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Traditional salted Thunnus albacares and Scomberoides commersonianus processed with a thyme and other additives recipe were microbiologically and physiochemically characterized to evaluate its safety, quality and storage stability at 23 ± 2°C with a reference to the bacterial floral composition and halophilic bacterial floral types and its potential. This study was conducted in two stages. In the first stage, 15 kg of Thunnus albacares and Scomberoides commersonianus each were bought from local markets and characterized, whereas, in the second stage, 20 kg of Scomberoides commersonianus were stored at 23 ± 2°C for 10 weeks and its storage stability was evaluated. Total aerobic mesophilic bacterial and moderate halophilic bacterial counts were log 2.0 ± 0.78 - 2.4 ± 0.44 CFU/g and log 1.8 ± 0.11 - 2.5 ± 0.53 CFU/g. Enterobacteriaceae, Staphylococcus aureus, mesophilic lactic acid bacteria and yeasts and molds counts were < log 1 CFU/g. Vibrio parahaemolyticus was not detected. Bacillus amyloliquefaciens and B. methylotrophicus were the most dominant halophilic bacteria among the flora. Most of the Bacillus species showed antimicrobial, amino decarboxylation and lipolytic activities. Water activity, peroxide value and acid value were 0.79 ± 0.00 - 0.85 ± 0.00, 2.8 ± 1.4 - 5.6 ± 1.4 meq/kg fat and 2.3 ± 0.62 - 3.2 ± 1.1. Tyramine, histamine, cadaverine and putrescine were found in trace amounts. Salted fish product,s characteristics did not change significantly during storage except NaCl content and colour value a. In conclusion, traditional salted Thunnus albacares and Scomberoides commersonianus were found to be microbiologically safe with good quality and storage stability of 10 weeks.

Background:The use of plant for medicinal purposes has a long history worldwide. There is a lack of research that identifies the antidiabetic effect of edible Omani wild plants. Oxidative stress mediates the pathogenesis of diabetes and it has been suggested that natural antioxidants might be considered as an effective intervention for combating diabetes. Objective: This study aimed to assess the anti-diabetic and antioxidant potential properties of two edible Omani wild plants (Pteropyrum scoparium and Oxalis corniculata) or their mixture in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty-seven male Sprague Dawley rats, weighting 250–300 grams, were allocated into 5 groups: non-diabetic (9 rats/group), diabetic group (7 rats/group), and three diabetic groups that received oral feeding of either Pteropyrum scoparium, Oxalis corniculata, or their mixture (7 rats/group). Diabetes was induced by a single intraperitoneal injection dose of STZ drug, 50 mg/kg body weight. At the end of the experimental trial, after 8 weeks, all rats were fasted overnight and sacrificed; blood glucose was measured, meanwhile pancreatic tissues were dissected and homogenized for the biochemical assessment of oxidative stress markers (glutathione, GSH, and total antioxidant capacity, TAC). Results: STZ resulted in hyperglycemia and oxidative stress (GSH depletion and TAC impairment) in diabetic group as compared to non-diabetic group. Meanwhile the concomitant treatment of diabetic groups with the two wild the edible Omani plants or their mixture have shown a protective effect against the STZ-induced hyperglycemia, but with no effect on oxidative stress. It was noted that for the final boy weight, the improvement was not significant as well. Histopathological examination of the pancreatic tissues showed that the STZ injection lead to pathological changes associated with diabetes in the pancreatic tissues of all diabetic groups. Conclusion: Pteropyrum scoparium and Oxalis corniculata combated the STZ-induced hyperglycemia with no effect on oxidative stress. Also, there was no synergistic effect of Pteropyrum scoparium and Oxalis corniculata on hyperglycemia or oxidative stress.

BACKGROUND AND OBJECTIVE Leaves of basil plant (Ocimum basilicum) are often used for medicinal purposes because of their bioactive constituents, yet the antioxidant properties of this plant are not fully studied in the field of diabetes. The present study investigated the antioxidant property and anti-diabetic effect of two basil cultivars of Ocimum basilicum, 'Italian Genovese' and 'Thyrsiflora', in a Streptozotocin (STZ) rat model of diabetes . MATERIALS AND METHODS Sixty adult Sprague Dawley rats (n = 10/group) were divided into 6 groups: Three non-diabetic and three diabetic groups that either did not receive any supplementation or were supplemented with the leaves extract of one or the other cultivar. After 13 weeks of feeding, all rats were sacrificed, pancreatic tissues were homogenized and used for evaluating oxidative DNA damage and dichlorofluorescein fluorescence (DCF) assay. Blood was collected for the measurements of glucose and insulin. RESULTS The STZ caused oxidative stress in the diabetic group as evidenced by an increase in oxidative DNA damage and also caused DCF production in pancreatic tissues as compared to non-diabetic groups, (p

Casein is an excellent carrier for curcumin, but it is susceptible to hydrolysis in gastrointestinal digestion. This study intended to design a tailored nano-carrier composed of camel casein/bovine whey protein to protect casein and curcumin during digestion. After loading curcumin to the casein, whey protein was added to solution followed by heating at 80°C for 10 min in order to form casein/whey protein aggregations. Binding of curcumin to the solution was assayed by fluorescence. The results showed that in the existence of aggregated whey proteins, stability of curcumin against gastrointestinal condition significantly improved. These results attributed to the protective effect of the aggregated whey proteins during the gastric digestion and denaturation in the accessibility of pepsin to the casein. It was demonstrated that this method might be a good design to combat susceptibility of casein without the use of any synthetic material.

Homocysteine (Hcy) is a sulfur-containing amino acid, which is produced during the metabolism of methionine. Impairment in one carbon metabolism (OCM) is believed to be responsible for elevated plasma homocysteine (Hcy) levels or hyperhomocysteinemia (HHcy), which is considered as an independent risk factor of coronary artery disease (CAD). There are multifactorial causes of HHcy including the genetic factors, polymorphisms of key OCM enzymes, particularly in case of nutritional deficiencies of certain B-vitamins (folate, riboflavin, vitamin B6 and B12), disease state, smoking and drugs. The association between plasma homocysteine levels and cardiovascular disease risk has spawned attention to develop strategies to lower plasma homocysteine levels that may improve the vascular disease-associated morbidity and mortality. The data derived largely from observational and cross-sectional studies as well as from some clinical trials indicate that elevated levels of circulating homocysteine (>12 μM/L) are cytotoxic and can cause vascular damage, increase the risk for developing atherothrombotic CAD, peripheral vascular disease, myocardial infarction, and stroke. Understanding the cellular mechanisms by which homocysteine promotes the oxidative stress-induced vascular dysfunction, has provided sufficient evidence to conduct clinical trials to lower homocysteine levels with B-vitamins as a novel therapeutic approach to patients with cardiovascular diseases. This chapter reviews the scientific evidence about the potential causes of hyperhomocysteinemia and its link as a risk factor in the pathobiology of CAD and the role of B-vitamin supplementation in the prevention of hyperhomocysteinemia-associated CAD.

The significance of elevated blood homocysteine (Hcy) in clinical practice is a serious subject for researchers and is considered as a marker of certain diseases [1]. Hcy, is a sulfur containing, non-proteinogenic amino acid required for the growth of cells and tissues [2, 3]. It is produced exclusively from methionine (Met), an essential amino acid obtained from diet [4]. Hcy is normally present in human plasma at lower concentrations. The normal range is reported to be 5–15 micromol/L [5]. The level could be affected by health-related behaviours, including diet, excessive coffee intake, alcohol consumption, cigarette smoking, and sedentary lifestyle [6, 7]. Total plasma Hcy could be in the form of free Hcy, protein-bound Hcy, oxidized forms of Hcy, and Hcy-thiolactone [3]. This is used as a predictive risk factor for stroke progression, cardiovascular disorders, test for vitamin B12 deficiency, and screening for inborn errors of Met metabolism. An increase of Hcy is referred to as hyperhomocysteinemia (HHcy) which is a sensitive marker of folate and vitamin B 12 deficiency and is associated with an increased risk of cardiovascular disease (CVD), pregnancy complications, cognitive impairment, stoke, and other diseases [8–10]. Plasma levels between 15 and 30 micromol/L are referred as mild HHcy, whereas levels between 31 and 100 micromol/L are moderate HHcy and levels above 100 micromol/L are described as severe HHcy [11]. There are also other studies which report that HHcy are associated with atherosclerosis, thrombosis, birth defects, osteoporosis, diabetes, and renal disease [2]. It is also reported to be highly prevalent in chronic kidney disease (CKD) patients. There are several risk factors that could lead to HHcy- the main cause being insufficient intake of vitamin B group especially folic acid (B9), pyridoxine (B6), or B12 (cyanocobalamin), and several polymorphisms involved in methionine (Met) metabolism [9]. This could also lead to high excretion of Hcy (oxidized Hcy) in urine (homocystinuria) [12]. The relation between HHcy and morphological changes in the organs are extremely important to improve the diagnostic methods and to develop effective treatment.

Inflammation is a natural clinical repair response of body’s immune system to protect its tissues from various noxious stimuli that continues to remodel throughout the lifecycle because of interactions between genes, lifestyles, and environments. There is a link between inflammation, elevated plasma homocysteine levels and cardiometabolic diseases. Multiple mechanisms have been proposed through which homocysteine can modulate the inflammatory response, though the exact mechanism is not clearly understood. The serum homocysteine concentration is considered as an independent risk factor for many disease conditions including cardiovascular diseases (CVD). Epidemiological evidence indicates that moderate consumption of anthocyanins is associated with reduced risk of atherosclerosis and cardiovascular diseases. However, a clear relationship between anthocyanin and homocysteine has not yet been developed. Anthocyanins are water soluble blue, red, and purple pigments, present in the vacuolar sap of the epidermal tissues of plant parts. As therapeutic agents, they are well-accepted in folk medicine worldwide and are linked to a myriad of health benefits. Anthocyanins impart an amazing role in lessening inflammation in body tissues. The molecular mechanisms involved in anti-inflammatory activities include inhibition of pro-inflammatory enzymes, such as cyclooxygenase-2, lipoxygenase and inducible nitric oxide (NO) synthase, inhibition of NF-kB and activating protein-1 (AP-1) and activation of phase II antioxidant detoxifying enzymes, mitogen-activated protein kinase (MAPK), protein kinase C and nuclear factor-erythroid 2-related factor 2. This chapter discusses the interrelationship between hyperhomocysteinemia, inflammation and anthocyanins, as well as the mechanisms of action and anti-inflammatory role of anthocyanins in the prevention of cardiometabolic diseases.

Curcumin has a wide spectrum of biological, pharmaceutical, and antioxidant effects in cancer experimental models. Nitrosamine is commonly used as an experimental oxidizing agent which induces gastric oxidative stress and gastric carcinogenesis in rats. We examined the antioxidant potential effect of curcumin against nitrosamine-induced gastric oxidative stress in rats. Forty Sprague-Dawley rats were randomly divided into 4 groups (10 rats/group). The control group was fed a standard diet and received a single dose of normal saline, the nitrosamine-treated group was fed a standard diet and received an intraperitoneal injection of nitrosamine at a single dose of 100 mg/kg body weight (b.w.). The other two groups received a daily dose of curcumin (200 mg/kg b.w.) via intra-gastric intubation in the presence or absence of nitrosamine injection. After 16 weeks, all rats were sacrificed, and the gastric tissues were dissected for histopathological examination and for biochemical measurements of oxidative stress indices. Our results showed that nitrosamine causes oxidative stress in gastric tissues as evidenced by glutathione depletion, increased level of lipid peroxides, nitric oxide release, impairment of total antioxidant capacity, DNA oxidative damage, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase). Histopathological findings revealed abnormal gastric architecture in association with nitrosamine injection compared to the non-treated control group. Curcumin significantly suppressed the gastric oxidative damage associated with nitrosamine treatment and mitigated its histopathological effect. These results suggest that curcumin, as an antioxidant, has a therapeutic effect against oxidative stress-mediated gastric diseases.

Folate and vitamin B12 deficiency is associated with depletion of the major intracellular antioxidant glutathione, and oxidative stress is emerging as an etiological mechanism for colon cancer. Azoxymethane (AOM), a potent carcinogen, induces colon cancer in rats by causing pathophysiological changes and oxidative stress. We investigated the synergistic effect of folate and vitamin B12 supplementation against AOM-induced carcinogenesis and oxidative stress in rat colon. Adult male rats were distributed into four groups: 1) Basal diet only; 2) AOM injection (15 mg/kg once per week in weeks 5 and 6); 3) Folate and vitamin B12 supplemented diet; 4) Folate and B12 diet with AOM injection. After 16 weeks, rats were sacrificed, colon tissue dissected, indicators of oxidative stress were measured, and immunohistochemical and ultrastructural changes were evaluated. AOM-injected rats showed oxidative stress, evident by glutathione depletion, oxidation of cellular proteins, and DNA oxidative damage. AOM increased mucosal levels of antiapoptotic and proapoptotic proteins Bcl2 and Bax and caused ultrastructure changes in colonic cell organelles. Folate and vitamin B12 supplementation decreased the level of oxidative stress and ameliorated the cytotoxic effects of AOM. In this in vivo experimental model of colon cancer, folate and vitamin B12 supplementation combats carcinogen-induced oxidative stress.

Oxidative stress plays a pivotal role in the development of diabetes and hyperglycaemia. The protective effects of natural extracts against diabetes are mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli (Brassica oleracea) exerts beneficial health effects in several diseases including diabetes; however, the mechanism has not been elucidated yet. The present study was carried out to evaluate the potential hypoglycaemic and antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats. Streptozotocin (STZ) drug was used as a diabetogenic agent in a single intraperitoneal injection dose of 50 mg/kg body weight. The blood glucose level for each rat was measured twice a week. After 8 weeks, all animals were fasted overnight and sacrificed; pancreatic tissues were homogenized and used for measuring oxidative DNA damage, biochemical assessment of glutathione (GSH), and total antioxidant capacity (TAC) as well as histopathological examination for pancreatic tissues was examined. Diabetic rats showed significantly higher levels of DNA damage, GSH depletion, and impaired TAC levels in comparison to non-diabetics (P

D4 dopamine receptor (D4R) activation uniquely promotes methylation of plasma membrane phospholipids, utilizing folate-derived methyl groups provided by methionine synthase (MS). We evaluated the impact of D4R expression on folate-dependent phospholipid methylation (PLM) and MS activity, as well as cellular redox and methylation status, in transfected CHO cells expressing human D4R variants containing 2, 4, or 7 exon III repeats (D4.2R, D4.4R, D4.7R). Dopamine had no effect in non-transfected CHO cells, but increased PLM to a similar extent for both D4.2R- and D4.4R-expressing cells, while the maximal increase was for D4.7R was significantly lower. D4R expression in CHO cells decreased basal MS activity for all receptor subtypes and conferred dopamine-sensitive MS activity, which was greater with a higher number of repeats. Consistent with decreased MS activity, D4R expression decreased basal levels of methylation cycle intermediates methionine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH), as well as cysteine and glutathione (GSH). Conversely, dopamine stimulation increased GSH, SAM, and the SAM/SAH ratio, which was associated with a more than 2-fold increase in global DNA methylation. Our findings illustrate a profound influence of D4R expression and activation on MS activity, coupled with the ability of dopamine to modulate cellular redox and methylation status. These previously unrecognized signaling activities of the D4R provide a unique link between neurotransmission and metabolism.

In this study, the retention of vitamin C in fresh broccoli stored at different temperatures (i.e. chiller, room, cooking, and roasting or baking; 5-120°C) was investigated. The thermal stability of vitamin C in broccoli was analysed at 5, 20, 45, 60, 70, 80, 110, and 120°C. The vitamin C content was measured by the indophenol titration method. Vitamin C was affected negatively at all stored temperatures. The degradation of vitamin C was modelled by first-order reaction kinetics and the reaction rate constants were observed as 9.03×10 -8 and 5.65×10 -3 s -1 when stored at 5°C and 120°C, respectively. The activation energy was estimated as 74.2 kJ/mol within the temperature range used in this study. The lowest decay of vitamin C was observed during the chilling condition. The data on retention of vitamin C in broccoli could be used to determine their stability, when stored as raw, and when heated at different temperatures.

Four types of fibers (i.e. defatted, F1; residue after alkaline digestion, F2; precipitated fibers at pH 5.5, F3; and pH 1.5, F4) were prepared from date-pits. The date-pits were first defatted and then digested by an alkaline solution. The fibers F2 showed the highest amount of cellulose (i.e. 46.0 g/100 g sample), while fibers F3 and F4 showed the lowest amount of cellulose (i.e. F3, 9.3 g/100 g sample). The visual structures of the fibers were determined by Field Emission Scanning Electron Microscope (FESEM). Fibers F1 (i.e. defatted date-pits) showed that lignin was coated over holocellulose, however alkaline digestion clearly showed lignin-coating was removed and fibers (F2) contained two main types of structural matrix (i.e. micro-size trapezoidal particles were embedded in nano-size fine interconnected fibers). Fibers F3 showed highly porous particles, while F4 showed that spherical particles were imbedded in an interconnected fiber matrix. Infrared Fourier Transform (FTIR) peaks within the wave number 500-4000 cm−1 showed different molecular structures of the fibers. X-ray (XRD) patterns showed different crystallinity of the fibers. The crystallinity of the F2 and F4 were 76.7 and 95.5%, respectively and fibers F3 was mainly amorphous in nature.

Background: Sideroxylon mascatense is a wild blueberry plant that traditionally known as “boot” in Oman. Studies on health beneficial effects of this fruit are very limited. Aims and Objectives: This study aimed to evaluate the antioxidant and antitumor properties of Sideroxylon mascatense under different drying methods. Materials and Methods: Freeze (−20°C) and air drying (60 and 90°C) methods were used. The antioxidant potential properties were evaluated using DPPH and ABTS assay. Moreover, the antitumor activities of blueberry extracts were determined using Alamar blue assay. Results: The results of this study revealed that a blueberry extract at 20 mg powder/mL provided the maximum amount of vitamin C, reaching a value of 19.45 mg/100 g dry-basis in the flesh dried at 60°C and 14.24 mg/100 g dry-basis in seed dried at 90°C. The freeze-dried blueberry exhibited the highest percentage of free radical scavenging activity (DPPH) from both fruit flesh (50.8%) and seeds (39.4%) at a concentration of 20 mg/mL indicating a higher antioxidant activity. There was no significant difference in the ability of blueberry extracts to scavenge radical cations (ABTS+) at various concentrations of extracts. However, there was a 40% reduction of ABTS+ radical formation in blueberry flesh extracts obtained from freeze-dried berry at a concentration of 20 mg/mL. On the other hand, blueberry seeds showed variation in the scavenging activity of the ABTS+ radical of 38% after different processing methods. Breast MCF7 and ovarian Ov2008 tumor cell lines were the most sensitive to the dried blueberry. The 50% growth inhibition (IC50) of the freeze-dried blueberry extract at both cell lines was 64 and 69 μg/mL, respectively. Conclusion: Our findings indicated a potent antioxidant activity of Sideroxylon mascatense, but further research is required to isolate the active compounds in the fruit and test their effects in an experimental animal model.

This study aimed to assess the status of B-vitamins (folate, vitamin B6, and B12) and homocysteine (HCY) in the sera of Omani coronary artery disease (CAD) patients. Sixteen Omani patients (10 males and 6 females) gave consent for blood sampling and were enrolled in the study on voluntary basis. All patients were evaluated for their anthropometric and biochemical measurements of B-vitamins, glutathione (reduced and oxidized), HCY, and quantification of N-homocysteinylated albumin protein. It was observed that both male and female patients had a comparable age (57.64 ±9.86, 56.5 ±10.04 years, respectively) with no significant difference, P = 0.69 and both genders were obese based on their body mass index (31.22 ± 8.17 kg/m2 for males and 30.26 ± 4.70 kg/m2for females). Serum levels of folate, vitamins B6, and B12 were lower than the normal reference values in all the study participants. There was depletion in glutathione levels (higher level of oxidized glutathione versus lower level of reduced glutathione) in the sera of all study participants. High serum HCY levels in both males and females (75.81±9.21 and 68.66±8.1 μmol/L, respectively) suggest that both males and females had hyperhomocysteinemia. Correlation coefficient analysis revealed that the serum HCY levels were negatively correlated with serum reduced glutathione, folic acid, vitamins B6, and B12 levels in both male and female study participants. The serum HCY level was positively correlated with age, body mass index, and serum oxidized glutathione. Proteomic measurements of N-homocysteinylation in serum albumin revealed that N-homocysteinylated albumin was present in all the assayed serum samples of study participants. The results suggest that low serum status of B-vitamins might act as a metabolic trigger for the observed hyperhomocysteinemia, oxidative stress, and pathological formation of N-homocysteinylated albumin protein, which collectively aggravates the CAD risk in the studied Omani patients.

Vitamin or mineral supplementation is considered to be the most commonly used medical treatment for autism spectrum disorder (ASD), in addition to other interventions such as neurological and psychological interventions. There is not much evidence of therapeutic efficacy between vitamin and mineral supplementation and improvements in ASD. However, several researchers have noted that patients with ASD have various metabolic and nutritional abnormalities including issues with sulfation, methylation, glutathione redox imbalances, oxidative stress, and mitochondrial dysfunction. There is some evidence that vitamin and mineral supplementation may support these basic physiologic processes. Recently, the nutritional status of ASD patients has been gaining focus in this particular area. Pointing out the nutritional status as a potential etiological factor for attention/communication disorders, more importance has been given to this particular point. Moreover, autistic specific considerations like the feature and behavior of ASD might be increased or at least fall in the higher risk due to the sub-optimal nutritional status.

Maha AH Sulaiman,1 Yahya M Al-Farsi,1 Maha M Al-Khaduri,2 Jumana Saleh,3 Mostafa I Waly4,5 1Department of Family Medicine and Public Health, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khoudh, Sultanate of Oman; 2Department of Obstetrics and Gynecology, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khoudh, Sultanate of Oman; 3Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khoudh, Sultanate of Oman; 4Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University, Al-Khoudh, Sultanate of Oman; 5Nutrition Department, High Institute of Public Health, Alexandria, Egypt Purpose: Literature emerging from Western countries has reported increased levels of serum oxidative stress markers among polycystic ovarian syndrome (PCOS) women. In the Arab region, there is limited research about the association between oxidative stress and PCOS. This study aimed to compare sociodemographic and clinical characteristics, sex hormones, and oxidative stress indices between PCOS women and non-PCOS women and to investigate the correlation between oxidative stress biomarkers and sex hormones.Methods: This hospital-based case-control study was conducted among reproductive-aged women. The study included 51 women diagnosed with PCOS (as per Rotterdam 2003 criteria) and 45 control women who were not diagnosed with PCOS. Serum samples were collected to measure the mean levels of the following sex hormones: total testosterone, dehydroepiandrosterone sulfate, estradiol and progesterone, as well as to measure biomarkers of oxidative stress including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione (GSH), and total antioxidant capacity (TAC).Results: PCOS women exhibited clinical characteristics including irregular menses, hirsutism, and acne compared to the control group (P≤0.05). Significant differences were observed in the waist-hip ratio of PCOS women compared to controls (P=0.004). GPx and GR activity levels appeared to be higher among PCOS women compared to controls; however, no statistically significant differences were observed between the two groups (P>0.05). PCOS women had lower GSH and TAC levels compared to controls with a statistically significant difference observed for GSH levels (P=0.006). Correlation analysis showed a significant negative correlation between estradiol and TAC in the total sample (r=-0.284, P=0.005).Conclusion: This study provides supportive evidence that oxidative stress might play a role in the pathogenesis of PCOS and, hence, oxidative stress parameters could be suggested as diagnostic markers for early diagnosis of high-risk groups. Also, the study provides supportive evidence that obesity and sex hormones, particularly estradiol, in PCOS may contribute to enhanced oxidative stress. Keywords: PCOS, oxidative stress, Oman, case-control, anthropometric, glutathione

Dysfunction of the serotoninergic and glutamatergic systems is implicated in the pathogenesis of autism spectrum disorder (ASD) together with various neuroinflammatory mediators. As the kynurenine pathway (KP) of tryptophan degradation is activated in neuroinflammatory states, we hypothesized that there may be a link between inflammation in ASD and enhanced KP activation resulting in reduced serotonin synthesis from tryptophan and production of KP metabolites capable of modulating glutamatergic activity. A cross-sectional study of 15 different Omani families with newly diagnosed children with ASD (n = 15) and their age-matched healthy siblings (n = 12) was designed. Immunological profile and the KP metabolic signature were characterized in the study participants. Our data indicated that there were alterations to the KP in ASD. Specifically, increased production of the downstream metabolite, quinolinic acid, which is capable of enhancing glutamatergic neurotransmission was noted. Correlation studies also demonstrated that the presence of inflammation induced KP activation in ASD. Until now, previous studies have failed to establish a link between inflammation, glutamatergic activity, and the KP. Our findings also suggest that increased quinolinic acid may be linked to 16p11.2 mutations leading to abnormal glutamatergic activity associated with ASD pathogenesis and may help rationalize the efficacy of sulforaphane treatment in ASD. Autism Res 2016, 9: 621-631. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Plants and their by-products offer a diverse mixture of chemical constituents like natural antioxidants. Date- pits are rich in phenolic compounds that have antioxidant potential. The main objective of this study was to investigate the protective effect of a date-pit extract (DPE) against AOM-induced colonic carcinogenicity and oxidative stress. Thirty-two weanling male Sprauge-Dawley rats were randomly divided into four groups (eight rats in each group). All rats were fed basic diet and water ad libitum, and randomly distributed per treatment groups as follows: negative controls injected with normal saline once a week for two weeks, a cancer group injected intra-peritoneally with azoxymethane (15mg/kg body weight) for two consecutive weeks, and DPE treated groups receiving the extract via the oral route (1.5ml/day) for the entire experiment in the presence or absence of AOM injection. Results showed that DPE contained phytonutrients that were capable of inhibiting chemically-induced oxidative stress in the rat colonic cells. In those animals that consumed DPE, a protective effect was observed against AOM-induced oxidative stress in rat colonic cells as evident by a significant decrease in MDA and oxidized DCF formation in AOM injected and DPE fed groups. It is concluded that DPE has potential antioxidant and anticarcinogenic properties.

Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP.

Environmental toxins and oxidizing agents are the common causes of oxidative stress in different biological systems. Oxidative stress is a common etiological factor of cancer in different human organs, and the oxidative stress-mediated carcinogenesis includes activation of oncogenic transcription factors, inhibition of antioxidant enzymes (catalase, glutathione-S-transferase, glutathione peroxidase, and superoxide dismutase), and depletion of glutathione, the major cellular antioxidant. Clinical studies continue to support the notion that different beehive products (honey, pollen, propolis, royal jelly, and venom) supplementation combats cancer development based on their antioxidant and health properties.

Humans are increasingly exposed to heavy-metals from food, water, medicine, vaccines, and cosmetics. The toxicity of heavy-metals in humans is briefly summarized, links the possible causal relationships between a high heavy-metals body burden and a number of neurological disorders including Alzheimer’s, Parkinson and Autism disorders. This study aimed to assess the antioxidant properties of Astaxanthin (ASTA) to determine the effect of orally administered ASTA capability of restrict accumulation and toxicity of heavy-metals in brain of rats. It also, assess against Hydrogen peroxide induced oxidative stress and antioxidant potential properties of ASTA with comparing the affectivity of 5% and 10% of ASTA in increased glutathione-recycling enzymes (GPx oxidation). A significant change was observed as increased glutathione-recycling enzymes (GPx oxidation) of rats and showed a protective effect against accumulation of Aluminum(AL) in rat’s brain tissues. The results of this in-vivo study demonstrated that ASTA 10% is more can affective in restriction of accumulation and toxicity of Al in rate brain and its contented can protects against oxidative-stress.

Moisture, protein, oil and carbohydrate contents of date–pits varied from 3.1–12.5, 2.3–6.9, 5.0–12.5 and 70.9–86.9 g/100 g date–pits, respectively. BET–monolayer (i.e. strongly bound) moisture content, solids–melting peak (at moisture: 6.7 g/100 g date–pits), and melting point of oil were 4.3 g/100 g dry–solids, 106oC, and 1.8oC, respectively. The major fatty acids were lauric, myristic, palmitic, stearic, oleic, and linoleic acids and polyphenol content varied from 21.0–62.0 mg/g date–pits depending on the varieties, types of solvent and temperature used for extraction. Date–pits showed effectives in animal and poultry feeds and it could be used as value added products, such as: dietary fibres, functional polysaccharides, caffeine–free drinks (similar to coffee), oil (biofuel or cooking oil), and other functional or medicinal products. Date–pits powder and activated carbon from date– –pits showed effective in purifying water by removing different types of pollutants, such as heavy metals, boron, dyes, phenolic compounds, and pesticides. Date–pits also showed effective to be used as ingredient for composed, biomass, and fermentation processes.

Genetic, nutrition, and environmental factors have each been implicated as sources of risk for autism. Oxidative stress, including low plasma levels of the antioxidant glutathione, has been reported by numerous autism studies, which can disrupt methylation-dependent epigenetic regulation of gene expression with neurodevelopmental consequences. We investigated the status of redox and methylation metabolites, as well as the level of protein homocysteinylation and hair mercury levels, in autistic and neurotypical control Omani children, who were previously shown to exhibit significant nutritional deficiencies in serum folate and vitamin B12. The serum level of glutathione in autistic subjects was significantly below control levels, while levels of homocysteine and S-adenosylhomocysteine were elevated, indicative of oxidative stress and decreased methionine synthase activity. Autistic males had lower glutathione and higher homocysteine levels than females, while homocysteinylation of serum proteins was increased in autistic males but not females. Mercury levels were markedly elevated in the hair of autistic subjects vs. control subjects, consistent with the importance of glutathione for its elimination. Thus, autism in Oman is associated with decreased antioxidant resources and decreased methylation capacity, in conjunction with elevated hair levels of mercury.

Particulate air pollution with particle diameters less than 2.5 μm contribute to respiratory and extra-respiratory morbidity and mortality. We have recently reported the first in vivo experimental evidence that Diesel exhaust particles (DEP) in the lung aggravated the renal, pulmonary, and systemic effects of cisplatin (CP)-induced acute renal failure in rats. This in vitro study sought to determine whether and to what extent does DEP exposure exacerbate the effects of CP-induced oxidative stress in human embryonic kidney (HEK-293) cells, and to examine if these effects could be mitigated/prevented with curcumin (the yellow pigment isolated from turmeric). Cells viability, cysteine uptake and oxidative stress indices [glutathione (GSH), total antioxidant capacity (TAC), and the activities of antioxidant enzymes (catalase; glutathione peroxidase; superoxide dismutase)] were evaluated in all study groups. DEP aggravated the CP- induced HEK-293 cells toxicity, as evidenced by decreasing cell viability and by inducing oxidative stress (GSH depletion, TAC impairment, and antioxidant enzymes inhibition). DEP, but not CP, significantly reduced cysteine uptake. Curcumin prevented the observed DEP and CP-induced cellular insults. These findings suggest that DEP augmented the CP-induced toxicity in HEK-293 cells. Curcumin exhibited a strong potential for protection against DEP and CP-induced cytotoxicity.

This study aimed at comparing the effects of feeding mice and rats with adenine to induce a state of chronic renal failure (CRF), and to assess the effect of treatment with gum acacia (GA) thereon.We compared the outcome, in mice, of feeding adenine at three different doses (0.75%, 0.3%, and 0.2%, w/w). Biochemical and histopathological studies were conducted in plasma, urine and renal homogenates from both species.When mice and rats were fed adenine (0.75%, w/w), all treated rats survived the treatment, but all treated mice died within 1-2 days. The dosage in mice was reduced to 0.3%, w/w, for 4 weeks, but again all treated mice died within 3-4 days. A further reduction in the dosage in mice to 0.2%, w/w, for 4 weeks resulted in no mortality, and produced alterations similar to those observed in rats fed adenine at a dose of 0.75%,w/w, for 4 weeks. Plasma creatinine, urea and urinary protein were significantly increased (P0.001) in adenine-treated mice and rats, and this action was incompletely, but significantly (P0.05), reversed by GA. Adenine significantly (P0.001) reduced superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration in renal homogenates from both species, and these reductions were significantly (P0.05) ameliorated by GA.Our data suggest that mice are more sensitive to adenine than rats, and that a dose of adenine of 0.2%, w/w, for 4 weeks in mice is suggested as a model for CRF. In both models, GA (15%, w/v, in the drinking water for 4 weeks) given concomitantly with adenine ameliorated the severity of CRF to a similar extent.

Zizyphus spina-christi (ZSC) fruit is a rich source of bioactive compounds but any medicinal properties in chemoprevention of colon cancer have hitherto not been studied. The aim of the present study was to examine in vivo protective effects of ZSC water extract on colon carcinogenesis in azoxymethane (AOM)-treated rats. Our results showed that ZSC significantly reduced AOM-induced colonic aberrant crypt foci development and AOM-induced oxidative stress as indicated by restoration of endogenous glutathione depletion and abrogating the impairment of total antioxidant capacity. Caspase-3 cleavage, which has been considered as an apoptotic index, was almost undetectable in AOM-treated rats and ZSC exhibited pro-apoptotic effects evidenced by increased levels of cleaved caspase-3. In the studied model, our findings provide the first in vivo evidence that ZSC extract could inhibit the early stage of colon carcinogenesis by preventing oxidative stress and inducing apoptosis.

Synthesis An allopurinol locked nucleic acid (LNA) monomer was prepared by a novel strategy through C6 deamination of the corresponding 8-aza-7-bromo-7- deazaadenine LNA monomer with aqueous sodium hydroxide. An 8-aza-7-deazaadenine LNA monomer was also synthesized by a modification of the new synthetic pathway. N-Glycosylation at the 8-position was prevented by steric hindrance from the 7-bromo atom in the starting material 8-aza-7-bromo-7-deazaadenine. In the final step of the synthesis, the bromine was removed together with a benzyl protecting group by catalytic reduction with ammonium formate to give the required LNA monomers.

Accumulating evidence suggests that oxidative stress induced mechanisms are believed to be associated with the pathophysiology of autism. In this study, we recruited 19 Omani autistic children with age-matched controls to analyze their plasma and serum redox status and the levels of ATP, NAD+ and NADH using well established spectrophotometric assays. A significant decrease was observed in the levels of plasma total antioxidants (TA), reduced glutathione (GSH), superoxide and catalase activity in Omani autistic children as compared to their age-matched controls. In contrary, the level of plasma glutathione peroxidase (GSH-Px) was significantly increased in autistic children. Reduced serum NAD+ and ATP levels and lower NAD+:NADH ratio were observedin patients with autism compared to controls. Finally, a significant inverse correlation was observed between plasma GSH, SOD, catalase activity, and serum NAD+ and ATP levels, and autism severity using Childhood Autism Rating Scale (CARS) scores. The levels of plasma GSH-Px and serum NADH correlated strongly with autism severity whilst no significant correlation was observed for plasma TA. Our data suggests that increased vulnerability to oxidative stress in autism may occur as a consequence of alterations in antioxidant enzymes leading to mitochondrial dysfunction.

Emodin (a rhubarb anthraquinone) has strong antioxidant and anticancer actions, and recent studies indicated that it reduces cellular oxidative stress induced by various insults and drugs. Cisplatin is an anticancer drug that is associated with nephrotoxicity and induces oxidative stress in cultured human kidney (HEK 293) cells. This study aimed to assess the in-vitro antioxidant properties of the emodin against cisplatin-induced oxidative stress in HEK 293 cells. Our study revealed that emodin acted as a potent free radical scavenger and provided nephroprotection against cisplatin-induced oxidative stress. Emodin as low as 0.5 µm did not decrease cell viability and restored the cisplatin-induced glutathione depletion and total antioxidant capacity in a dose-dependent manner. Emodin augmented the cisplatin-induced inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and superoxide dismutase). These results suggest that emodin has the potential to be used as an adjunct therapeutic agent in patients receiving cisplatin treatment.

Although autism is first and foremost a disorder of the central nervous system, comorbid dysfunction of the gastrointestinal (GI) and immune systems is common, suggesting that all three systems may be affected by common molecular mechanisms. Substantial systemic deficits in the antioxidant glutathione and its precursor, cysteine, have been documented in autism in association with oxidative stress and impaired methylation. DNA and histone methylation provide epigenetic regulation of gene expression during prenatal and postnatal development. Prenatal epigenetic programming (PrEP) can be affected by the maternal metabolic and nutritional environment, whereas postnatal epigenetic programming (PEP) importantly depends upon nutritional support provided through the GI tract. Cysteine absorption from the GI tract is a crucial determinant of antioxidant capacity, and systemic deficits of glutathione and cysteine in autism are likely to reflect impaired cysteine absorption. Excitatory amino acid transporter 3 (EAAT3) provides cysteine uptake for GI epithelial, neuronal, and immune cells, and its activity is decreased during oxidative stress. Based upon these observations, we propose that neurodevelopmental, GI, and immune aspects of autism each reflect manifestations of inadequate antioxidant capacity, secondary to impaired cysteine uptake by the GI tract. Genetic and environmental factors that adversely affect antioxidant capacity can disrupt PrEP and/or PEP, increasing vulnerability to autism.

Nephrotoxicity of the anticancer drug cisplatin (CP) involves the generation of reactive oxygen species in renal cortex, and emodin (a rhubarb anthraquinone) has strong antioxidant and anticancer actions. Therefore, we tested here the possible ameliorative effect of emodin on CP nephrotoxicity in rats. Emodin was given orally (10 mg/kg/day for nine consecutive days), and on day 4, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Five days after CP treatment, rats were killed, and blood and urine samples, and kidneys were collected for the assessment of histopathological renal damage and apoptosis, and for biochemical estimation of creatinine and urea concentrations in plasma and urine, several cytosolic antioxidant enzyme activities in kidneys, and urinalyses. CP significantly increased the concentrations of urea and creatinine, and decreased creatinine clearance. It also significantly reduced cortical glutathione concentration and the activity of superoxide dismutase. CP treatment significantly increased urine volume and N-acetyl-b-D-glucosaminidase activity and significantly decreased osmolarity and protein concentrations. Emodin treatment markedly and significantly mitigated all these effects. Sections from saline- and emodin-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with emodin. The concentration of CP in the cortical tissues was not significantly altered by emodin treatment. The results suggested that emodin had ameliorated CP nephrotoxicity in rats. Pending further pharmacological and toxicological studies emodin may be considered a potentially useful nephroprotective agent.

Recent studies indicated that regular consumption of antioxidant-rich foods reduces cellular oxidative stress and protects against health-related problems. This study aimed to assess the in vitro antioxidant properties of the papaya epicarp extract against hydrogen peroxide (H2O2)-induced oxidative stress in human SH-SY5Y neuronal cells. Our study revealed that papaya epicarp extract acted as a potent free radical scavenger and provided neuroprotection against H2O2-induced oxidative stress. Papaya epicarp extract ameliorated glutathione depletion, restored total antioxidant capacity and augmented the inhibition of antioxidant enzymes (catalase, glutathione peroxidases and superoxide dismutase). In conclusion, papaya epicarp extract can be used as a functional dietary ingredient that might help in reducing the neurological health problems associated with various oxidative stress insults.

Background: Methionine synthase (MS) is a ubiquitous enzyme that requires vitamin B12 (cobalamin) and 5-methyl-tetrahydrofolate for the methylation of homocysteine to methionine. Previous studies have shown that acute or chronic ethanol (ETOH) administration results in the inhibition of MS and depletion of glutathione (GSH), and it has been proposed that GSH is required for the synthesis of methylcobalamin (MeCbl). Methods: We measured GSH levels and investigated the ability of different cobalamin cofactors [cyano- (CNCbl), glutathionyl- (GSCbl), hydroxo- (OHCbl), and MeCbl] to support MS activity in liver and brain cortex from control and ETOH-treated rats. Results: In control animals, MS activity was higher in liver than in cortex for all cobalamins and MeCbl-based activity was higher than for other cofactors. S-adenosylmethionine (SAM) was required for OHCbl, CNCbl, and GSCbl-based activity, but not for MeCbl. Feeding an ETOH-containing diet for four weeks caused a significant decrease in liver MS activity, in a cobalamin-dependent manner (OHCbl ≥ CNCbl > GSCbl > MeCbl). In brain cortex, OHCbl, CNCbl, and GSCbl-based activity was reduced by ETOH treatment, but MeCbl-based activity was unaffected. GSH levels were reduced by ETOH treatment in both liver and cortex homogenates, and addition of GSH restored OHCbl-based MS activity to control levels. Betaine administration had no significant effect on GSH levels or MS activity in either control or ETOH-fed groups. Conclusions: The ETOH-induced decrease in OHCbl-based MS activity is secondary to decreased GSH levels and a decreased ability to synthesize MeCbl. The ability of MeCbl to completely offset ETOH inhibition in brain cortex, but not liver, suggests tissue-specific differences in the GSH-dependent regulation of MS activity.

The folate and cobalamin (Cbl-) dependent enzyme methionine synthase (MS) is highly sensitive to oxidation and its activity affects all methylation reactions. Recent studies have revealed alternative splicing of MS mRNA in human brain and patient-derived fibroblasts. Here we show that MS mRNA in SH-SY5Y human neuroblastoma cells is alternatively spliced, resulting in three primary protein species, thus providing a useful model to examine cofactor dependence of these variant enzymes. MS activity was dependent upon methylcobalamin (MeCbl) or the combination of hydroxocobalamin (OHCbl) and S-adenosylmethionine (SAM). OHCbl-based activity was eliminated by depletion of the antioxidant glutathione (GSH) but could be rescued by provision of either glutathionylcobalamin (GSCbl) or MeCbl. Pretreatment of cells with lead, arsenic, aluminum, mercury, or the ethylmercury-containing preservative thimerosal lowered GSH levels and inhibited MS activity in association with decreased uptake of cysteine, which is rate-limiting for GSH synthesis. Thimerosal treatment decreased cellular levels of GSCbl and MeCbl. These findings indicate that the alternatively spliced form of MS expressed in SH-SY5Y human neuronal cells is sensitive to inhibition by thimerosal and neurotoxic metals, and lower GSH levels contribute to their inhibitory action.

BACKGROUND: Nitrous oxide is a commonly used anesthetic that inhibits the activity of methionine synthase, an enzyme involved in methylation reactions and DNA synthesis and repair. This inhibition triggers vacuole formation and degeneration of neurons in areas of the developing and mature brain that are important for spatial memory, raising the possibility that nitrous oxide might have sustained effects on learning. METHODS: To test this possibility, we randomized 18-month-old Fischer 344 rats (n = 13 per group) to 4 h of 70% nitrous oxide + 30% oxygen or 70% nitrogen + 30% oxygen (control) and assessed memory using a 12-arm radial maze for 14 days beginning 2 days after nitrous oxide inhalation. In separate, identically treated groups of rats, we measured methionine synthase activity in the cortex and liver at the end of nitrous oxide exposure and 2 days later (n = 3 rats per group per time point) using a standard assay. RESULTS: Liver and cortical methionine synthase was inhibited during nitrous oxide inhalation (6% and 23% of control in liver and cortex, respectively; P < 0.01). Liver enzyme activity remained depressed 2 days later, whereas cortical enzyme activity recovered. There was no difference in error rate between control and nitrous oxide treated rats. However, those exposed to nitrous oxide took more time to complete the maze and made fewer correct choices before first error (P < 0.05). CONCLUSIONS: Sedation with 70% nitrous oxide profoundly, but transiently, reduces the activity of cortical methionine synthase but produces lasting impairment in spatial working memory in aged rats.

We are currently witnessing a dramatic change in lifestyle and food choices that is accompanied with an increase in the rate of morbidity and mortality from cardiovascular diseases (CVD). Although studies have reported an association of CVD with hyperhomocysteinemia-mediated oxidative stress, the biochemical basis is not known. This case–control study was aimed to evaluate the nutritional and biochemical status of B-vitamins in relation to hyperhomocysteinemia and oxidative stress in newly diagnosed cardiac patients. The retrospective dietary intake of the study subjects (cases and controls) was estimated using a semi-quantitative food frequency questionnaire, and fasting blood samples were drawn to assess their serum levels of B-vitamins (folate, vitamins B6 and B12), homocysteine (HCY), and oxidative stress indices such as glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrites and nitrates (NN). It was observed that the cases had a lower dietary intake of B-vitamins as compared to their matched control subjects as well as to the corresponding recommended dietary allowances. Biochemical analysis of cases, as compared to controls, indicated depletion of GSH, impairment of TAC, and an elevation in the serum levels of HCY, MDA, and NN. These results suggest that lower status (dietary intake and serum levels) of B-vitamins is involved in the etiology of hyperhomocysteinemia and oxidative stress, the typical risk factors for CVD.

Aluminum (Al) is an environmental toxin that induces oxidative stress in neuronal cells. Mushroom cultivar extract (MCE) acted as a potent antioxidant agent and protects against cellular oxidative stress in human cultured neuronal cells. This study aimed to investigate the neuroprotective effect of MCE against Al-induced neurotoxicity in rat brain. Forty Sprague-Dawley rats were divided into 4 groups (10 rats per group), control group, MCE-fed group, Al-administered group and MCE/Al-treated group. Animals were continuously fed ad-libitum their specific diets for 4 weeks. At the end of the experiment, all rats were sacrificed and the brain tissues were homogenized and examined for biochemical measurements of neurocellular oxidative stress indices [glutathione (GSH), Total Antioxidant Capacity (TAC), antioxidant enzymes and oxidized dichlorofluorescein (DCF)]. Al-administration caused inhibition of antioxidant enzymes and a significant decrease in GSH and TAC levels, meanwhile it positively increased cellular oxidized DCF level, as well as Al concentration in brain tissues. Feeding animals with MCE had completely offset the Al-induced oxidative stress and significantly restrict the Al accumulation in brain tissues of Al-administered rats. The results obtained suggest that MCE acted as a potent dietary antioxidant and protects against Al-mediated neurotoxicity, by abrogating neuronal oxidative stress.

Background:Azoxymethane (AOM) induce colon cancer in experimental animal; in mechanism that is mediated by glutathione (GSH) depletion and impairing total antioxidant capacity (TAC) in colonic cells. Objective: This study investigated the effectiveness of, β-Casein (extracted from camel milk) in the prevention of AOM-induced colon cancer.Method: The experimental animals received AOM intraperitonial injection in the presence or absence of oral supplementation of β-Casein, meanwhile the control group was fed basal diet. After 8 weeks, the rats were sacrificed and the colon tissues were examined for aberrant crypt foci (ACF) enumeration and for biochemical measurements of GSH and TAC. Results: Our data show that AOM-induced GSH depletion that was associated with an impaired TAC in colonic mucosal tissues and the ACF counts were significantly high. The concomitant treatments of AOM-injected rats with β-Casein reduce the AOM-mediated carcinogenesis. Conclusion: β-Casein exhibited anti-carcinogenic effect again...

Chrysin (5, 7- dihydroxyflavone) is a flavonoid with several pharmacological properties that include antioxidant, anti-inflammatory and antiapoptotic activities. in this work, we investigated some effects of three graded oral doses of chrysin (10, 50 and 250 mg/kg) on kidney structure and function in rats with experimental chronic renal disease (CKD) induced by adenine (0.25% w/w in feed for 35 days), which is known to involve inflammation and oxidative stress. Using several indices in plasma, urine and kidney homogenates, adenine was found to impair kidney function as it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and N-Acetyl-beta-D-glucosaminidase activity. Furthermore, it raised plasma concentrations of the uremic toxin indoxyl sulfate, some inflammatory cytokines and urinary albumin concentration. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activities, total antioxidant capacity and reduced glutathione were all adversely affected. Most of these adenine – induced actions were moderately and dose -dependently mitigated by chrysin, especially at the highest dose. Chrysin did not cause any overt adverse effect on the treated rats. The results suggest that different doses of chrysin produce variable salutary effects against adenine-induced CKD in rats, and that, pending further pharmacological and toxicological studies, its usability as a possible ameliorative agent in human CKD should be considered.

In a previous study we demonstrated the ability of dopamine (DA) to stimulate phospholipid methylation (PLM) via a novel mechanism involving the D4 dopamine receptor (D4R) in which single-carbon folates appeared to be the primary source of methyl groups. To further understand the relationship between D4R-mediated PLM and folate metabolism, we examined the effect of several folate pathway interventions on the level of basal and DA-stimulated incorporation of [14C]-labeled formate into phospholipids in cultured SH-SY5Y neuroblastoma cells. These interventions included: (i) Overexpression of methenyltetrahydrofolate synthetase (MTHFS). (ii) Treatment with 5-formylTHF. (iii) Treatment with the MTHFS inhibitor 5-formyltetrahydrohomofolic acid (5-formylTHHF). (iv) Growth in nucleoside-free media. 31P-NMR was also used to follow DA-induced changes in cell phospholipid composition. MTHFS overexpression and 5-formylTHHF treatment, both of which lower 5-methylTHF levels, each reduced basal PLM and its stimulation by DA. In contrast, 5-formylTHF, which increases 5-methylTHF, caused a dose-dependent increase in both basal and DA-stimulated PLM. Growth in nucleoside-free media caused time-dependent changes in PLM, which were due to the absence of purine nucleosides. While basal PLM was maintained at a reduced level, DA-stimulated PLM was initially increased followed by a later decrease. Together, these findings indicate a close functional relationship between single-carbon folate metabolism and DA-stimulated PLM, consistent with a role for 5-methylTHF as the methyl donor for the D4R-mediated process.

Hydrogen peroxide is an oxidative stress agent that is associated with depletion of intracellular glutathione and inhibition of antioxidant enzymes in different cell lines. Consumption of antioxidant-rich foods reduces cellular oxidative stress and its related health problems. This study aimed to assess the antioxidant properties of mushroom, Agaricus bisporous cultivar extract, against hydrogen peroxide induced oxidative stress in cultured human hepatic (HepG2) and neuronal (SH-SY5Y) cells. In this study, hydrogen peroxide caused significant oxidative stress in HepG2 and SH-SY5Y cells as demonstrated by glutathione depletion, impairment of total antioxidant capacity and inhibition of antioxidant enzymes (glutathione peroxidase, catalase and superoxide dismutase). Agaricusbisporous extract ameliorated the observed hydrogen peroxide-induced oxidative cellular insult as indicated by restoring the activity of glutathione and the assayed antioxidant enzymes to control levels. The results suggest that mushroom extract as antioxidant properties and protects against the oxidative stress induced by hydrogen peroxide-in cultured human hepatic and neuronal cells.

Activated charcoal (AC) is a sorbent that has been shown to remove urinary toxins like urea and indoxyl sulfate. Here, the influence of AC on kidney function of rats with experimental chronic renal failure (CRF) is investigated. CRF was induced in rats by feeding adenine (0.75%) for four weeks. As an intervention, AC was added to the feed at concentrations of 10%, 15% or 20%. Adenine treatment impaired kidney function: it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and vanin-1. Furthermore, it raised plasma concentrations of the uremic toxins indoxyl sulfate, phosphate and uric acid. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activity, total antioxidant capacity and reduced glutathione were adversely affected. Most of these changes were significantly ameliorated by dietary administration of AC at a concentration of 20%, while effects induced by lower doses of dietary AC on adenine nephrotoxicity were not statistically significant. The results suggest that charcoal is a useful sorbent agent in dietary adenine-induced CRF in rats and that its usability as a nephroprotective agent in human kidney disease should be studied.

Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Results Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. Conclusions The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

In a previous study, we demonstrated the ability of papaya epicarp extract (PEE) to protect against oxidative stress-induced insult in human SH-SY5Y neuronal cells in a mechanism that appeared to be by means of PEE potent antioxidant properties. To further understand this relationship, we examined the effect of PEE intervention on aluminum (Al)-induced cytotoxicity in SH-SY5Y cells. The results indicated that PEE was effective in protecting against Al-induced cell death in a dose-dependent manner. PEE restored the Al-induced inhibition of folate-dependent methionine synthase activity and the antioxidant enzymes (catalase, glutathione peroxidases and superoxide dismutase). PEE ameliorated the Al-induced impairment of intracellular glutathione and total antioxidant capacity. Together, these findings indicate that PEE supplementation can play a neuroprotective role in ameliorating the changes in redox status of SH-SY5Y cells exposed to Al, a well-known environmental toxin that is involved in the pathogenesis of neurodegenerative diseases and neurodevelopmental disorders.