Hospital Prevalence of Colorectal Cancer among Colonoscopy Recipients Attending a Tertiary Hospital in Oman: A Cross-Sectional Study.

PURPOSE: Evidence from industrialized/developed countries showed that colorectal cancer (CRC) incidence rates have significantly dropped due to the widespread use of colonoscopy. In Arab countries, however, the CRC had been reported to have increased. Despite the concerted effort in the primary prevention and widespread use of colonoscopy, to our knowledge, there have been no reports of the prevalence rate of CRC among colonoscopy recipients from Oman. This study aims to explore the CRC prevalence estimates over selected sociodemographic characteristics among colonoscopy-recipients at a tertiary hospital in Oman over five years of follow-up. The regional variations in Oman were also examined in this study. METHODS: This hospital-based cross-sectional study reviewed reports of colonoscopies performed over 5-years of retrospective follow-up at a tertiary hospital in Oman. CRC prevalence estimates were calculated over age, gender, governorate, and time of follow-up. RESULTS: A total of 442 CRC cases were enumerated among 3701 colonoscopies, with an overall CRC prevalence estimate of 11.9 per 100 colonoscopies (95% CI: 10.9, 13.0). Gender-specific CRC prevalence was higher among males compared with females (13.3 vs. 10.5). Age-specific CRC prevalence increased with advancing age, from 2.8 among those less than 40 years of age to 26.5 among aged 70 years or more. Regional CRC prevalence was highest among residents in Batinah Governorate. Over the 5-years of follow-up, there was a slow rise in CRC prevalence with an annual increment of 0.59%. CONCLUSION: The study provides supportive evidence for a steady increase in CRC prevalence over age categories and years of follow-up and depicted the variations of gender-specific CRC prevalence estimates over increasing age categories. The study calls for timely formulation and adoption of national CRC screening programs centered on the colonoscopy use as primary prevention and maximizing its utilization and efficiency.

Folate/Vitamin B12 Supplementation Combats Oxidative Stress-Associated Carcinogenesis in a Rat Model of Colon Cancer.

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.

Reproductive toxicity to male mice of nose only exposure to water- pipe smoke.

BACKGROUND/AIMS: Water-pipe smoking (WPS) is popular in the Middle East and is starting to gain popularity in several Western countries as well. It is widely and erroneously perceived to be less harmful than other forms of tobacco use. The reproductive adverse effects of cigarette smoking have been studied before with conflicting results, but data on the possible adverse reproductive effects of WPS are lacking. Here, we assessed the effects of nose-only exposure to mainstream WPS generated by commercially available honey-flavored "moasel" tobacco in mice. METHODS: The duration of the session was 30 min/day for one month. Control mice were exposed to air. Twenty-four h after the last exposure, mice were killed and the testes and plasma removed for analysis. In testicular homogenates total protein, alkaline phosphatase activity, several indices of oxidative damage and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) were quantified. The plasma concentrations of leptin, testosterone, estrogen and luteinizing hormone (LH) were also measured. Histological analysis of testes and lungs was also conducted. RESULTS: WPS caused statistically significant decreases in the plasma concentrations of leptin, testosterone, and LH, and in the concentrations of total protein and the antioxidant indices measured. A statistically non-significant decrease in VEGFR2 protein in the WPS--exposed mice compared to the control mice was also found. The body and testicular weights of mice exposed to WPS, as well as their testicular alkaline phosphatase activity and light microscopic histology, and plasma estrogen concentration were all not significantly affected by WPS. CONCLUSION: Further studies on the functional implications of these findings in mice exposed to WPS for longer durations are warranted.

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts.

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.

Effectiveness of Mediterranean Diet on Daytime Sleepiness among Individuals with Type 2 Diabetes Mellitus in Oman.

Background Sleep disturbance is a major complaint among individuals with diabetes mellitus and may be augmented by dietary interventions. The objective of this randomized controlled trial was to determine the effectiveness of a Mediterranean diet intervention on daytime sleepiness among individuals with type 2 diabetes mellitus (T2DM) in Oman. Methods In total, 134 eligible individuals with T2DM (61 and 73 participants in the intervention and control groups, respectively) were recruited. The intervention participants underwent a 6-month Mediterranean diet intervention consisting of individual dietary counseling, cooking classes, phone calls, and social media messages, while the control group continued with standard diabetes care. Daytime sleepiness was assessed using the Epworth Sleepiness Scale. All data was analyzed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY, USA). Results Daytime sleepiness was evident, with ∼ 30% of the participants experiencing it, with no significant difference between control and intervention participants at baseline. There was a significant reduction in daytime sleepiness in both the intervention and control groups after 6 months, with daytime sleepiness significantly lower in the intervention group, with a modest difference of 42.56% ( p < 0.001). Conclusion Adherence to the Mediterranean diet is effective in reducing daytime sleepiness among individuals with T2DM. Clinical Trial UMIN000041152.

Protective effects of emodin against cisplatin-induced oxidative stress in cultured human kidney (HEK 293) cells.

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.

Application of Mediterranean Diet in Cardiovascular Diseases and Type 2 Diabetes Mellitus: Motivations and Challenges.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of disability and death in many countries. Together with CVD, Type 2 diabetes mellitus (T2DM) accounts for more than 80% of all premature non-communicable disease deaths. The protective effect of the Mediterranean diet (MedDiet) on CVD and its risk factors, including T2DM, has been a constant topic of interest. Notwithstanding, despite the large body of evidence, scientists are concerned about the challenges and difficulties of the application of MedDiet. This review aims to explore the motivations and challenges for using MedDiet in patients with CVD and T2DM. DESIGN: An electronic search was conducted for articles about MedDiet published in PubMed, ScienceDirect, Scopus, and Web of Science up to December 2021, particularly on CVD and T2DM patients. From a total of 1536 studies, the final eligible set of 108 studies was selected. Study selection involved three iterations of filtering. RESULTS: Motivation to apply MedDiet was driven by the importance of studying the entire food pattern rather than just one nutrient, the health benefits, and the distinct characteristics of MedDiet. Challenges of the application of MedDiet include lacking universal definition and scoring of MedDiet. Influences of nutritional transition that promote shifting of traditional diets to Westernized diets further complicate the adherence of MedDiet. The challenges also cover the research aspects, including ambiguous and inconsistent findings, the inexistence of positive results, limited evidence, and generalization in previous studies. The review revealed that most of the studies recommended that future studies are needed in terms of health benefits, describing the potential benefits of MedDiet, identifying the barriers, and mainly discussing the effect of MedDiet in different populations. CONCLUSIONS: In general, there is consistent and strong evidence that MedDiet is associated inversely with CVD risk factors and directly with glycemic control. MedDiet is the subject of active and diverse research despite the existing challenges. This review informs the health benefits conferred by this centuries-old dietary pattern and highlights MedDiet could possibly be revolutionary, practical, and non-invasive approach for the prevention and treatment CVD and T2DM.

The Impact of COVID-19 on Physical (In)Activity Behavior in 10 Arab Countries.

Insufficient physical activity is considered a strong risk factor associated with non-communicable diseases. This study aimed to assess the impact of COVID-19 on physical (in)activity behavior in 10 Arab countries before and during the lockdown. A cross-sectional study using a validated online survey was launched originally in 38 different countries. The Eastern Mediterranean regional data related to the 10 Arabic countries that participated in the survey were selected for analysis in this study. A total of 12,433 participants were included in this analysis. The mean age of the participants was 30.3 (SD, 11.7) years. Descriptive and regression analyses were conducted to examine the associations between physical activity levels and the participants' sociodemographic characteristics, watching TV, screen time, and computer usage. Physical activity levels decreased significantly during the lockdown. Participants' country of origin, gender, and education were associated with physical activity before and during the lockdown (p < 0.050). Older age, watching TV, and using computers had a negative effect on physical activity before and during the lockdown (p < 0.050). Strategies to improve physical activity and minimize sedentary behavior should be implemented, as well as to reduce unhealthy levels of inactive time, especially during times of crisis. Further research on the influence of a lack of physical activity on overall health status, as well as on the COVID-19 disease effect is recommended.

Ethanol lowers glutathione in rat liver and brain and inhibits methionine synthase in a cobalamin-dependent manner.

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.

Effect of curcumin on cisplatin- and oxaliplatin-induced oxidative stress in human embryonic kidney (HEK) 293 cells.

Generation of reactive oxygen species (ROS) is involved in the nephrotoxicity of platinum anticancer drugs. This study involved incubation of human embryonic kidney (HEK) 293 cells in cell culture media supplemented with cisplatin or oxaliplatin in the presence or absence of curcumin, a well-studied antioxidant. Thereafter several indices of oxidative stress have been measured, which included glutathione (GSH), total antioxidant capacity (TAC), and antioxidant enzymes [(superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX)]. The impact of platinum drugs on cells viability, lipid peroxidation, and lactate dehydrogenase leakage was also examined. The results show that at both acute (60 min) and chronic (24 h) durations of incubation, cisplatin and oxaliplatin induced oxidative stress as evidenced by significant inhibition of the activities of SOD, CAT, and GPX enzymes as well as significant reduction of the concentrations of GSH and TAC. Curcumin ameliorated the oxidative stress induced by these insults by significantly restoring the measured oxidative indices. Our findings provide evidence that curcumin significantly ameliorates oxidative stress induced by both cisplatin and oxaliplatin in HEK cells.

Methylation-related metabolic effects of D4 dopamine receptor expression and activation.

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.

The Role of Vitamins in Autism Spectrum Disorder: What Do We Know?

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.

Polycystic ovarian syndrome is linked to increased oxidative stress in Omani women.

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.

Association between Dietary and Lifestyle Indices and Colorectal Cancer in Oman: A Case-Control Study

Background: Colorectal cancer (CRC) represents a heterogeneous group of diseases characterized by uncontrolled growth and spread of abnormal cells in the body. CRC vary on the basis of both the biologic features of the disease and its associated lifestyle characteristics. The risk of CRC increases with several modifiable factors including obesity, physical inactivity, a diet high in red or processed meat, heavy alcohol consumption, and possibly inadequate intake of fruits and vegetables. We aimed to establish a baseline data for dietary and lifestyle characteristics of Omani adults diagnosed with CRC. Methods: A Case control study conducted at Sultan Qaboos University Hospital, a referral hospital for CRC patients in Oman, and included 279 subjects (109 diagnosed CRC cases and 170 matched controls). All study subjects were recruited on volunteer basis and personally interviewed for preset questions related to sociodemographic data, anthropometric assessment, dietary intake and physical activity. Results: There was no significant difference between cases and controls regarding smoking, alcohol intake, physical activity and dietary fiber intake. However the enrolled cases were more overweight (OR =3.27. 95% CI: 1.91, 7.27), and, had a higher caloric (p =0.001) and macronutrient intake (carbohydrate: p = 0.001; protein: p = 0.017; saturated fat: P = 0.034) than the controls. In addition, the dietary pattern of the cases was characterized by a trend towards low vegetables and fruits intake. Conclusion: CRC maybe prevented through dietary management of high risk groups. This primary prevention approach will ultimately reduce the burden of CRC in Oman.

Psychological burden among women with polycystic ovarian syndrome in Oman: a case-control study.

PURPOSE: Previous studies in Euro-American populations have shown that women with polycystic ovarian syndrome (PCOS) have increased levels of "psychological burden". While PCOS has been reported in Arab countries such as Oman, there is a dearth of studies of the occurrence of psychological burden among PCOS women in the Arab region. This study aimed to compare sociodemographic and clinical characteristics of PCOS women diagnosed with non-PCOS women and prevalence of severity of depression, anxiety and stress and to explore the association between PCOS and indices of psychological disturbances after adjusting for potential confounding factors. PATIENTS AND METHODS: This hospital-based case-control study was conducted among women aged 16-49 years. The study included 52 women diagnosed with PCOS (as per Rotterdam 2003 criteria) and 60 control who were PCOS-free. The presence of psychological burden - depression, anxiety and stress - was quantified using Depression, Anxiety and Stress Scale-21 (DASS-21). RESULTS: The crude odds ratios (ORs) generated by logistic regression models indicated an increased risk of depression, anxiety and stress among women with PCOS compared to controls. The adjusted OR also indicated an increased risk of depression (OR =1.10; 95% confidence interval [CI] 0.50, 2.43), anxiety (OR =1.09; 95% CI 0.47, 2.52) and stress (OR =1.45; 95% CI 0.68, 3.12), However, no statistical differences were observed along the three psychological distresses (p>0.05) between the two study groups. CONCLUSION: The study indicates that the presence of PCOS is associated with an increased risk of psychological burden. If this study will withstand further scrutiny, meeting psychological needs of such population would need to be contemplated.

Low nourishment of B-vitamins is associated with hyperhomocysteinemia and oxidative stress in newly diagnosed cardiac patients.

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.

Ameliorative Effects of Pomegranate Peel Extract against Dietary-Induced Nonalcoholic Fatty Liver in Rats.

Non-alcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is associated with oxidative stress. In this study, we investigated the potential protective effect of pomegranate (Punica granatum L.) peel extract (PPE) against oxidative stress in the liver of rats with NAFLD. Sprague-Dawley rats were fed a high fat diet (HFD), 20% corn oil, or palm oil for 8 weeks in the presence or absence of PPE. The control group was fed a basal diet. The progression of NAFLD was evaluated histologically and by measuring liver enzymes (alanine transaminase and aspartate transaminase), serum lipids (triglycerides and total cholesterol), and oxidative stress markers. The HFD feeding increased the body weight and caused NAFLD, liver steatosis, hyperlipidemia, oxidative stress, and elevated liver enzymes. Administration of PPE ameliorated the hepatic morphology, reduced body weight, improved liver enzymes, and inhibited lipogenesis. Furthermore, PPE enhanced the cellular redox status in the liver tissue of rats with NAFLD. Our findings suggest that PPE could improve HFD-induced NAFLD via abolishment of hepatic oxidative damage and hyperlipidemia. PPE might be considered as a potential lead material in the treatment of NAFLD and obesity through the modulation of lipid metabolism.

Altered kynurenine pathway metabolism in autism: Implication for immune-induced glutamatergic activity.

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.

Low Nourishment of Vitamin C Induces Glutathione Depletion and Oxidative Stress in Healthy Young Adults.

The present study was conducted to assess the status of vitamin C among healthy young adults in relation to serum antioxidant parameters [glutathione (GSH), thiols, and total antioxidant capacity, (TAC)], and oxidative stress markers [malondialdehyde (MDA), and nitrites plus nitrates (NN)]. A prospective study included 200 young adults, and their dietary intake was assessed by using food diaries. Fasting plasma vitamin C, serum levels of GSH, thiols, TAC, MDA, and NN were measured using biochemical assays. It was observed that 38% of the enrolled subjects, n=76, had an adequate dietary intake of vitamin C (ADI group). Meanwhile, 62%, n=124, had a low dietary intake of vitamin C (LDI group) as compared to the recommended dietary allowances. The fasting plasma level of vitamin C was significantly higher in the ADI group as compared to the LDI group. Oxidative stress in the sera of the LDI group was evidenced by depletion of GSH, low thiols levels, impairment of TAC, an elevation of MDA, and increased NN. In the ADI group, positive correlations were found between plasma vitamin C and serum antioxidant parameters (GSH, thiols, and TAC). Meanwhile, the plasma vitamin C was negatively correlated with serum MDA and NN levels. This study reveals a significant increase of oxidative stress status and reduced antioxidant capacity in sera from healthy young adults with low intake of the dietary antioxidant, vitamin C.

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles.

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.