Spasmolytic Effects of Aphanizomenon Flos Aquae (AFA) Extract on the Human Colon Contractility

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin^® is an AFA extract particularly rich in β-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if β-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin^® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a β-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin^® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin^® and exogenous β-PEA, suggesting a trace-amine involvement in the Klamin^® effects. Accordingly, AphaMax^®, an AFA extract containing lesser amount of β-PEA, failed to modify colon contractility. Moreover, the Klamin^® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin^® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin^® exerts spasmolytic effects in human colon contractility through β-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.     

Soluble Fraction from Lysate of a High Concentration Multi-Strain Probiotic Formulation Inhibits TGF-β1-Induced Intestinal Fibrosis on CCD-18Co Cells

Fibrosis is a severe complication of chronic inflammatory disorders, such as inflammatory bowel disease (IBD). Current strategies are not fully effective in treating fibrosis; therefore, innovative anti-fibrotic approaches are urgently needed. TGF-β1 plays a central role in the fibrotic process by inducing myofibroblast differentiation and excessive extracellular matrix (ECM) protein deposition. Here, we explored the potential anti-fibrotic impact of two high concentration multi-strain probiotic formulations on TGF-β1-activated human intestinal colonic myofibroblast CCD-18Co. Human colonic fibroblast CCD-18Co cells were cultured in the presence of TGF-β1 to develop a fibrotic phenotype. Cell viability and growth were measured using the Trypan Blue dye exclusion test. The collagen-I, α-SMA, and pSmad2/3 expression levels were evaluated by Western blot analysis. Fibrosis markers were also analyzed by immunofluorescence and microscopy. The levels of TGF-β1 in the culture medium were assessed by ELISA. The effects of commercially available probiotic products VSL#3^® and Vivomixx^® were evaluated as the soluble fraction of bacterial lysates. The results suggested that the soluble fraction of Vivomixx^® formulation, but not VSL#3^®, was able to antagonize the pro-fibrotic effects of TGF-β1 on CCD-18Co cells, being able to prevent all of the cellular and molecular parameters that are related to the fibrotic phenotype. The mechanism underlying the observed effect appeared to be associated with inhibition of the TGF-β1/Smad signaling pathway. To our knowledge, this study provides the first experimental evidence that Vivomixx^® could be considered to be a promising candidate against intestinal fibrosis, being able to antagonize TGF-β1 pro-fibrotic effects. The differences that were observed in our fibrosis model between the two probiotics used could be attributable to the different number of strains in different proportions.     

Differential Response to Trichloroethylene-Induced Hepatosteatosis in Wild-Type and PPARα-Humanized Mice

Background

Trichloroacetic acid, an oxidative metabolite of trichloroethylene (TRI), is a ligand of the peroxisome proliferator-activated receptor α (PPAR) α, which is involved in lipid homeostasis and anti-inflammation.

Objective

We examined the role of mouse and human PPARα in TRI-induced hepatic steatosis and toxicity.

Methods

Male wild-type (mPPARα), Pparα-null, and humanized PPARα (hPPARα) mice on an Sv/129 background were exposed via inhalation to 0, 1,000, and 2,000 ppm TRI for 8 hr/day for 7 days. We assessed TRI-induced steatosis or hepatic damage through biochemical and histopathological measurements.

Results

Plasma alanine aminotransferase and aspartate aminotransferase activities increased in all mouse lines after exposure to 1,000 and 2,000 ppm TRI. Exposure induced hepatocyte necrosis and inflammatory cells in all mouse lines, but hepatic lipid accumulation was observed only in Pparα-null and hPPARα mice. No differences were observed in TRI-mediated induction of hepatic PPARα target genes except for a few genes that differed between mPPARα and hPPARα mice. However, TRI significantly increased expression of triglyceride (TG)-synthesizing enzymes, diacylglicerol acyltransferases, and PPARγ in Pparα-null and hPPARα mice, which may account for the increased TG in their livers. TRI exposure elevated nuclear factor-kappa B (NFκB) p52 mRNA and protein in all mice regardless of PPARα genotype.

Conclusions

NFκB-p52 is a candidate molecular marker for inflammation caused by TRI, and PPARα may be involved in TRI-induced hepatosteatosis. However, human PPARα may afford only weak protection against TRI-mediated effects compared with mouse PPARα.     

Vascular Effects of the Polyphenolic Nutraceutical Supplement Taurisolo®: Focus on the Protection of the Endothelial Function

Preservation of vascular endothelium integrity and functionality represents an unmet medical need. Indeed, endothelial dysfunction leads to decreased nitric oxide biosynthesis, which is prodromic of hypertension and hypercoagulability. In this panorama, the nutraceutical supplement Taurisolo^®, a polyphenolic extract from Aglianico cultivar grape, rich in catechin and procyanidins, was evaluated as a vasoprotective, vasorelaxing, anti-hypertensive and anti-coagulant agent in: cell lines, isolated vessels, in vivo models of chronic hypertension and hypercoagulability, and in clinical tests of endothelial reactivity. Taurisolo^® demonstrated to fully protect vascular cell viability from oxidative stimulus at 100 µg/mL and evoke vasorelaxing effects (Emax = 80.6% ± 1.9 and pEC50 = 1.19 ± 0.03) by activation of the Sirtuins-AMPK-pathway. Moreover, Taurisolo^®, chronically administered at 20 mg/Kg/die in in vivo experiments, inhibited the onset of cardiac hypertrophy (heart weight/rat weight = 3.96 ± 0.09 vs. 4.30 ± 0.03), hypercoagulability (decrease of fibrinogen vs. control: p < 0.01) and hypertension (mean of Psys: 200 ± 2 vs. control 234 ± 2 mmHg) and improved endothelial function (Emax = 88.9% ± 1.5 vs. control 59.6% ± 3.6; flow-mediated dilation in healthy volunteers after 400 mg twice daily for 8 weeks vs. baseline: p = 0.019). In conclusion, Taurisolo^® preserves the vascular function against ox-inflamm-ageing process and the consequent cardiovascular accidents.     

Effect and Tolerability of a Nutritional Supplement Based on a Synergistic Combination of β-Glucans and Selenium- and Zinc-Enriched Saccharomyces cerevisiae (ABB C1®) in Volunteers Receiving the Influenza or the COVID-19 Vaccine: A Randomized,Double-Blind,Placebo-Controlled Study

A single-center, randomized, double-blind, placebo-controlled study was conducted in 72 volunteers who received a synergistic combination of yeast-based ingredients with a unique β-1,3/1,6-glucan complex and a consortium of heat-treated probiotic Saccharomyces cerevisiae rich in selenium and zinc (ABB C1^®) or placebo on the next day after getting vaccinated against influenza (Chiromas^®) (n = 34) or the COVID-19 (Comirnaty^®) (n = 38). The duration of treatment was 30 and 35 days for the influenza and COVID-19 vaccine groups, respectively. Mean levels of CD4+T cells increased from 910.7 at baseline to 1000.2 cells/µL after the second dose of the COVID-19 vaccine in the ABB C1^® group, whereas there was a decrease from 1055.1 to 929.8 cells/µL in the placebo group. Changes of CD3+T and CD8+T lymphocytes showed a similar trend. In the COVID-19 cohort, the increases in both IgG and IgM were higher in the ABB C1^® supplement than in the placebo group. Serum levels of selenium and zinc showed a higher increase in subjects treated with the active product than in those receiving placebo. No serious adverse events related to ABB C1^® or tolerance issues were reported. The study findings validate the capacity of the ABB C1^® product to stimulate trained immunity.     

Effect of Omega-3 Supplementation on Self-Regulation in Typically Developing Preschool-Aged Children: Results of the Omega Kid Pilot Study—A Randomised,Double-Blind,Placebo-Controlled Trial

Supplementation of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) may enhance self-regulation (SR) and executive functioning (EF) in children of preschool age. The aim of the Omega Kid Study was to investigate the effect of n-3 LCPUFA supplementation on SR and EF in typically developing preschool-aged children. A double-blind placebo-controlled pilot trial was undertaken, the intervention was 12 weeks and consisted of 1.6 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day compared to placebo. The HS-Omega-3 Index^® was assessed by capillary blood samples at baseline and post-intervention. Seventy-eight children were enrolled and randomised to either the n-3 LCPUFA treatment (n = 39) or placebo (n = 39) group. Post intervention, there was a significant three-fold increase in the HS-Omega-3 Index^® in the n-3 LCPUFA group (p < 0.001). There were no improvements in SR or EF outcome variables for the n-3 LCPUFA group post intervention compared to the placebo group determined by linear mixed models. At baseline, there were significant modest positive Spearman correlations found between the HS-Omega-3 index^® and both behavioural self-regulation and cognitive self-regulation (r = 0.287, p = 0.015 and r = 0.242, p = 0.015 respectively). Although no treatment effects were found in typically developing children, further research is required to target children with sub-optimal self-regulation who may benefit most from n-3 LCPUFA supplementation.     

Efficacy of a Multi-Strain Probiotic Formulation in Pediatric Populations: A Comprehensive Review of Clinical Studies

A probiotic formulation combining Lactobacillus helveticus Rosell^®-52, Bifidobacterium infantis Rosell^®-33, and Bifidobacterium bifidum Rosell^®-71 with fructooligosaccharides, first commercialized in China, has been sold in over 28 countries since 2002. Clinical studies with this blend of strains were conducted mainly in pediatric populations, and most were published in non-English journals. This comprehensive review summarizes the clinical studies in infants and children to evaluate the efficacy of this probiotic for pediatric indications. Literature searches for pediatric studies on Biostime^® or Probiokid^® (non-commercial name) in 6 international and Chinese databases identified 28 studies, which were classified by indications. Twelve studies show that the probiotic significantly increases the efficacy of standard diarrhea treatment regardless of etiology, reducing the risk of unresolved diarrhea (RR 0.31 [0.23; 0.42]; p < 0.0001) by 69%. In eight studies, the probiotic enhanced immune defenses, assessed by levels of various immune competence and mucosal immunity markers (six studies), and reduced the incidence of common infections (two studies). The probiotic improved iron deficiency anemia treatment efficacy (three studies), reducing the risk of unresolved anemia by 49% (RR 0.51 [0.28; 0.92]; p = 0.0263) and significantly reducing treatment side effects by 47% (RR 0.53 [0.37; 0.77]; p = 0.0009). Other studies support further investigation into this probiotic for oral candidiasis, eczema, feeding intolerance in premature babies, or hyperbilirubinemia in newborns.     

Efficacy and Safety of Armolipid Plus®: An Updated PRISMA Compliant Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials

Armolipid Plus^® is a multi-constituent nutraceutical that claims to improve lipid profiles. The aim of this PRISMA compliant systematic review and meta-analysis was to globally evaluate the efficacy and safety of Armolipid Plus^® on the basis of the available randomized, blinded, controlled clinical trials (RCTs). A systematic literature search in several databases was conducted in order to identify RCTs assessing the efficacy and safety of dietary supplementation with Armolipid Plus^®. Two review authors independently identified 12 eligible studies (1050 included subjects overall) and extracted data on study characteristics, methods, and outcomes. Meta-analysis of the data suggested that dietary supplementation with Armolipid Plus^® exerted a significant effect on body mass index (mean difference (MD) = −0.25 kg/m², p = 0.008) and serum levels of total cholesterol (MD = −25.07 mg/dL, p < 0.001), triglycerides (MD = −11.47 mg/dL, p < 0.001), high-density lipoprotein cholesterol (MD = 1.84 mg/dL, p < 0.001), low-density lipoprotein cholesterol (MD = −26.67 mg/dL, p < 0.001), high sensitivity C reactive protein (hs-CRP, MD = −0.61 mg/L, p = 0.022), and fasting glucose (MD = −3.52 mg/dL, p < 0.001). Armolipid Plus^® was well tolerated. This meta-analysis demonstrates that dietary supplementation with Armolipid Plus^® is associated with clinically meaningful improvements in serum lipids, glucose, and hs-CRP. These changes are consistent with improved cardiometabolic health.     

Transport of Dietary Anti-Inflammatory Peptide, γ-Glutamyl Valine (γ-EV), across the Intestinal Caco-2 Monolayer

The present study analyzed the transepithelial transport of the dietary anti-inflammatory peptide, γ-glutamyl valine (γ-EV). γ-EV is naturally found in dry edible beans. Our previous study demonstrated the anti-inflammatory potency of γ-EV against vascular inflammation at a concentration of 1mM, and that it can transport with the apparent permeability coefficient (P_app) of 1.56 × 10⁻⁶ ± 0.7 × 10⁻⁶ cm/s across the intestinal Caco-2 cells. The purpose of the current study was to explore whether the permeability of the peptide could be enhanced and to elucidate the mechanism of transport of γ-EV across Caco-2 cells. The initial results indicated that γ-EV was nontoxic to the Caco-2 cells up to 5 mM concentration and could be transported across the intestinal cells intact. During apical-to-basolateral transport, a higher peptide dose (5 mM) significantly (p < 0.01) enhanced the transport rate to 2.5 × 10⁻⁶ ± 0.6 × 10⁻⁶ cm/s. Cytochalasin-D disintegrated the tight-junction proteins of the Caco-2 monolayer and increased the P_app of γ-EV to 4.36 × 10⁻⁶ ± 0.16 × 10⁻⁶ cm/s (p < 0.001), while theaflavin 3′-gallate and Gly-Sar significantly decreased the P_app (p < 0.05), with wortmannin having no effects on the peptide transport, indicating that the transport route of γ-EV could be via both PepT1-mediated and paracellular.     

Dietary Zinc Deficiency Affects Blood Linoleic Acid: Dihomo-γ-linolenic Acid (LA:DGLA) Ratio; a Sensitive Physiological Marker of Zinc Status in Vivo (Gallus gallus)

Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn(+) (zinc adequate control, 42.3 μg/g zinc), and Zn(−) (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn(+) control versus Zn(−) group (p < 0.05). Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn(+) control group (p < 0.05), and hepatic Δ⁶ desaturase was significantly higher in the Zn(+) group (p < 0.001). The LA:DGLA ratio was significantly elevated in the Zn(−) group compared to the Zn(+) group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001). This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation.     

A Multi-Mineral Intervention to Modulate Colonic Mucosal Protein Profile: Results from a 90-Day Trial in Human Subjects

The overall goal of this study was to determine whether Aquamin^®, a calcium-, magnesium-, trace element-rich, red algae-derived natural product, would alter the expression of proteins involved in growth-regulation and differentiation in colon. Thirty healthy human subjects (at risk for colorectal cancer) were enrolled in a three-arm, 90-day interventional trial. Aquamin^® was compared to calcium alone and placebo. Before and after the interventional period, colonic biopsies were obtained. Biopsies were evaluated by immunohistology for expression of Ki67 (proliferation marker) and for CK20 and p21 (differentiation markers). Tandem mass tag-mass spectrometry-based detection was used to assess levels of multiple proteins. As compared to placebo or calcium, Aquamin^® reduced the level of Ki67 expression and slightly increased CK20 expression. Increased p21 expression was observed with both calcium and Aquamin^®. In proteomic screen, Aquamin^® treatment resulted in many more proteins being upregulated (including pro-apoptotic, cytokeratins, cell–cell adhesion molecules, and components of the basement membrane) or downregulated (proliferation and nucleic acid metabolism) than placebo. Calcium alone also altered the expression of many of the same proteins but not to the same extent as Aquamin^®. We conclude that daily Aquamin^® ingestion alters protein expression profile in the colon that could be beneficial to colonic health.     

Perioperative Immunonutrition in Well-Nourished Patients Undergoing Surgery for Head and Neck Cancer: Evaluation of Inflammatory and Immunologic Outcomes

Limited work is available on the benefits of nutritional support enriched with arginine and n-3 fatty acids in surgical patients with head and neck cancer, particularly if well-nourished. We conducted a pilot study in these patients to examine effects on inflammatory markers and clinical outcome. Patients scheduled for radical resection of the oral cavity were randomised to 5 day preoperative and 5 day postoperative Impact^® (IMN, n = 4), or no preoperative supplementary nutrition and Isosource^® postoperatively (STD, n = 4). Plasma fatty acids, C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were measured at baseline, day of surgery and on postoperative days (POD) 2, 4 and 10. Postoperative complications were recorded. The (eicosapentaenoic acid plus docosahexaenoic acid) to arachidonic acid ratio was significantly higher in IMN patients on POD 2, 4 and 10 (P < 0.01). While not statistically significant, CRP, TNF-α, and IL-6 concentrations were higher in the STD group on POD2 while IL-10 was lower. Median length of stay was 10 (range 10–43) days in the IMN group and 21.5 (7–24) days in the STD group. Five complications were seen in the STD group and two in the IMN group. The results support the need for a larger trial focusing on clinical outcome.     

Association of TNF-α 308?G/A Polymorphism With Type 2 Diabetes: A Case–Control Study in the Iranian Kurdish Ethnic Group

Objectives

Tumor necrosis factor-α (TNF-α) plays roles in the development of obesity, insulin resistance, and possibility of Type 2 diabetes mellitus (T2DM). The objective of the current study was to evaluate the association of TNF-α promoter−308 G/A polymorphism with T2DM.

Methods

In all, 1038 patients with T2DM and 1023 normoglycemic controls were included in this study. All participants were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies were then analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostatic model assessment of insulin resistance, and hemoglogin A1c levels were determined by conventional methods.

Results

The allelic frequency of the A allele was significantly different between case and control participants (p = 0.006). Genotypes GA and AA were found to be significantly associated with 2.24- and 3.18-fold increased risk for T2DM, respectively. Similarly, the dominant model of -308 G/A polymorphism was found to have a higher risk for T2DM (odds ratio = 2.34, p = 0.001). Individuals with T2DM carrying the GA + AA genotypes of -308 G/A variation had significantly lower fasting plasma insulin than those carrying GG genotype.

Conclusion

Our findings revealed that there is an association between the TNF-α promoter -308 G/A polymorphism and T2DM in this population.     

Vitamin E status of 20- to 59-year-old adults living in the Seoul metropolitan area of South Korea

BACKGROUND/OBJECTIVES

Vitamin E is a fat-soluble vitamin and functions primarily as a lipid antioxidant. Inadequate vitamin E status may increase risk of several chronic diseases. Thus, the objectives of this study were to estimate intake and plasma concentration of each tocopherol and to evaluate vitamin E status of Korean adults.

SUBJECTS/METHODS

Three consecutive 24-h food recalls and fasting blood samples were collected from healthy 20- to 59-y-old adults (33 males and 73 females) living in the Seoul metropolitan area, South Korea. α-, β-, δ-, and γ-tocopherol intakes and plasma concentrations of tocopherols (α-, δ-, and γ-tocopherol) were analyzed by gender.

RESULTS

Dietary vitamin E and total vitamin E intake (dietary plus supplemental vitamin E) was 17.68 ± 14.34 and 19.55 ± 15.78 mg α-tocopherol equivalents, respectively. The mean daily α-tocopherol, and γ-tocopherol intakes were 3.07 ± 2.27 mg and 5.98 ± 3.74 mg, respectively. Intakes of total vitamin E and each tocopherol of males were significantly higher than those of females (P < 0.05). Plasma α-tocopherol concentration was 15.45 ± 10.16 of males and 15.00 ± 4.54 µmol/L of females, respectively. There were no significant differences in plasma tocopherol concentrations by gender (P ≥ 0.05). Plasma α-tocopherol was negatively correlated with γ-tocopherol intake (P < 0.05). Twenty-three percent of the subjects had plasma α-tocopherol concentrations < 12 µmol/L indicating a biochemical deficiency of vitamin E. Approximately 8% and 9% of these participants had plasma α-tocopherol:total lipid ratio less than 1.59 µmol/mmol and plasma α-tocopherol:total cholesterol ratio less than 2.22 µmol/mmol, respectively, which are also indicative of vitamin E deficiency.

CONCLUSIONS

Vitamin E intakes of Korean adults were generally adequate with the Korean Dietary Reference Intakes for vitamin E. However, α-tocopherol intake was lower than that reported in other countries, and 23% of the subjects in the current study were vitamin E deficient based on plasma α-tocopherol concentrations.     

Efficacy of a Low-Dose Diosmin Therapy on Improving Symptoms and Quality of Life in Patients with Chronic Venous Disease: Randomized,Double-Blind,Placebo-Controlled Trial

Chronic Venous Disease (CVD) is a common medical condition affecting up to 80% of the general population. Clinical manifestations can range from mild to more severe signs and symptoms that contribute to the impairment of the quality of life (QoL) of affected patients. Among treatment options, venoactive drugs such as diosmin are widely used in the symptomatic treatment in all clinical stages. The aim of this study is to determine the effectiveness of a new formulated diosmin in relieving symptoms and improving QoL in patients suffering from CVD. In this randomized, double-blind, placebo-controlled, multicenter clinical study, CVD patients with a Clinical-Etiology-Anatomy-Pathophysiology (CEAP) classification system between C2 and C4 were randomized to receive a bioavailable diosmin (as μsmin^® Plus) 450 mg tablet once daily or a placebo for 8 weeks. Clinical symptoms and QoL were monitored using the measurement of leg circumference, visual analogue scale (VAS) for pain, Global Index Score (GIS) and Venous Clinical Severity Score (VCSS). A total of 72 subjects completed the study. From week 4, leg edema was significantly decreased in the active group (p < 0.001). An improvement in the VAS score was observed in the active group compared to placebo at the end of treatment (p < 0.05). GIS and VCSS scores were significantly improved in the active group at week 8 (p < 0.001). No treatment related-side effects were recorded. The results of this study showed that the administration of low-dose μsmin^® Plus was safe and effective in relieving symptoms and improving QoL in subjects with CVD.     

The Mechanisms of the Anti-Inflammatory and Anti-Apoptotic Effects of Omega-3 Polyunsaturated Fatty Acids during Methotrexate-Induced Intestinal Damage in Cell Line and in a Rat Model

Background: The aim of this study was to examine the anti-inflammatory and anti-apoptotic patterns of omega-3 polyunsaturated fatty acids (n-3 PUFAs) during methotrexate (MTX) induced intestinal damage in cell culture and in a rat model. Methods: Non-treated and treated with MTX HT 29 and HCT116cells were exposed to increasing doses of n-3 PUFAs and cell viability was evaluated using PrestoBlue^® assay. Male Sprague-Dawley rats were divided into 4 experimental groups: Control rats, CONTR+n-3 PUFA rats that were treated with oral n-3 PUFA, MTX rats were treated with MTX given IP, and MTX+n-3 PUFA rats were treated with oral n-3 PUFA before and following injection of MTX. Intestinal mucosal parameters and mucosal inflammation, enterocyte proliferation and apoptosis, TNF-α in mucosal tissue and plasma (ELISA), NF-κB, COX-2, TNF-α, Fas, FasL, Fadd, Bid, Bax and Bcl-2gene and protein levels were determined 72 h following MTX injection. Results: Exposure of HT 29 and HCT116cells to n-3 PUFA attenuated inhibiting effects of MTX on cell viability. MTX-n-3 PUFA rats demonstrated a lower intestinal injury score and enhanced intestinal repair. A significant decrease in enterocyte apoptosis in MTX+n-3 PUFA rats was accompanied by decreased TNF-α, FAS, FasL, FADD and BID mRNA levels. Decreased NF-κB, COX-2 and TNF-α levels in mucosa was accompanied by a decreased number of IELs and macrophages. Conclusions: n-3 PUFAs inhibit NF-κB/COX-2 induced production of pro-inflammatory cytokines and inhibit cell apoptosis mainly by extrinsic pathway in rats with MTX-induced intestinal damage.     

Comparative study on the inhibitory effects of antioxidant vitamins and radon on carbon tetrachloride-induced hepatopathy

We have previously reported that radon inhalation activates anti-oxidative functions and inhibits carbon tetrachloride (CCl₄)-induced hepatopathy. It has also been reported that antioxidant vitamins can inhibit CCl₄-induced hepatopathy. In the current study, we examined the comparative efficacy of treatment with radon, ascorbic acid and α-tocopherol on CCl₄-induced hepatopathy. Mice were subjected to intraperitoneal injection of CCl₄ after inhaling approximately 1000 or 2000 Bq/m³ radon for 24 h, or immediately after intraperitoneal injection of ascorbic acid (100, 300, or 500 mg/kg bodyweight) or α-tocopherol (100, 300, or 500 mg/kg bodyweight). We estimated the inhibitory effects on CCl₄-induced hepatopathy based on hepatic function-associated parameters, oxidative damage-associated parameters and histological changes. The results revealed that the therapeutic effects of radon inhalation were almost equivalent to treatment with ascorbic acid at a dose of 500 mg/kg or α-tocopherol at a dose of 300 mg/kg. The activities of superoxide dismutase, catalase, and glutathione peroxidase in the liver were significantly higher in mice exposed to radon than in mice treated with CCl₄ alone. These findings suggest that radon inhalation has an anti-oxidative effect against CCl₄-induced hepatopathy similar to the anti-oxidative effects of ascorbic acid or α-tocopherol due to the induction of anti-oxidative functions.     

Effects of Oils Rich in Linoleic and α-Linolenic Acids on Fatty Acid Profile and Gene Expression in Goat Meat

Alteration of the lipid content and fatty acid (FA) composition of foods can result in a healthier product. The aim of this study was to determine the effect of flaxseed oil or sunflower oil in the goat diet on fatty acid composition of muscle and expression of lipogenic genes in the semitendinosus (ST) muscle. Twenty-one entire male Boer kid goats were fed diets containing different levels of linoleic acid (LA) and α-linolenic acid (LNA) for 100 days. Inclusion of flaxseed oil increased (p < 0.05) the α-linolenic acid (C18:3n-3) concentration in the ST muscle. The diet high in α-linolenic acid (p < 0.05) decreased the arachidonic acid (C20:4n-6) and conjugated linolenic acid (CLA) c-9 t-11 content in the ST muscle. There was a significant (p < 0.05) upregulation of PPARα and PPARγ gene expression and downregulation of stearoyl-CoA desaturase (SCD) gene in the ST muscle for the high α-linolenic acid group compared with the low α-linolenic acid group. The results of the present study show that flaxseed oil as a source of α-linolenic acid can be incorporated into the diets of goats to enrich goat meat with n-3 fatty acids, upregulate the PPARα and PPARγ, and downregulate the SCD gene expression.