Neuroprotective Potential of Hydroalcoholic Extract of Centella asiatica Against 3-Nitropropionic Acid-Induced Huntington's Like Symptoms in Adult Zebrafish.

Huntington's disease (HD) is an inherited neurodegenerative disease. 3-Nitropropionic acid (3-NP) causes increased reactive oxygen species production and neuroinflammation. Centella asiatica (CA) is a strong antioxidant. The aim of this study is to investigate the effect of hydroalcoholic extract of C. asiatica (HA-CA) on 3-NP-induced HD in adult zebrafish. Adult zebrafish (∼5-6 months old) weighing 470 to 530 mg was used and treated with 3-NP (5 mg/kg intraperitoneal [i.p.]). The animals received HA-CA (80 and 100 mg/L) daily for up to 28 days in water. Tetrabenazine (3 mg/kg i.p.) was used as a standard drug. We have done an open field test (for locomotor activity), a novel tank diving test (for anxiety), and a light and dark tank test (for memory), followed by biochemical analysis (acetyl-cholinesterase [AchEs], nitrite, lipid peroxidation [LPO], and glutathione [GSH]) and histopathology to further confirm memory dysfunctions. 3-NP-treated zebrafish exhibit reductions in body weight, progressive neuronal damage, cognition, and locomotor activity. The HA-CA group significantly reduced the 3-NP-induced increase in LPO, AchEs, and nitrite levels while decreasing GSH levels. Oral administration of HA-CA (80 or 100 mg/L) significantly reduces 3-NP-induced changes in body weight and behaviors, in addition to neuroinflammation in the brain by lowering tumor necrosis factor-α and interleukin-1ß levels. Moreover, HA-CA significantly decreases the 3-NP-induced neuronal damage in the brain. HA-CA ameliorates neurotoxicity and neurobehavioral deficits in 3-NP-induced HD-like symptoms in adult zebrafish.

Replacement of Nitrite in Meat Products by Natural Bioactive Compounds Results in Reduced Exposure to N-Nitroso Compounds: The PHYTOME Project.

SCOPE: It has been proposed that endogenously form N-nitroso compounds (NOCs) are partly responsible for the link between red meat consumption and colorectal cancer (CRC) risk. As nitrite has been indicated as critical factor in the formation of NOCs, the impact of replacing the additive sodium nitrite (E250) by botanical extracts in the PHYTOME project is evaluated. METHOD AND RESULTS: A human dietary intervention study is conducted in which healthy subjects consume 300 g of meat for 2 weeks, in subsequent order: conventional processed red meat, white meat, and processed red meat with standard or reduced levels of nitrite and added phytochemicals. Consumption of red meat products enriched with phytochemicals leads to a significant reduction in the faecal excretion of NOCs, as compared to traditionally processed red meat products. Gene expression changes identify cell proliferation as main affects molecular mechanism. High nitrate levels in drinking water in combination with processed red meat intake further stimulates NOC formation, an effect that could be mitigated by replacement of E250 by natural plant extracts. CONCLUSION: These findings suggest that addition of natural extracts to conventionally processed red meat products may help to reduce CRC risk, which is mechanistically support by gene expression analyses.

Uncured-Labeled Meat Products Produced Using Plant-Derived Nitrates and Nitrites: Chemistry, Safety, and Regulatory Considerations.

Consumers often malign conventional curing agents while concomitantly accepting the natural forms of the same constituents in numerous food products. This paradox ostensibly exceeds all other food-related controversies to date and likely contributes to the rapid expansion of meat products that utilize natural nitrate derivatives. While there is high demand for these products, a fundamental lack of understanding regarding the safety and chemical implications of curing agents, whether derived from synthetic or natural sources, continues to persist. This manuscript elucidates the variations among curing preparations with particular emphasis pertaining to the associated safety, chemical, and regulatory ramifications encompassing these product categories.

Effect of selenium supplements on the antioxidant activity and nitrite degradation of lactic acid bacteria.

Selenium (Se) is one of the essential trace elements in the human body, and Se-enriched lactic acid bacteria (LAB) can improve the biological utilization value of inorganic Se. The aim of this study was to isolate Se-enriched LAB and study their effects on antioxidant activity and nitrite degradation. The Se-enriched LAB L.P2, which was nitrite-tolerant and could grow in 30 µg/mL sodium selenite (Na2SeO3) medium, was isolated from the traditional fermented Chinese sauerkraut. L.P2 belonged to Lactobacillus plantarum according to the 16S rDNA analysis. The biomass and lactic acid production of L.P2 reached to a maximum (9.52 log CFU/mL and 16.99 mg/mL) when 2.0 µg/mL Na2SeO3 was supplemented in the medium. Additionally, the nitrite degradation rate reached 85.76% when the initial concentration of Na2SeO3 was 2.0 µg/mL. The Se-enriched LAB enhanced the scavenging capacity of hydroxyl radical and superoxide free radical of L.P2 and improved the lipid peroxidation and ion-chelating abilities. Moreover, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in Se 4 group (4.0 µg/mL Na2SeO3 was added) reached 48.49 and 50.35 U/mg, respectively. Thus, Se 4 concentration was significantly higher than that of Se 0 group (with no Se added). In particular, SOD and GSH-Px enzymes correlated with nitrite degradation (P < 0.01). Collectively, our results indicate that Se supplementation can enhance the antioxidant capacity of LAB, contribute to its nitrite degradation, and thus may have potential applications in functional foods.

Safer and healthier reduced nitrites turkey meat sausages using lyophilized Cystoseira barbata seaweed extract.

Background Nitrite salts are still common additives in the meat industry. The present study provides a first approach on the employment of the lyophilized aqueous extract (WE) of the Tunisian seaweed Cystoseira barbata for the quality enhancement of turkey meat sausage. Methods WE was supplemented as a natural antioxidant agent to investigate its effectiveness in delaying lipid oxidation turkey meat sausages containing reduced amounts of sodium nitrites. Results On storage day 5, all concentrations of WE (0.01-0.4 %) reduced the meat lipid oxidation by approximately 36 %, as compared to the negative control containing only 80 mg/kg of meat of sodium nitrites as antioxidant. It was noted that within 15 days of refrigerated storage, a meat system containing 80 mg/kg of meat of sodium nitrites and 0.02 % and 0.04 % of WE had similar Thiobarbituric Acid Reactive Substances (TBARS) levels (19±1.32 and 17±1.12 µmol/kg of meat, respectively), which were comparable to the positive control containing sodium nitrites (150 mg/kg of meat) and 0.045 % vitamin C (18.46±1.27 µmol/kg of meat). In-depth, the metabolomic profiling using gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-quadripole-time-of-flight-mass spectrometry (LC-QTOF-MS) analyses of the Tunisian seaweed C. barbata solvent extracts showed that the main active compounds were phenolic compounds, fatty acids and sterols. Conclusions Overall, the cold medium containing C. barbata lyophilized aqueous extrac, with strong antioxidant activity and antihypertensive properties, may open the way to the development of a natural quality enhancement strategy for new functional and ever healthier reduced nitrites meat sausages based on algae.

Vitamin C intake modify the impact of dietary nitrite on the incidence of type 2 diabetes: A 6-year follow-up in Tehran Lipid and Glucose Study.

BACKGROUND: There is no epidemiological study on the association between dietary nitrate (NO3) and nitrite (NO2) and intakes and the risk of type 2 diabetes (T2D). OBJECTIVE: The aim of this study was therefore to examine the potential effect of dietary NO3 and NO2 on the occurrence of T2D. DESIGN: This longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) on 2139 T2D-free adults, aged 20-70 years, followed for a median of 5.8 y. Dietary intakes of NO3 and NO2 were estimated using a 168-food items validate semi-quantitative food frequency questionnaire, at baseline. Multivariate Hazard Ratios (HR) and 95% confidence intervals (CI), adjusted for diabetes risk score (DRS), and dietary intakes of fat, fiber and vitamin C, were calculated for residual energy-adjusted NO3 and NO2 intakes. Since significant interaction (P = 0.024) was found between NO2 and vitamin C intakes in the multivariable model, stratified analyses were done for < and ≥ median vitamin C intakes. RESULTS: Median (inter quartile range; IQR) daily intake of NO3 and NO2 were 410 mg/d (343-499) and 8.77 mg/d (7.53-10.2). An increased risk of T2D was observed among participants who had higher intake of total and animal-based NO2 in participants who had low vitamin C intake (HR = 2.43, 95% CI = 1.45-4.05, HR = 1.88, 95% CI = 1.12-3.15, respectively). We found no significant association between NO3 in overall, and plant- and animal sources as well, with the risk of T2D. Plant-derived NO2 was also unrelated to incidence of T2D. CONCLUSION: Our findings indicated that higher intakes of total and animal-based NO2 may be an independent dietary risk factor for development of T2D in subjects with lower vitamin C intakes.

Green Alternatives to Nitrates and Nitrites in Meat-based Products-A Review.

Several food additives are added in food for their preservation to maintain the freshness of food (antioxidants) or to slow down or stop the growth of microorganisms (preservative agents). Nitrites and nitrates are used as preservative agents in meat. Nitrites give a smoked taste, a pinkish color in the meat and protect the consumers against the risk of bacterial deterioration. Their addition is however very limited as, in high dose, it can have risks on human health and the environment. Nitrites may also combine with secondary or tertiary amines to form N-nitroso derivatives. Certain N-nitroso compounds have been shown to produce cancers in a wide range of laboratory animals. Thus, alternatives of nitrates and nitrites are the object of numerous research studies. Alternatives, such as the addition of vitamins, fruits, chemicals products, natural products containing nitrite or spices, which have similar properties of nitrites, are in evaluation. In fact, spices are considered to have several organoleptic and anti-microbial properties which would be interesting to study. Several spices and combinations of spices are being progressively evaluated. This review discusses the sources of nitrites and nitrates, their use as additives in food products, their physicochemical properties, their negatives effects and the use of alternatives of nitrites and nitrates in preserving meat products.

Relation between nitrate and nitrite food habits with lung cancer.

Nitrites, a probable human carcinogen, generate reactive nitrogen species that may cause damage to the lung. We evaluated the association between nutritional habits related to nitrite and nitrate intake and risk of lung cancer in Mazandaran, Northern Province of Iran. In this case-control study the two groups were matched for gender and age (+/- 5 years). A semi -quantitative food frequency questionnaire (FFQ) was used to collect dietary data about nutritional habits related to nitrate, nitrite, vitamins E and C intake, from 40 lung cancer cases and 40 control subjects admitted at Mazanaran hospitals. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of lung cancer using logistic regression. Mean score of nutritional habits in case group was significantly lower than that in control group (P less than or equal 0.001). We observed a positive association between animal sources of nitrate and nitrite intake (OR = 2.7, 95% CI: 0.13-0.96) and risk of lung cancer. Decreased risk of lung cancer was also observed with fruit intake (OR = 0.26, 95% CI: 1.3-11). Our results indicate a probable association between nutritional habits related to animal sources of nitrate and nitrite intake and the risk of lung cancer that requires to be confirmed by other studies.

Dietary nitrites and nitrates, nitrosatable drugs, and neural tube defects.

BACKGROUND: Amine-containing (nitrosatable) drugs can react with nitrite to form N-nitroso compounds, some of which are teratogenic. Data are lacking on whether dietary intake of nitrates and nitrites modifies the association between maternal nitrosatable drug exposure and neural tube defects (NTDs) in offspring. METHODS: We examined nitrosatable drug exposure and NTD-affected pregnancies in relation to dietary nitrite and total nitrite intake in a case-control study of Mexican American women. We interviewed 184 women with NTD-affected pregnancies and 225 women with normal live births, including questions on periconceptional drug exposures and dietary intake. For 110 study participants, nitrate was also measured in the usual source of drinking water. RESULTS: Women who reported taking drugs classified as nitrosatable were 2.7 times more likely to have an NTD-affected pregnancy than women without this exposure (95% confidence interval [CI] = 1.4-5.3). The effect of nitrosatable drugs was observed only in women with higher intakes of dietary nitrite and total nitrite (dietary nitrite + 5% dietary nitrate). Women within the highest tertile (greater than 10.5 mg/day) of total nitrite were 7.5 times more likely to have an NTD-affected pregnancy if they took nitrosatable drugs (95% CI = 1.8-45.4). The association between nitrosatable drug exposure and NTDs was also stronger in women whose water nitrate levels were higher. CONCLUSIONS: Findings suggest that effects of nitrosatable drug exposure on risk for neural tube defects in offspring could depend on the amounts of dietary nitrite and total nitrite intake.

A nested case-control study of methemoglobinemia risk factors in children of Transylvania, Romania.

In this nested case-control study, we investigated the risk factors for methemoglobinemia (MHG) in 71 children in the Transylvania region of Romania. This study was unique in that the exposures for cases and controls were calculated as continuous values and were reported in milligrams per kilogram per day of nitrate/nitrite based on careful dietary reconstruction and environmental sampling. This procedure allowed us to compare point estimates of nitrate/nitrite exposure with other continuous, categoric, and ranked risk factors such as the presence or absence of diarrheal disease, reported severity of diarrheal disease, the use of vitamin supplements, the presence, absence, and/or duration of breast-feeding, and whether or not first-generation relatives experienced MHG. Analysis of these factors and exposure levels using both univariate and multivariate whole-model tests was performed to understand the relative significance of risk factors at varying levels of exposure to the development of MHG. Univariate and multifactorial analysis of risk factors for MHG underscored that, for this population, MHG is most strongly associated with nitrate/nitrite exposure through the dietary route (p = 0.0318), via feeding of formula and tea made with water containing high levels of nitrates, and that breast-feeding protects infants younger than 6 months of age (p = 0.0244). Our findings also raise questions about the role of diarrheal disease in the development of MHG, as likelihood ratios (likelihood 4.323, p = 0.0376) and multifactorial analysis indicated a significant role for diarrheal disease for some individuals.

Consumption of nitrate, nitrite, and nitrosodimethylamine and the risk of upper aerodigestive tract cancer.

Evidence from animal studies indicates that various N-nitroso compounds are carcinogenic. We investigated whether consumption of foods and beverages containing nitrosodimethylamine, nitrites, and nitrates affected the risk of laryngeal, esophageal, and oral cancer. In a population-based case-control study in western Washington state, dietary consumption of these substances was measured in 645 cases (169 laryngeal, 125 esophageal, and 351 oral) and 458 controls. After adjustment for tobacco, alcohol, and other known risk factors, there was a 52% reduction in the risk of upper aerodigestive tract cancer for individuals who consumed higher amounts of nitrate (upper tertile) compared with the lowest tertile (P < 0.001 for trend). Nitrate intake was associated with a reduction in cancer risk at all three sites. The reduction in the risk of esophageal cancer with increasing nitrate consumption was more evident in frequent tea drinkers than in other subjects. There was no significant association between nitrite consumption and the risk of laryngeal or oral cancer. However, for individuals with a history of canker sores (an indicator of possible endogenous nitrosation), the risk of esophageal cancer was seven times greater in those with high versus low nitrite intake. Consumption of foods high in nitrosodimethylamine was associated with a 79% increased risk of upper aerodigestive tract cancer (P = 0.037 for trend). Cases consumed smoked fish more frequently than did controls [odds ratio (OR) = 3.03]. Daily intake of beer and of nitrite-containing meats were associated with an increased esophageal cancer risk (OR = 2.48 and 1.82, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

[Influence of nitrates on reproduction in domestic mammals]. / Influence des nitrates sur la reproduction chez les mammifères domestiques.

Nitrates and nitrites ingestion has been linked to adverse effects on reproductive efficiency, on the one hand by abortion in acute or subacute toxicity, on the other hand by impairment of fertility in chronic exposition. However, experimental studies show heterogeneous results and proposed mechanisms are still hypothetic. Experimental studies realised in rabbit in National Veterinary School of Nantes are presented. No detrimental effect on reproduction performances was seen in female rabbits given nitrate in the drinking water at levels of 250 or 500 mg/l during 22 weeks, but a decrease in retinol concentration in the liver of young rabbits born of exposed mother, and drinking themselves water with nitrate during 5 weeks, was observed.

Suspected cyanide poisoning in smoke inhalation: complications of sodium nitrite therapy.

A 78 year old man was found comatose, apneic, and asystolic after closed-space smoke inhalation. He was successfully resuscitated to pulse and blood pressure at the scene. A cyanide component to the poisoning was suspected and two 300 mg doses of sodium nitrite were administered, resulting in significant hypotension. Although high methemoglobin levels were not induced, when added to simultaneously obtained carboxyhemoglobin levels, the total amount of non-oxygen transporting hemoglobin remained nearly constant for about 4-1/2 hours before hyperbaric oxygen (HBO) therapy could be administered. The patient later died in multi-organ system failure. Admission whole blood cyanide level was only 0.34 mcg/mL. These sodium nitrite adverse effects can be avoided by slow intravenous infusion and by administering only recommended doses. In smoke inhalation victims with suspected cyanide poisoning, sodium thiosulfate should be administered first, and sodium nitrite withheld until after the patient is receiving HBO therapy. When available, hydroxocobalamin (which neither induces methemoglobinemia nor causes hypotension) may be the specific cyanide antidote of choice for victims of smoke inhalation.

Food in the aetiology of cancer.

During recent years much evidence has accumulated indicating that diet and nutrition may be important in the aetiology of human cancer. This paper discusses some of the components of diet that have been implicated as both causative and protective agents. Total calorie intake and overnutrition have been associated with breast and uterine cancers, high fat intake with cancer of the breast and large bowel and nitrates with gastric cancer. High fibre intakes are suggested to protect against colo-rectal cancer, and vitamin A, selenium and vitamin E have been inversely associated with various cancers.

Selenium, estradiol 17 beta, nitrites, and human breast cancer.

Breast cancer is the most common cancer in women in the United States. Although there is a large body of studies dealing with selenium, estrogens and nitrites in relation to cancer, most of them are correlated singly and the dynamics of carcinogenesis are overly simplified. The epidemiologic and etiologic effects of selenium, estrogens and nitrites in human breast cancer are traced in their important dimensions. A hypothesis for the interaction of these factors, especially in relation to the erythrocyte is presented within a multi-stage focus of carcinogenesis. A biochemical process for breast cell carcinogenesis in general is postulated and the erythrocyte interaction with breast cancer is diagramed. An enzyme "X" is postulated (estradiase) as a facilitator in vivo of the necessary biochemical conversion of estradiol 17 to a carcinogen.