Intoxicación suicida por nitrito sódico: una peligrosa modalidad en Internet. A propósito de un caso / Suicidal poisoning by sodium nitrite: A dangerous mode from Internet. In regard of a case

Se reporta un caso de suicidio por ingesta de nitritos. Se trata de una joven que fue hallada muerta en un vehículo junto a una serie de objetos, entre ellos una bolsa de polvo blanco etiquetada como «nitrito sódico» y comprimidos de lorazepam, paracetamol y metoclopramida. La autopsia reveló signos compatibles con metahemoglobinemia. Se remitieron muestras de sangre, humor vítreo y contenido gástrico, así como la bolsa con el polvo, los comprimidos y otros objetos al Servicio de Drogas del Departamento de Madrid del Instituto Nacional de Toxicología y Ciencias Forenses. El polvo fue identificado como nitrito sódico, y se detectaron concentraciones de nitritos en las muestras biológicas similares a las de otras intoxicaciones letales. El porcentaje de metahemoglobina en sangre fue del 80%. La existencia de páginas en Internet donde el suicidio con nitritos y metoclopramida es detalladamente descrito, así como el aumento del reporte de este tipo de suicidios, alertan acerca de una posible tendencia. (AU)

A case of suicide by nitrites ingestion is reported: a young woman was found death into a car with various objetcs around her, such as a white powder bag labelled as «sodium nitrite» and pills of lorazepam, acetaminophen and metoclopramide. The autopsy revealed signs compatible with methemoglobinemia and samples of blood, vitreous and gastric content were submitted to the Drugs Service of the National Institute of Toxicology and Forensic Sciences in Madrid, as well as the powder bag, the pills and other objects. The white powder was identified as sodium nitrite, and nitrites concentrations similar to other fatalities were detected in biological samples. The methemoglobin level was 80%. The existence of websites where suicide with nitrites and metoclopramide is described step-by-step, joined to the increasement of reports about these fatalities, alert us to a possible trend. (AU)

Root extracts of Saussurea costus as prospective detoxifying food additive against sodium nitrite toxicity in male rats.

The goal of this study was to investigate the effects of three different extracts of Saussurea costus roots (ethanol, methanol, and water) as a food additive in alleviating the harmful effect of sodium nitrite in rat meals. Thirty-five adult male rats were divided into five groups as follows: control, sodium nitrite (NaNO2; 75 mg/kg BW, single oral dose), S. costus 70% ethanol, 70% methanol, and aqueous extracts (300 mg/kg BW), respectively for four weeks followed by a single dose of NaNO2 24h before decapitation. Results showed that the 70% ethanol extract of S. costus has a higher concentration of total phenolic content, total flavonoids, and antioxidant effect than the 70% methanol and water extracts. Rats pretreated with S. costus extracts reduced the harmful effects induced by NaNO2 and improved the hematological parameters, liver, and kidney function biomarkers as well as lipid profile as compared to the NaNO2 group. Furthermore, S. costus improved the histopathological alterations in the liver and kidney induced by NaNO2 and improved meat sensory evaluation. Conclusively, the 70% ethanol extract of S. costus roots is the most effective extract as an antioxidant against the toxicity of sodium nitrite in male rats and might be used safely as a natural additive in the food industry.

Borate Ameliorates Sodium Nitrite-Induced Oxidative Stress Through Regulation of Oxidant/Antioxidant Status: Involvement of the Nrf2/HO-1 and NF-κB Pathways.

The widespread industrial use of nitrite in preservatives, colorants, and manufacturing rubber products and dyes increases the possibilities of organ toxicity. Lithium borate (LB) is known as an antioxidant and an oxidative stress reliever. Therefore, this study is aimed at examining the effect of LB on nitrite-induced hepatorenal dysfunction. Twenty-eight male Swiss mice were divided into four equal groups. Group 1, the control group, received saline. Group 2 received LB orally for 5 consecutive days at a dose of 15 mg/kg bw. Group 3, the nitrite group, received sodium nitrite (NaNO2) on Day 5 (60 mg/kg bw intraperitoneally). Group 4, the protective group (LB + NaNO2 group), received LB for 5 days and then a single dose of NaNO2 intraperitoneally on Day 5, the same as in Groups 2 and 3, respectively. Samples of blood and kidney were taken for serum analysis of hepatorenal biomarkers, levels of antioxidants and cytokines, and the expression of genes associated with oxidative stress and inflammation. NaNO2 intoxication increased markers of liver and kidney functions yet decreased reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities in blood. NaNO2 also increased the expression of tumor necrosis factor (TNF-α), interleukin-1ß and interleukin-6 (IL-1ß and IL-6). Pre-administration of LB protected mice from oxidative stress, lipid peroxidation, and the decrease in antioxidant enzyme activity. Moreover, LB protected mice from cytokine changes, which remained within normal levels. LB ameliorated the changes induced by NaNO2 on the mRNA of nuclear factor erythroid 2-related factor 2 (Nfr2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), transforming growth factor-beta 2 (TGF-ß2), and glutathione-S-transferase (GST) as determined using quantitative real-time PCR (qRT-PCR). These results collectively demonstrate that LB ameliorated NaNO2-induced oxidative stress by controlling the oxidative stress biomarkers and the oxidant/antioxidant state through the involvement of the Nrf2/HO-1 and NF-κB signaling pathways.

Deterring non-target birds from toxic bait sites for wild pigs.

Toxic baiting of wild pigs (Sus scrofa) is a potential new tool for population control and damage reduction in the US. Field trials testing a prototype toxic bait (HOGGONE 2 containing 5% sodium nitrite [SN]), though, revealed that wild pigs spilled small particles of toxic bait outside of bait stations which subsequently created hazards for non-target species that consumed those particles, primarily passerine birds. To deter non-target birds from consuming particles of spilled bait, we tested four deterrents at mock bait sites (i.e., baited with bird seed) in north-central Colorado, USA during April-May 2020. We found a programable, inflatable deterrent device (scare dancer) reduced bird visitation by an average of 96%. Then, we evaluated the deterrent devices at SN-toxic bait sites in north-central Texas, USA during July 2020, where the devices were activated the morning following deployment of SN-toxic bait. Overall, we found 139 dead wild pigs at 10 bait sites following one night of toxic baiting, which represented an average of 91% reduction in wild pigs visiting bait sites. We found that deterrent devices were 100% effective at deterring birds from toxic bait sites. We found two dead non-target mice at bait sites without deterrent devices. We noted that deploying toxic bait in mid-summer rather than late-winter/early-spring reduced hazards to migrating birds because they were not present in our study area during July. We recommend using deterrent devices (i.e., novel, programmable, battery operated, continuous and erratic movement, and snapping sounds) to reduce hazards to non-target birds at SN-toxic bait sites. We further recommend deploying SN-toxic bait during seasons when migrating birds are not as abundant until further research demonstrates minimal risks to migrating birds.

Safety and toxicology assessment of sodium nitrite administered by intramuscular injection.

Intramuscular (IM) injection of nitrite (1-10 mg/kg) confers survival benefit and protects against lung injury after exposure to chlorine gas in preclinical models. Herein, we evaluated safety/toxicity parameters after single, and repeated (once daily for 7 days) IM injection of nitrite in male and female Sprague Dawley rats and Beagle dogs. The repeat dose studies were performed in compliance with the Federal Drug Administration's (FDA) Good Laboratory Practices Code of Federal Regulations (21 CFR Part 58). Parameters evaluated consisted of survival, clinical observations, body weights, clinical pathology, plasma drug levels, methemoglobin and macroscopic and microscopic pathology. In rats and dogs, single doses of ≥100 mg/kg and 60 mg/kg resulted in death and moribundity, while repeated administration of ≤30 or ≤ 10 mg/kg/day, respectively, was well tolerated. Therefore, the maximum tolerated dose following repeated administration in rats and dogs were determined to be 30 mg/kg/day and 10 mg/kg/day, respectively. Effects at doses below the maximum tolerated dose (MTD) were limited to emesis (in dogs only) and methemoglobinemia (in both species) with clinical signs (e.g. blue discoloration of lips) being dose-dependent, transient and reversible. These signs were not considered adverse, therefore the No Observed Adverse Effect Level (NOAEL) for both rats and dogs was 10 mg/kg/day in males (highest dose tested for dogs), and 3 mg/kg/day in females. Toxicokinetic assessment of plasma nitrite showed no difference between male and females, with Cmax occurring between 5 mins and 0.5 h (rats) or 0.25 h (dogs). In summary, IM nitrite was well tolerated in rats and dogs at doses previously shown to confer protection against chlorine gas toxicity.

Effects of adding sodium nitrite and tea polyphenols on the characterizations and cytotoxicity of carbon nanoparticles from fried pork.

Carbon nanoparticles (CNPs) extensively present in thermal-processed foods. Sodium nitrite (NaNO2) and tea polyphenols (TP) are commonly used in meat processing, while the properties and cytotoxicity of CNPs existed in fried pork added NaNO2 and TP remain unknown. The results showed that compared with no addition (NA, 4.008 ± 0.43 nm) in soaked pork, the smaller diameters of CNPs (0.968 ± 0.44 nm) were found in CNPs-NaNO2-20 group (addition 20 mg/kg NaNO2), the larger (155.8 ± 7.30 nm) in CNPs-TP-100 group (addition 100 mg/kg TP). The diameter of CNPs was positively correlated with the added concentration. CNPs decreased the viability of HL-7702 cells. Compared with NA group, cell viability in CNPs-NaNO2-80 group was obviously (p < 0.05) decreased by 3.17%, while the CNPs-TP-200 group was 13.84% higher. CNPs could block cells growth by arresting cells in S-phase and increasing cellular ROS levels. CNPs generated in fired pork added 200 mg/kg TP in soaking showed less cytotoxicity.

Hesperidin prevents the combined toxicity of decabromodiphenyl ether and sodium nitrite in vitro.

Decabromodiphenyl ether (BDE-209) and Sodium nitrite (SN) coexist in the processing meat and fish foods, but there is no research considering them together. The present study aimed to investigate the binary mixture's toxicity of BDE-209 and SN and explore the protective effect of hesperidin (Hsp) on the combined toxicity. Results showed that compared with the impact of BDE-209 or SN alone, the binary mixture had a synergistic toxic effect on impairing the viability of HepG2 cells, accompanied by oxidative stress, Ca2+ accumulation, mitochondrial dysfunction. The increase of γ-H2AX fluorescent foci and micronuclei number also indicated its genotoxicity. Pretreatment of Hsp could significantly alleviate the above damage caused by the binary combination. These findings revealed the toxicological interaction of BDE-209 and SN and highlighted that food containing abundant natural flavonoids, as hesperidin, could reduce this toxicological risk.

Toxicity of sodium nitrite-based vertebrate pesticides for European starlings (Sturnus vulgaris).

In the 21st century, invasive animals rank second only to habitat destruction as the greatest threat to global biodiversity. Socially-acceptable and cost-effective strategies are needed to reduce the negative economic and environmental impacts of invasive animals. We investigated the potential for sodium nitrite (SN; CAS 7632-00-0) to serve as an avian toxicant for European starlings (Sturnus vulgaris L.). We also assessed the non-target hazard of an experimental formulation of SN that is being developed as a toxicant for invasive wild pigs (Sus scrofa L.). In gavage experiments with European starlings, we identified a lowest observed adverse effect level (LOAEL) for mortality of 2.40% technical SN (w/v; 120 mg SN/kg body mass) and a no observed adverse effect level (NOAEL) for mortality of 1.30% technical SN (65 mg/kg). The exposure of ten starlings to the experimental formulation of SN (10% SN pig toxicant) resulted in one starling mortality during four days of exposure to the toxic bait. Sodium nitrite toxicity presented a moderate hazard to European starlings; thus, the future development of SN as an avian toxicant is dependent upon its cost-effectiveness. We discuss the management of toxic effects and non-target hazards of SN for wild birds, including best practices for toxic baiting of vertebrate pests and management of invasive wild pigs.

BaZiBuShen alleviates altered testicular morphology and spermatogenesis and modulates Sirt6/P53 and Sirt6/NF-κB pathways in aging mice induced by D-galactose and NaNO2.

ETHNOPHARMACOLOGICAL RELEVANCE: Sperm infertility and testicular atrophy are symptoms associated with aging. BaZiBuShen formula (BZBS), a patented Chinese herbal prescription composed of Semen Cuscutae, Fructus Lycii, Epimedii Folium, Fructus Schisandrae Sphenantherae, Fructus Cnidii, Fructus Rosae Laevigatae, Semen Allii Tuberosi., Radix Morindae Officinalis, Herba Cistanches, Fructus Rubi, Radix Rehmanniae Recens, Radix Cyathulae, Radix Ginseng, Cervi Cornu Pantotrichum, Hippocampus, and Fuctus Toosendan, has been used as a kidney-tonifying and anti-aging drug as well as for the treatment of impotence and male infertility in traditional Chinese medicine. AIM OF THE STUDY: We aimed at investigating whether BZBS preserves sperm and testes morphology in aging mice, and to explore the underlying mechanisms. MATERIALS AND METHODS: BZBS was orally administered to aging mice induced by D-galactose (D-gal) and NaNO2 for 65 days. Sperm quality and testes pathophysiological alterations were examined by a Semen Analysis System, hematoxylin-eosin staining, transmission electron microscopy, and mitochondrial complex IV activity. In addition, serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-desoxyguanosine (8-OH-dG), reduced glutathione (GSH), oxidized glutathione disulfide (GSSG), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and tumor necrosis factor-α (TNF-α) were determined by ELISA. The expressions of P450 aromatase (CYP19), sirtuin 6 (Sirt6), P53, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB)-p65, and phospho-NF-κB-p65 (NF-κB-pp65) in the testes were examined by western blot and/or immunohistochemical staining. RESULTS: Sustained exposure to D-gal/NaNO2 caused a deterioration of sperm quality and testes morphology in this rapid aging mouse model. BZBS treatment curtailed these alterations. These beneficial effects were associated with increased serum levels of TAC, GSH/GSSG, T, E2, and FSH, and decreased levels of MDA, TNF-α, and 8-OH-dG. BZBS treatment also downregulated the expressions of P53, iNOS, and NF-κB-pp65, as well as upregulated the expressions of Sirt6 and CYP19 in aging testes. CONCLUSIONS: BZBS preserves testicular morphology and spermatogenesis possibly via inhibition of oxidative stress and the modulation of the Sirt6/P53 and Sirt6/NF-κB signaling pathways. The results shed light on the beneficial effect of BZBS on sperm quality and fertility in aging males.

Mechanism underlying nephroprotective property of curcumin against sodium nitrite-induced nephrotoxicity in male Wistar rat.

The current work examined the outcome of curcumin (20 mg/kg body weight/day) administration on arginase and adenosine deaminase (ADA) activities and other kidney markers, as well as markers of oxidative stress, in Wistar rats exposed to sodium nitrite (NaNO2 ) (60 mg/kg of body weight, single dose) for 28 days. The results revealed that the NaNO2 exposed rats had significantly altered the ADA activities, arginase activities alongside other biomarkers of kidney function, and oxidative stress. However, pretreatment with curcumin significantly mitigated the altered activities ADA and arginase as well as other parameters. This was supported by the histopathological examination of the kidney tissues. Our findings suggest that the alteration in the activities of ADA and arginase could be involved in the mechanism of action employed by NaNO2 and curcumin in the respective induction and prevention of nephrotoxicity. PRACTICAL APPLICATIONS: These results suggest that moderate exposure to the acceptable daily dose of curcumin can improve food-related kidney damage through regulations of ADA and arginase activities, enhancement in the antioxidant system, and suppression of lipid peroxidation.

Glycyrrhizic acid ameliorates sodium nitrite-induced lung and salivary gland toxicity: Impact on oxidative stress, inflammation and fibrosis.

Despite wide application of sodium nitrite (SN) as food additive, it exhibits considerable side effects on various body organs at high dose or chronic exposure. The aim of this study was to test whether Glycyrrhizic acid (GA) could ameliorate SN-induced toxicity in lung and submandibular salivary gland (SMG). A sample size of 30 adult male albino rats was randomly allocated into 3 groups. Group 1 served as control group. Rats were treated orally with 80 mg/kg of SN in group 2 or SN preceded by (15 mg/kg) GA in group 3. Lung & SMG tissues were used for oxidative stress assessment, examination of histopathological changes, fibrosis (MTC, TGF-ß and α-SMA) and inflammation (TNF-α, IL-1ß and CD-68). Concurrent administration of GA ameliorated pulmonary and salivary SN-induced toxicity via restoring the antioxidant defense mechanisms with reduction of MDA levels. GA reduced the key regulators of fibrosis TGF-ß and α-SMA and collagen deposition. In addition to reduction of inflammatory cytokine (TNF-α, IL-1ß) and macrophages recruitments, GA amended both pulmonary and salivary morphological changes. The present study proposed GA as a promising natural herb with antioxidant, anti-inflammatory and antifibrotic effects against pulmonary and salivary SN-induced toxicity.

Chlorella vulgaris ameliorates sodium nitrite-induced hepatotoxicity in rats.

The current was conducted to evaluate the ameliorating effect of Chlorella vulgaris (CV) extract against sodium nitrite-induced hepatotoxicity in rats. Forty-five rats were allocated randomly into 5 groups (n = 9). Group I (GI), control group: orally gavaged with normal saline daily. Group II (GII): orally gavaged with CV extract (70 mg/kg BW) for 3 months. Group III (GIII): orally gavaged with sodium nitrite (80 mg/kg BW) for 3 months. Group IV (GIV): received sodium nitrite as GIII and CV extract as GII simultaneously for 3 months. Group V (GV): received CV extract as GII and then, sodium nitrite as in GIII from the end of first month until the end of the experiment. Sodium nitrite significantly increased the activities of serum alanine aminotransferase, aspartate aminotransferase, and serum concentrations of tumor interleukin 1-ß and necrosis factor α. In addition, it increased concentrations of malondialdehyde and nitric oxide and expression level of caspase-3 in the hepatic tissue. However, it decreased activities of hepatic glutathione peroxidase, catalase, and superoxide dismutase and induced degenerative and necrotic changes in hepatic tissues. In contrast, CV extract administration modulated sodium nitrite-induced inflammation, oxidative stress, and alteration in hepatic tissue function and architecture. This study indicated that CV extract modulated sodium nitrite-induced hepatic toxicity through decreasing oxidative stress and inflammation and enhancing antioxidant enzyme activities in hepatic tissue of rats.

Methanolic extract of Chlorella vulgaris protects against sodium nitrite-induced reproductive toxicity in male rats.

The current study aimed to investigate the protective potential of Chlorella Vulgaris (CV) extract against the reproductive dysfunction induced by sodium nitrite toxicity. Forty-five male Wistar albino rats were assigned into five groups (n = 9). Control group received normal saline orally for 3 months, CV-treated: administered CV extract (70 mg/kg.BW) orally for 3 months, sodium nitrite-treated: received sodium nitrite (80 mg/kg.BW) orally for 3 months, co-treated: simultaneously received CV along with sodium nitrite treatment, orally, daily for 3 months, and CV-pre-treated: pre-treated with CV extract for 4 weeks followed by simultaneous treatment with sodium nitrite and CV extract for additional 8 weeks. Treatment with sodium nitrite significantly decreased serum testosterone and follicle-stimulating hormone concentrations, sperm count, motility, and viability. Besides, it decreased testicular superoxide dismutase and glutathione peroxidase activities while increased malondialdehyde concentration. This effect of sodium nitrite was associated with degenerative, necrotic, vascular, and inflammatory changes in testicular tissues. Treatment of sodium nitrite-intoxicated rats with CV in co-treated and pre-treated groups significantly prevented sodium nitrite-induced alterations of sperm parameters, hormonal concentrations, testicular oxidative-antioxidant status, and histological architecture. This study indicates that CV extract ameliorates the reproductive dysfunction induced by sodium nitrite toxicity via improving reproductive hormonal levels and testicular antioxidant activities.

Glutathione peroxidase 3 in the mud crab Scylla paramamosain: Characterization and regulation under nitrite stress.

Glutathione peroxidases (GPx) are parts of the enzymatic antioxidant system that can eliminate the peroxides produced as effect of reactions of molecules with reactive oxygen species (ROS). In this study, a selenium-dependent glutathione peroxidase 3 cDNAs (designated as SpGPx3) was obtained from the mud crab Scylla paramamosain. The open reading frame (ORF) of SpGPx3 was 639 bp, which encoded a putative protein of 212 amino acids. SpGPx3 protein contained a characteristic GPx signature motif, and an active site motif. Mud crabs were exposed to 20 mg L-1 nitrite for 72 h. Quantitative real-time PCR analysis revealed that the SpGPx3 mRNA was distributed abundantly in mud crab. The transcript levels of antioxidant enzyme genes (SpGPx3, SpSOD and SpCAT) were obviously induced after acute nitrite exposure. After knockdown of the SpGPx3 level, the mortality of mud crabs and malondialdehyde (MDA) content significantly increased under nitrite stress. These results suggested that SpGPx3 played an important role in protecting organisms against oxidative stress.

Effect of acute sodium nitrite intoxication on some essential biometals in mouse spleen.

BACKGROUND AND AIM: Sodium nitrite (NaNO2) is an inorganic salt with numerous applications in a variety of industries, as well as in medicine. Nevertheless, exposure to high levels of NaNO2 is toxic for animals and humans. Sodium nitrite intoxication is shown to decrease the activity of major antioxidant defence enzymes which is dependent on the maintenance of specific ion equilibrium. The aim of the present study was to investigate the effect of acute NaNO2 intoxication on the content of the essential metals iron (Fe), calcium (Ca) and zinc (Zn) in mouse spleen. METHODS: Mature male ICR mice were divided into four groups and subjected to acute NaNO2 exposure by a single intraperitoneal injection of 120 mg/kg body weight. Animals in each group were sacrificed at certain time interval after treatment (1 h, 5 h, 1 day and 2 days). Spleens were excised and processed for atomic absorption spectrometry analysis of Fe, Ca and Zn content. RESULTS: At the first hour after treatment, a decrease in Fe and Ca levels was observed. One day following NaNO2 administration, Zn concentration reached its lowest value and Ca levels remained lower, compared to the untreated controls. In contrast, Fe concentration increased on the first and second day after treatment. CONCLUSION: The results of the present study demonstrate that acute NaNO2 intoxication provokes changes in the endogenous levels of Fe, Ca and Zn in mouse spleen. These findings suggest disruption of the ionic balance and impact on the activity of antioxidant defence enzymes.

Sodium nitrite negatively affects reproductive ability and offspring survival in female mice.

Sodium nitrite (NaNO2) is an industrial chemical that is frequently used as a food additive to prevent botulism and enhance glossiness, such as curing meat. In addition, in some regions, water source NaNO2 concentrations exceed standard regulatory levels. Whether the excessive intake of NaNO2 has toxic effects on female fertility and fetal development remain unknown. In this study, we administered ICR mice control saline, low-dose NaNO2 (60 mg/kg/day), or high-dose NaNO2 (120 mg/kg/day) by intragastric gavage for 21 days. We then assessed oocyte morphology, spindle-chromosome dynamics, mitochondrial distribution, ATP content, apoptotic cell numbers, DNA damage levels, histone modifications, reactive oxygen species (ROS) levels, and offspring survival. Results showed that NaNO2 treatment decreased oocyte number, impaired polar body extrusion, and increased zona pellucida thickness in oocytes. Furthermore, NaNO2 disrupted MII spindle integrity, caused abnormal mitochondrial distribution, decreased ATP content, and increased levels of ROS and H3K4me2. Moreover, the number of oocytes in early stages of apoptosis and with levels of DNA damage increased in NaNO2-treated mice along with decreased offspring numbers and survival rates. We demonstrated the negative effects of NaNO2 on female reproductive abilities in mice.

Protective effect of carnosine and N-acetylcysteine against sodium nitrite-induced oxidative stress and DNA damage in rat intestine.

The widespread use of sodium nitrite (NaNO2) as food preservative, rampant use of nitrogenous fertilizers for agricultural practices, and improper disposal of nitrogenous wastes have drastically increased human exposure to high nitrite levels causing various health disorders and death. In the present study, the protective effect of carnosine and N-acetylcysteine (NAC) against NaNO2-induced intestinal toxicity in rats was investigated. Animals were given a single acute oral dose of NaNO2 at 60 mg/kg body weight with or without prior administration of either carnosine at 100 mg/kg body weight/day for 7 days or NAC at 100 mg/kg body weight/day for 5 days. Rats were killed after 24 h, and intestinal preparations were used for the evaluation of biochemical alterations and histological abrasions. Administration of NaNO2 alone decreased the activities of intestinal brush border membrane and metabolic enzymes and significantly weakened the anti-oxidant defense system. DNA damage was also evident as observed by increased DNA-protein crosslinking and fragmentation. However, prior administration of carnosine or NAC significantly ameliorated NaNO2-induced damage in intestinal cells. Histological studies support these biochemical results, showing intestinal damage in NaNO2-treated animals and reduced tissue injury in the combination groups. The intrinsic anti-oxidant properties of carnosine and NAC must have contributed to the observed mitigation of nitrite-induced metabolic alterations and oxidative damage. Based on further validation from clinical trials, carnosine and NAC can potentially be used as chemo-preventive agents against NaNO2 toxicity.

Potential secondary poisoning risks to non-targets from a sodium nitrite toxic bait for invasive wild pigs.

BACKGROUND: An acute and orally delivered toxic bait containing micro-encapsulated sodium nitrite (MESN), is under development to provide a novel and humane technology to help curtail damage caused by invasive wild pigs (Sus scrofa). We evaluated potential secondary risks for non-target species by: testing whether four different types of micro-encapsulation coatings could reduce vomiting by invasive wild pigs, testing the levels of residual sodium nitrite (SN) in tissues of invasive wild pigs, testing the environmental persistence of SN in vomitus, and conducting a risk assessment for scavengers. RESULTS: Micro-encapsulation coatings did not affect the frequency of vomiting. We identified no risk of secondary poisoning for non-target scavengers that consume muscle, eyes, and livers of invasive wild pig carcasses because residual SN from the toxic bait was not detected in those tissues. The risk of secondary poisoning from consuming vomitus appeared low because ∼90% of the SN was metabolized or broken down prior to vomiting, and continued to degrade after being exposed to the environment. Secondary poisoning could occur for common scavengers that consume approximately ≥15% of their daily dietary requirements of digestive tract tissues or undigested bait from carcasses of invasive wild pigs in a rapid, single-feeding event. The likelihood of this occurring in a natural setting is unknown. The digestive tracts of poisoned invasive wild pigs contained an average of ∼4.35 mg/g of residual SN. CONCLUSION: Data from this study suggest no risks of secondary poisoning for non-target species (including humans) that consume muscle, liver, or eyes of invasive wild pigs poisoned with a MESN toxic bait. More species-specific testing for scavengers that consume digestive tract tissues and undigested bait is needed to reduce uncertainty about these potential risks. © 2017 Society of Chemical Industry.

Carnosine and N-acetyl cysteine protect against sodium nitrite-induced oxidative stress in rat blood.

Sodium nitrite (NaNO2 ) is widely used in the food industry as a preservative and colorant in meat and fish products. Industrialization and improper agricultural practices have greatly increased human exposure to high nitrite levels, mainly through contaminated drinking water, causing various health disorders. We have investigated the protective effect of carnosine (CAR) and N-acetyl cysteine (NAC) on NaNO2 -induced toxicity in rat blood. CAR is a bioactive dipeptide found in mammalian muscle while NAC is a synthetic sulfhydryl amino acid and an important precursor of glutathione. Animals were given a single acute oral dose of NaNO2 at 60 mg/kg body weight with or without prior administration of either CAR or NAC. Rats were sacrificed after 24 h, blood was withdrawn and plasma and erythrocytes were isolated. Administration of NaNO2 alone increased methemoglobin levels and methemoglobin reductase activity, decreased the activities of antioxidant defense and metabolic enzymes and significantly weakened the total antioxidant capacity of rat erythrocytes. Similar effects were seen in plasma of NaNO2 -treated rats. In contrast, administration of CAR or NAC, prior to NaNO2 treatment, markedly attenuated the NaNO2 -elicited deleterious effects. Thus, CAR and NAC can mitigate nitrite-induced metabolic alterations and oxidative damage probably due to their intrinsic biochemical antioxidant properties. This study suggests that CAR and NAC can be potentially used as therapeutic/protective agents against NaNO2 toxicity.

In vivo-like 3-D model for sodium nitrite- and acrylamide-induced hepatotoxicity tests utilizing HepG2 cells entrapped in micro-hollow fibers.

To address the need for a high throughput toxicity test in the modern food industry, an in vivo-like 3-D cell model was constructed in this study to provide an alternative to controversial long-term animal models and to improve the sensitivity and accuracy of the traditional monolayer model. The model formed cell cylindroids within polyvinylidene fluoride (PVDF) hollow fibers and therefore mimicked the microenvironment of liver tissue. Microscopy methods were used, and liver-specific functions were measured to demonstrate the superiority of the model compared to the monolayer model, as well as to optimize the model for best cell performances. Later, toxicity tests of sodium nitrite and acrylamide were conducted in both the 3-D model and the monolayer model to study the sensitivity of the 3-D model in toxicity responses. As expected, HepG2 cells within the 3-D model responded at lower concentrations and shorter exposure times compared to cells within the monolayer model. Furthermore, western blot analysis of apoptosis pathways also supported the argument.