Hydrogen Sulfide (H2S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants.

In view of the significant role of H2S in brain functioning, it is proposed that H2S may also possess protective effects against adverse effects of neurotoxicants. Therefore, the objective of the present review is to discuss the neuroprotective effects of H2S against toxicity of a wide spectrum of endogenous and exogenous agents involved in the pathogenesis of neurological diseases as etiological factors or key players in disease pathogenesis. Generally, the existing data demonstrate that H2S possesses neuroprotective effects upon exposure to endogenous (amyloid ß, glucose, and advanced-glycation end-products, homocysteine, lipopolysaccharide, and ammonia) and exogenous (alcohol, formaldehyde, acrylonitrile, metals, 6-hydroxydopamine, as well as 1-methyl-4-phenyl- 1,2,3,6- tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenyl pyridine ion (MPP)) neurotoxicants. On the one hand, neuroprotective effects are mediated by S-sulfhydration of key regulators of antioxidant (Sirt1, Nrf2) and inflammatory response (NF-κB), resulting in the modulation of the downstream signaling, such as SIRT1/TORC1/CREB/BDNF-TrkB, Nrf2/ARE/HO-1, or other pathways. On the other hand, H2S appears to possess a direct detoxicative effect by binding endogenous (ROS, AGEs, Aß) and exogenous (MeHg) neurotoxicants, thus reducing their toxicity. Moreover, the alteration of H2S metabolism through the inhibition of H2S-synthetizing enzymes in the brain (CBS, 3-MST) may be considered a significant mechanism of neurotoxicity. Taken together, the existing data indicate that the modulation of cerebral H2S metabolism may be used as a neuroprotective strategy to counteract neurotoxicity of a wide spectrum of endogenous and exogenous neurotoxicants associated with neurodegeneration (Alzheimer's and Parkinson's disease), fetal alcohol syndrome, hepatic encephalopathy, environmental neurotoxicant exposure, etc. In this particular case, modulation of H2S-synthetizing enzymes or the use of H2S-releasing drugs should be considered as the potential tools, although the particular efficiency and safety of such interventions are to be addressed in further studies.

Valores de referencia para plumbemia em uma populacao urbana do Sul do Brasil / Reference values for lead in blood in an urban population in southern Brazil

Objetive. To describe the reference values for lead in blood in an urban population in the city of Londrina, in the state of Paraná, Brasil. Materials and methods. The reference population was composed of 520 adult volunteers who were assessed from November 1994 to December 1996. Exclusion criteria were: occupational exposure to lead, exposure through personal habits or practice, smoking more than 10 cigarettes per day, and living near indistrial plants or other places that use lead in the production processes. Also excluded were individuals with abnormal clical or laboratory results or with chonic diseases or cardiovascular disorders. Lead blood levels were determined using air-acetylene flame atomic absorption spectrophotometry. The detectable limit was 1.23ug/dL. After the analyses of lead in blood, the following values were determined: minimum value, first quartile, median, third quartile, and maximum value; geometric mean, 95 confidence interval; experimental interval; and reference value. Results. The reference values for lead in blood ranger from 1.20ug/dL to 13.72ug/dL. The geometric mean was 5.5 ug/dL. Conclusions. In general, the values found in this study are lower than those that have been reported for other countries. Additional date should be gathered from Brazilian populations living in more-industrialized areas