Mostafa I. Waly

Nitrous oxide decreases cortical methionine synthase transiently but produces lasting memory impairment in aged rats

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.

Increased markers of oxidative stress in autistic children of the Sultanate of Oman.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder of early childhood, and an enumeration about its etiology and consequences is still limited. Oxidative stress-induced mechanisms are believed to be the major cause for ASD. In this study 19 autistic and 19 age-matched normal Omani children were recruited to analyze their degree of redox status and a prewritten consent was obtained. Blood was withdrawn from subjects in heparin-coated tube, and plasma was separated. Plasma oxidative stress indicators such as nitric oxide (NO), malondialdehyde (MDA), protein carbonyl, and lactate to pyruvate ratio were quantified using commercially available kits. A significant elevation was observed in the levels of NO, MDA, protein carbonyl, and lactate to pyruvate ratio in the plasma of Omani autistic children as compared to their age-matched controls. These oxidative stress markers are strongly associated with major cellular injury and manifest severe mitochondrial dysfunction in autistic pathology. Our results also suggest that oxidative stress might be involved in the pathogenesis of ASD, and these parameters could be considered as diagnostic markers to ensure the prevalence of ASD in Omani children. However, the oxidative stress-induced molecular mechanisms in ASD should be studied in detail.

Folate and vitamin B12 deficiency and hyperhomocysteinemia promote oxidative stress in adult type 2 diabetes

OBJECTIVE The purpose of this study was to examine the status of folate and vitamin B12 (B12) in relation to serum homocysteine (HCY) and oxidative stress indices in patients with type 2 diabetes (T2DM). METHODS This case-control study involved 100 Omani adults (50 patients newly diagnosed with T2DM and 50 age- and gender-matched healthy controls). Several parameters were investigated, including dietary intake and biochemical assessments of folate, B12, HCY, oxidative stress markers (glutathione and total antioxidant status), and antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). RESULTS Low serum levels of folate, B12, and hyperhomocysteinemia were prevalent in patients with T2DM compared with controls. Oxidative stress was evident in patients with T2DM as indicated by low serum levels of glutathione, total antioxidant status, and impaired antioxidant enzymatic activities (superoxide dismutase, glutathione peroxidase, and catalase). CONCLUSION The low intake of folate and B12 is associated with low serum levels of these two nutrients and hyperhomocysteinemia in Omani adults with T2DM.

New model for adenine-induced chronic renal failure in mice, and the effect of gum acacia treatment thereon: Comparison with rats

INTRODUCTION 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. METHODS 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. RESULTS 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 (P<0.001) in adenine-treated mice and rats, and this action was incompletely, but significantly (P<0.05), reversed by GA. Adenine significantly (P<0.001) reduced superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration in renal homogenates from both species, and these reductions were significantly (P<0.05) ameliorated by GA. DISCUSSION 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.

Low folate and vitamin B12 nourishment is common in Omani children with newly diagnosed autism

OBJECTIVE Arab populations lack data related to nutritional assessment in children with autism spectrum disorders (ASDs), especially micronutrient deficiencies such as folate and vitamin B12. METHODS To assess the dietary and serum folate and vitamin B12 statuses, a hospital-based case-control study was conducted in 80 Omani children (40 children with ASDs versus 40 controls). RESULTS The ASD cases showed significantly lower levels of folate, vitamin B12, and related parameters in dietary intake and serum levels. CONCLUSION These data showed that Omani children with ASDs exhibit significant deficiencies in folate and vitamin B12 and call for increasing efforts to ensure sufficient intakes of essential nutrients by children with ASDs to minimize or reverse any ongoing impact of nutrient deficiencies.

Pomegranate (Punica granatum) Peel Extract Efficacy as a Dietary Antioxidant against Azoxymethane-Induced Colon Cancer in Rat

Functional foods include antioxidant nutrients which may protect against many human chronic diseases by combating reactive oxygen species (ROS) generation. The purpose of the present study was to investigate the protective effect of pomegranate peel extract (PPE) on azoxymethane (AOM)-induced colon tumors in rats as an in vivo experimental model. Forty Sprague-Dawley rats (4 weeks old) were randomly divided into 4 groups containing 10 rats per group, and were treated with either AOM, PPE, or PPE plus AOM or injected with 0.9% physiological saline solution as a control. At 8 weeks of age, the rats in the AOM and PPE plus AOM groups were injected with 15 mg AOM/kg body weight, once a week for two weeks. After the last AOM injection, the rats were continuously fed ad-libitum their specific diets for another 6 weeks. At the end of the experiment (i.e. at the age of 4 months), all rats were killed and the colon tissues were examined microscopically for lesions suspected of being preneoplastic lesions or tumors as well as for biochemical measurement of oxidative stress indices. The results revealed a lower incidence of aberrant crypt foci in the PPE plus AOM administered group as compared to the AOM group. In addition, PPE blocked the AOM-induced impairment of biochemical indicators of oxidative stress in the examined colonic tissue homogenates. The results suggest that PPE can partially inhibit the development of colonic premalignant lesions in an AOM-induced colorectal carcinogenesis model, by abrogating oxidative stress and improving the redox status of colonic cells.

Lifestyle Habits : Diet, physical activity and sleep duration among Omani adolescents

OBJECTIVES This study aimed to investigate the lifestyle habits-physical activity (PA), eating habits (EH), and sleep duration (SD)-of Omani adolescents, and to examine gender differences in such variables. METHODS 802 Omani adolescents (442 females and 360 males), aged 15-18 years were randomly recruited. Anthropometric indices, PA level, and EH and SD were evaluated by the Arab Teenage Lifestyle questionnaire. A semi-quantitative food frequency questionnaire for dietary assessment was also administered. RESULTS The results showed that although the study subjects had a sedentary lifestyle (lack of PA, average of 6.7 hours sleep, and consumption of high calorie foods), they maintained a normal body mass (less than 25 Kg/m(2)). Males were more than twice as active as females. With respect to EH, there were few gender differences, except in dairy and meat consumption where 62.5% and 55.5% of males consumed more than 3 servings, respectively, compared to 18.78 % and 35.2% of females, respectively. In addition, waist/height ratio, height, reasons for being active, energy drinks, potato consumption, eating sweets, vigorous PA and breakfast EHs were statistically significant independent predictors for BMI, P <0.05 for both males and females. CONCLUSION This study revealed a high prevalence of sedentary behaviors and a low level of physical activity, especially among females. Unhealthy dietary habits were also widely found among both genders. There is an urgent need for more research as well as a national policy promoting active living and healthy eating and discouraging sedentary behaviour among Omani adolescents.

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.

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. Copyright

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.