leading to biomechanics alterations that interfere with membrane injury and repair. For macrophages, much is known about oxLDL effects in cell activation, cytokine production and foam cell formation. However, little is known about its impact in the organization of macrophage membrane structured domains and cellular mechanics, the focus of the present study. Treatment of bone marrow-derived macrophages (BMDM) with oxLDL not only altered membrane structure, and potentially the distribution of raft domains, but also induced actin rearrangement, diffuse integrin distribution and cell shrinkage, similarly to observed upon treatment of these cells with MßCD. Those alterations led to decreased migration efficiency. For both treatments, higher co-localization of actin cytoskeleton and GM1 was observed, indicating a similar mechanism of action involving raft-like domain dynamics. Lastly, like MßCD treatment, oxLDL also induced lysosomal spreading in BMDM. We propose that OxLDL induced re-organization of membrane/cytoskeleton complex in macrophages can be attributed to the insertion of oxysterols into the membrane, which lead to changes in lipid organization and disruption of membrane structure, similar to the effect of cholesterol depletion by MßCD treatment. These results indicate that oxLDL can induce physical alterations in the complex membrane/cytoskeleton of macrophages, leading to significant biomechanical changes that compromise cell behavior.

Protease-activated receptor 2 enhances innate and inflammatory mechanisms induced by lipopolysaccharide in macrophages from C57BL/6 mice.

OBJECTIVE: This study was conducted to investigate the effects of the synthetic PAR2 agonist peptide (PAR2-AP) SLIGRL-NH2 on LPS-induced inflammatory mechanisms in peritoneal macrophages. METHODS: Peritoneal macrophages obtained from C57BL/6 mice were incubated with PAR2-AP and/or LPS, and the phagocytosis of zymosan fluorescein isothiocyanate (FITC) particles; nitric oxide (NO), reactive oxygen species (ROS), and cytokine production; and inducible NO synthase (iNOS) expression in macrophages co-cultured with PAR-2-AP/LPS were evaluated. RESULTS: Co-incubation of macrophages with PAR2AP (30 µM)/LPS (100 ng/mL) enhanced LPS-induced phagocytosis; production of NO, ROS, and the pro-inflammatory cytokines interleukin (IL)-1ß, tumour necrosis factor (TNF)-α, IL-6, and C-C motif chemokine ligand (CCL)2; and iNOS expression and impaired the release of the anti-inflammatory cytokine IL-10 after 4 h of co-stimulation. In addition, PAR2AP increased the LPS-induced translocation of the p65 subunit of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) and reduced the expression of inhibitor of NF-κB. CONCLUSION: This study provides evidence of a role for PAR2 in macrophage response triggered by LPS enhancing the phagocytic activity and NO, ROS, and cytokine production, resulting in the initial and adequate macrophage response required for their innate response mechanisms.

Gluten-Free Diet Reduces Diet Quality and Increases Inflammatory Potential in Non-Celiac Healthy Women.

AIM: Gluten-free diets (GFDs) have gained popularity in the general population. Nonetheless, controlled studies are necessary before decisions can be made to promote GFDs. We aimed to evaluate the effects of gluten intake on body weight, body composition, and resting energy expenditure and observe the changes in nutrient intake caused by GFDs. METHODS: Twenty-three women were kept on a GFD for six weeks and received muffins with 20 g of gluten isolate (gluten period) or muffins without gluten (gluten-free period) in a crossover, single-blind, non-randomized trial. Gastrointestinal symptoms, food frequency questionnaires, body composition, and resting energy expenditure were assessed before the study (habitual or usual diet) and in the third and sixth weeks. Food intake was recorded daily for six weeks. RESULTS: Gastrointestinal symptoms, resting energy expenditure, and body weight and composition were similar during the gluten period and gluten-free period. When the diet of the gluten-free period was compared with the habitual diet, we found an increase in the intake of fat and sodium and a reduction in the intake of fiber and vitamins B1, B6, B12, and folate. The nutrient imbalance caused by a GFD led to an increase in the dietary inflammatory index, thus suggesting that this type of diet has high inflammatory potential. CONCLUSION: Gluten intake (20 g/day) did not alter body composition and resting energy expenditure in healthy women without caloric restriction in the diet for a short period (three weeks). However, a GFD led to changes in the composition of the diet, which worsened the quality of the diet and increased its inflammatory potential.

Eating in the Amazon: Nutritional Status of the Riverine Populations and Possible Nudge Interventions.

The Amazon is the largest tropical forest in the world and a source of healthy food, such as fruits and fish. Surprisingly, the Amazonian riverine population present an increased prevalence (as high as 58%) of non-communicable diseases, such as hypertension and insulin resistance, even higher than that described for the urban population of the Amazon. Therefore, this work aimed to analyze the nutritional status and associated risk of the riverine population. Body mass index, waist circumference (WC), waist-to-hip ratio, and neck circumference (NC) were evaluated, and risk analysis was assayed. Furthermore, data about occupation and the prevalence of consumers of the different groups of food were analyzed. All anthropometric parameters revealed high proportions of individuals at risk, WC and NC being the factors that had more high-risk women and men, respectively. Our data confirmed the characteristic profile of the riverine communities with a high number of fish consumers, but also observed different patterns probably associated to a phenomenon of nutrition transition. Based on our data, some nudge interventions that take into account the principles of behavior analysis are discussed and proposed for these populations, aiming to improve the nutritional status and avoid the long-term consequences of the results showed by this work.

Melatonin administration attenuates acute stress by inducing sleep state in zebrafish (Danio rerio).

Melatonin plays a fundamental homeostatic role in basic biological functions, and an anti-stress role has been also proposed for this hormone. This study aimed to evaluate hormonal, enzymatic and behavioral parameters of zebrafish that received administration of melatonin and were submitted to acute stress. A total of 120 wild-type zebrafish were divided into five groups: naïve control (N), negative control group (Stress/C), positive control treated with diazepam (Stress/Diaz), treatment with melatonin at dose 1 (Stress/Melt. 1) and treatment with melatonin at dose 2 (Stress/Melt. 2). The exposure to treatments (diazepam or melatonin) was performed prior to the acute stress protocol, based on a chase by a fishing net during 5 min followed by exposure to the air for 1 min. The body cortisol levels were assessed, as well as oxidative stress (thiobarbituric acid reactive substances, reactive species of oxygen and antioxidant activity), and fish behavior (open field test). Melatonin was able to modulate acute stress effects on zebrafish by inhibiting cortisol increasing levels, reducing locomotor parameters, inducing a sleep state, reducing lipid peroxidation and stimulating antioxidant enzymatic activity.

Prophylactic and therapeutic supplementation using fructo-oligosaccharide improves the intestinal homeostasis after mucositis induced by 5- fluorouracil.

The beneficial effects of prebiotic, such as fructo-oligosaccharides (FOS), in intestinal inflammation have been demonstrated in several studies. Herein, we evaluate whether joint treatment with FOS, both before and during mucositis, had additional beneficial effects and investigated the mechanisms underlying in the action of FOS on the intestinal barrier. BALB/c mice were randomly divided into five groups: CTR (without mucositis + saline solution), FOS (without mucositis + 6 % FOS), MUC (mucositis + saline solution), PT (mucositis + 6 % FOS supplementation before disease induction), and TT (mucositis + 6 % FOS supplementation before and during disease induction). Mucositis was induced by intraperitoneal injection (300 mg/kg) of 5-fluorouracil (5-FU). After 72 h, the animals were euthanized and intestinal permeability (IP), tight junction, bacterial translocation (BT), histology and morphometry, and immunoglobulin A secretory (sIgA), inflammatory infiltrate, and production of short-chain fatty acids (acetate, butyrate and propionate) were evaluated. The MUC group showed an increase in the IP, BT, and inflammatory infiltrate but a decrease in the tight junction expression and butyrate and propionate levels (P < 0.05). In the PT and TT groups, FOS supplementation maintained the IP, tight junction expression, and propionate concentration within physiologic levels, increased butyrate levels, and reduced BT and inflammatory infiltrate (P < 0.05). Total treatment with FOS (TT group) was more effective in maintaining histological score, morphometric parameters, and sIgA production. Thus, total treatment (prophylactic and therapeutic supplementation) with FOS was more effective than pretreatment alone, in reducing 5-FU-induced damage to the intestinal barrier.

d-Limonene Ameliorates Myocardial Infarction Injury by Reducing Reactive Oxygen Species and Cell Apoptosis in a Murine Model.

Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.

Antiobesity effects of anthocyanins on mitochondrial biogenesis, inflammation, and oxidative stress: A systematic review.

Studies have shown that anthocyanins attenuate obesity. In this review, we confirm these effects and explain the possible mechanisms underlying them. A systematic search was conducted in electronic databases using obesity as the main term along with anthocyanins and the main anthocyanidins, including articles in Portuguese, English, and Spanish without any restriction as to year. The review was carried out by peers following PRISMA recommendations: 1980 studies were identified, and 19 articles were analyzed. The studies varied in relation to time, pathways, cells used, and anthocyanin types. The positive effects were observed in 5' adenosine monophosphate-activated protein kinase pathways and mitochondrial biogenesis and in a reduction in inflammation and oxidative stress. Anthocyanins can improve the metabolic control involved in obesity by reducing lipogenesis, oxidative stress, and inflammation. This can boost the speed of lipolysis and thermogenesis, regulate satiety, and reduce body fat accumulation. In addition, anthocyanins have shown promising effects on controlling obesity compared with the standard of care.

The prognostic value of nitrotyrosine levels in coronary heart disease: long-term evaluation in the Acute Coronary Syndrome Registry Strategy (ERICO study).

INTRODUCTION: We aimed to analyze the association of nitrotyrosine (N-TYR) levels and long-term survival in an ongoing coronary heart disease (CHD) prospective cohort, the Acute Coronary Syndrome Registry Strategy (ERICO study). METHODS: N-TYR levels collected during acute and subacute phase from onset of acute coronary syndrome (ACS) symptoms (myocardial infarction and unstable angina) were evaluated in 342 patients. We calculated case-fatality rates (180-days, 1 year, 2 years and 4 years) and survival analyses up to 4 years using Kaplan-Meier curves and Cox regression with respective cumulative hazard ratios (95% confidence interval; 95%CI), according to N-TYR tertiles up to 4 years of follow-up. Models are presented as crude, age and sex-adjusted and further adjusted for lipids and other confounders. RESULTS: Overall, median level of N-TYR was 208.33 nmol/l (range: 3.09 to 1500 nmol/l), regardless ACS subtype. During follow-up of 4 years, we observed 44 (12.9%) deaths. Overall survival rate was 298 (87.1%) (Survival days: 1353, 95%CI: 1320-1387 days). N-TYR levels did not associate with mortality / survival rates up to 4 years. CONCLUSIONS: No relationship was found between N-TYR levels and mortality rates after ACS during 4-year follow-up in the ERICO study.

Low serum levels of CCL2 are associated with worse prognosis in patients with Acute Coronary Syndrome: 2-year survival analysis.

Inflammation is very important in Acute Coronary Syndrome (ACS) as well as in cardiac remodeling after an acute myocardial infarction (MI). Our study examined the prognostic value of Chemokine (C-C motif) ligand 2 (CCL2) in patients with ACS in the ERICO (Strategy of Registry of Acute Coronary Syndrome) study. We evaluated serum samples from 803 patients. The prognostic value of CCL2 was evaluated at the 2-year follow-up, according to cutoff points established by the median. Kaplan-Meier curves and Cox regression were used for analysis of all-cause mortality, cardiovascular mortality, and a combined outcome of fatal myocardial infarction or new non-fatal MI. There were 115 deaths from all causes, 78 deaths due to cardiovascular causes and 67 events in combined outcomes. CCL2 levels below the median (≤100.9 pg/mL) were associated with increased risk of MI death or new non-fatal MI, even after model adjustment. Low serum levels of CCL2 shows a significant association with fatal or new non-fatal MI.

Myeloperoxidase activity and acute coronary syndrome survival: long-term evaluation in the ERICO study.

AIM: We aimed to analyze the influence of myeloperoxidase (MPO) activity on mortality in the Acute Coronary Syndrome Registry Strategy (ERICO) study. METHODS: MPO activity levels were evaluated in 342 patients. We performed survival analyses using Kaplan-Meier curves and Cox regression with respective hazard ratios, 95% CI, according to MPO tertiles distribution up to 7 years of follow-up. RESULTS: Higher MPO activity levels were seen in men, smokers, diabetics and those who were taking aspirin. MPO activity levels were neither significant in relation to mortality nor to survival rates up to seven years. CONCLUSION: We found no relationship between elevated levels of MPO activity post-acute coronary syndrome and mortality up to 7-years of follow-up in the ERICO study.

Conjugated linoleic acid prevents damage caused by intestinal mucositis induced by 5-fluorouracil in an experimental model.

BACKGROUND: Studies have showed the protective effects of conjugated linoleic acid (CLA) on intestinal epithelium, modulating host immune and inflammatory responses on intestinal diseases. OBJECTIVE: To evaluate the preventive effects of CLA on the intestinal mucositis induced by 5-FU in a murine model. METHODS: Sixty-four BALB/c mice were randomly divided into four groups: Control (CTL), fed a standard chow diet; CLAs, fed a diet supplemented with CLA; Mucositis (5-FU), fed a standard chow diet and underwent mucositis induction and CLAs 5-FU, fed a diet supplemented with CLA and underwent mucositis induction. Mucositis was induced by intraperitoneal injection of 300 mg/kg 5-FU. After 72 h, the animals were euthanized and intestinal permeability, bacterial translocation, inflammatory mediators, and intestinal histology were evaluated. RESULTS: Mice in the CLAs 5-FU group showed reduced weight loss compared to those in the 5-FU group (p < 0.005). Furthermore, the results also showed that the treatment with CLA reduced intestinal permeability, bacterial translocation, and biomarkers of inflammatory response besides minor damage to ZO-1 and occludin with maintenance of the integrity of the intestinal epithelium and a favorable balance between the inflammatory and regulatory cytokines. CONCLUSION: This study suggests that CLA reduced the adverse effects from 5-FU administration on the intestinal mucosa.

The polymorphism rs17782313 near MC4R gene is related with anthropometric changes in women submitted to bariatric surgery over 60 months.

OBJECTIVE: Evaluate whether the polymorphism rs17782313 near MC4R gene influences long-term outcomes after bariatric surgery. METHODS: The rs16782313 polymorphism was genotyped in 217 individuals undergoing bariatric surgery and analyzed in detail in 141 women. Data for comorbidities, BMI, excess weight loss (EWL), and body composition were obtained before and during 60 months after surgery. RESULTS: The risk allele was found in 65 (47%) of the 141 women. Pre-surgical body weight and BMI were higher in carriers of the rs17782313 polymorphism (CC + CT group) than in non-carriers (TT group) (p = 0.039 and 0.047, respectively). The number of women who acquired surgical success (EWL > 50%), was lower in CC + CT group compared to TT group (p = 0.015). The minimum BMI seen during the 60 months of follow-up was higher in CC + CT group compared to TT group (p = 0.028). The number of women who presented BMI < 30 kg/m2 (no longer classified as obesity) after 24 months of surgery was inferior in CC + CT group (6 out 35 patients - 17%) than in TT group (19 out 49 patients - 37%, p = 0.043). Moreover, the number of patients maintaining BMI > 35 kg/m2 were higher carriers (18 out 35 patients - 51%) compare to non-carriers (16 out 49 patients - 32%, p = 0.045). CONCLUSION: Women with extreme obesity carrying rs17782313 MC4R polymorphism present a higher pre-surgical BMI, are more unlikely to reach non-obesity BMI (<30 kg/m2) and tend to maintain a BMI > 35 kg/m2 that characterize treatment failure.

Improvement of the liver pathology by the aqueous extract and the n-butanol fraction of Sida pilosa Retz in Schistosoma mansoni-infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sida pilosa Retz (Malvaceae) is a plant used in Africa for the treatment of intestinal helminthiasis, lower abdominal pains and dysmenorrhea. AIM OF THE STUDY: In order to determine the potential use of S. pilosa in the treatment of schistosomiasis mansoni, we evaluated the schistosomicidal, antioxidant and anti-fibrotic properties of the aqueous extract and the n-butanol fraction of its aerial parts. MATERIAL AND METHODS: S. pilosa aqueous extract (SpAE) at 100, 200 and 400mg/kg and n-butanol fraction (SpBF) at 50, 100 and 200mg/kg were administered per os to Schistosoma mansoni-infected mice for 4 weeks. Praziquantel (100mg/kg × 5 days) was used as reference drug. After sacrifice, worm burden and egg count, transaminases and proteins levels were evaluated. Malondialdehyde (MDA), lipid hydroperoxydes (LOOH), catalase (CAT), superoxide dismutase (SOD), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) were also measured. The anti-fibrotic effect of the plant was evaluated by the determination of hydroxyproline and γ-interferon (IFN-γ). RESULTS: The treatment of S. mansoni-infected mice by SpAE or SpBF resulted in a moderate reduction of worm burden and egg load in the liver and intestine. Both SpAE and SpBF significantly reversed the increasing liver proteins, MDA, LOOH and CAT levels induced by the infection. Moreover, SOD activity was improved by SpAE and SpBF. Schistosomiasis mansoni considerably increased the EPO (p<0.001) and MPO activities (p<0.001). SpAE treatment significantly reduced EPO and MPO activities at all doses. SpBF failed to reduce the increasing MPO and decreased EPO only at the highest dose. S. mansoni-infection induced an increase in hydroxyproline content (p<0.001) and a decrease in IFN-γ level (p<0.001). Both SpAE and SpBF significantly reduced hepatic hydroxyproline content, while only SpAE (p<0.05) improved IFN-γ level. CONCLUSION: These results suggest that the liver pathology in schistosomiasis mansoni is improved by S. pilosa aqueous extract, which disclosed a moderate schistosomicidal, but strong antioxidant and anti-fibrotic activities. The n-butanol fraction was however less active than the aqueous extract.

Arginine Supplementation Induces Arginase Activity and Inhibits TNF-α Synthesis in Mice Spleen Macrophages After Intestinal Obstruction.

BACKGROUND: The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals. MATERIAL AND METHODS: Male C57BL6/J wild-type (WT) and iNOS knockout (iNOS-/-) mice were randomized into 6 groups: Sham and Sham-/- (standard chow), IO and IO-/- (standard chow + IO), and Arg and Arg-/- (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF-α and IL-10 levels were analyzed in splenic macrophage cultures. RESULTS: Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO-/-, and Arg-/- groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF-α levels (Arg vs IO group, P < .05) and maintenance of IL-10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines (Sham-/-, IO-/-, and Arg-/- vs other, P < .05). CONCLUSIONS: Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF-α levels, which may be directly related to nitric oxide derived from arginine.