The effect and mechanism of combined exposure of MC-LR and NaNO2 on liver lipid metabolism.

Microcystin-LR (MC-LR) and sodium nitrite (NaNO2) co-exist in the environment and are hepatotoxic. The liver has the function of lipid metabolism, but the impacts and mechanisms of MC-LR and NaNO2 on liver lipid metabolism are unclear. Therefore, we established a chronic exposure model of Balb/c mice and used LO2 cells for in vitro verification to investigate the effects and mechanisms of liver lipid metabolism caused by MC-LR and NaNO2. The results showed that after 6 months of exposure to MC-LR and NaNO2, the lipid droplets content was increased, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were raised in the liver (P < 0.05). Moreover, MC-LR and NaNO2 synergistically induced hepatic oxidative stress by decreasing total superoxide dismutase (T-SOD) activity and glutathione (GSH) levels and increasing malondialdehyde (MDA) content levels. In addition, the levels of Nrf2, HO-1, NQO1 and P-AMPK was decreased and Keap1 was increased in the Nrf2/HO-1 pathway. The key factors of lipid metabolism, SREBP-1c, FASN and ACC, were up-regulated in the liver. More importantly, there was a combined effect on lipid deposition of MC-LR and NaNO2 co-exposure. In vitro experiments, MC-LR and NaNO2-induced lipid deposition and changes in lipid metabolism-related changes were mitigated after activation of the Nrf2/HO-1 signaling pathway by the Nrf2 activator tertiary butylhydroquinone (TBHQ). Additionally, TBHQ alleviated the rise of reactive oxygen species (ROS) in LO2 cells induced by MC-LR and NaNO2. Overall, our findings indicated that MC-LR and NaNO2 can cause abnormal liver lipid metabolism, and the combined effects were observed after MC-LR and NaNO2 co-exposure. The Nrf2/HO-1 signal pathway may be a potential target for prevention and control of liver toxicity caused by MC-LR and NaNO2.

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)

Effect of bacosides, alcoholic extract of Bacopa monniera Linn. (brahmi), on experimental amnesia in mice.

To investigate the effect of bacosides (alcoholic extract of brahmi) on scopolamine (3 mg kg(-1), ip), sodium nitrite (75 mg kg(-1), ip) and BN52021 (15 mg kg(-1), ip) induced experimental amnesia in mice, using Morris water maze test, all the agents were administered 30 min before the acquisition trials on each day and repeated for 4 consecutive days, and on 5th day during the retrieval trials. Bacosides on anterograde administration (before training) in mice, significantly decreased the escape latency time (ELT) during the acquisition trials for 4 consecutive days and increased the time spent (TS) in target quadrant during the retrieval trials on 5th day, and on retrograde administration (after training) bacosides were found not to affect TS significantly. Bacosides also significantly decreased the ELT and increased the TS in mice treated anterogradely with scopolamine and sodium nitrite. Bacosides did not exhibit any significant effect on TS of mice treated retrogradely with sodium nitrite. On the other hand, bacosides significantly increased the TS of mice treated retrogradely with BN52021. On the basis of the present results it can be concluded that bacosides facilitate anterograde memory and attenuate anterograde experimental amnesia induced by scopolamine and sodium nitrite possibly by improving acetylcholine level and hypoxic conditions, respectively. Beside this bacosides also reversed BN52021 induced retrograde amnesia, probably due to increase in platelet activating factor (PAF) synthesis by enhancing cerebral glutamate level.