SO2 是一种常见的全球性大气环境污染物，前期研究提示其不仅能引起呼吸道疾患，极有可能还与一些中枢神经系统疾病的发生有关，但后者的分子机制尚不清楚。为此，本文采用动式熏气法研究了不同浓度SO2（7、14、28 和56mg/m3）吸入对大鼠海马组织炎性因子白介素-1β（IL-1β）和肿瘤坏死因子（TNF-α）水平、神经元胞内游离Ca2+浓度，即早基因（c-fos，c-jun 和COX-2）和凋亡相关基因（bcl-2，bax 和p53）表达的影响。结果表明：SO2 可造成海马组织IL-1β 和TNF-α水平显著增高，但低浓度下（7、14mg/m3）作用较为明显；SO2 可显著增加神经 元胞内钙离子浓度，上调即早基因c-fos，c-jun 和COX-2，凋亡基因bcl-2，bax和p53 mRNA 及其蛋白表达，且呈现出明显的剂量-效应关系，其中对COX-2 基因表达的作用最为明显。这一结果从整体水平上说明了SO2 对中枢神经系统的损伤效应，并提示其分子机制可能涉及炎性反应、钙离子稳态、即早基因和凋亡基 因表达。

In the present study, protein oxidation (PCO content) and DNA-protein crosslinks (DPC coefficient) were investigated in the viscera of mice exposed to a municipal landfill leachate at various concentrations for 7 days. The study was designed to investigate the injuries and a possible mechanism of landfill leachateinduced toxicity on mammals. The results indicate that the leachate sample changed the ratio of viscera to body weight in all organs tested, and the effect on the brain was more obvious than that on other organs. The leachate ingestion increased PCO levels in the brain, kidney, liver and spleen in a concentrationdependent manner, but did not affect the content in the heart. Also, the leachate sample enhanced DPC formation in the tested organs in a concentration-dependent manner, and the responses of the liver, kidney and spleen were more sensitive than that of the brain and heart. These findings provide further evidence that landfill leachate-induced toxicity on mammals might involve the formation of free radicals, either via autoxidation or by enzyme-catalyzed oxidation of pollutants in leachate, and then attack of proteins and nucleic acids via generated free radicals.

Recent studies implicate the possible neurotoxicity of SO2, wever, its mechanisms remain unclear. In the present study, we investigated SO2 derivative-induced effect on delayed rectifier potassium channels(IK) and cellular death/apoptosis in primary cultured hippocampal neurons. The results demonstrate that SO2 derivatives (NaHSO3 and Na2SO3, 3:1M/M) effectively augmented IK and promoted the activation of delayed rectifier potassium channels. Also, SO2 derivatives increased neuronal death percentage and contributed to the formation of DNA ladder in concentration-dependent manners. Interestingly, the neuronal death and DNA ladder formation, caused by SO2 derivatives, could be attenuated by the delayed rectifier potassium channel blocker (tetraethylammonium, TEA), but not byt het ransient outward potassium channel blocker(4-aminopyridine, 4-P). It implies that stimulating delayed rectifier potassium channels were involved in SO2 derivative-caused hippocampal neuronal insults, and blocking these channels might be one of the possibly clinical treatment for SO2-caused neuronal dysfunction.

Previous studiesprovideevidenceforthepossibleneurotoxicityof SO2, butlittleinformationis availableaboutitsmechanisms. Inthepresentstudy, SO2 inhalation-inducedeffectsontheprotein oxidation, DNA-proteincrosslinksandapoptosisinrathippocampuswerestudied, byexposingWistar rats to SO2 at 14, 28and56mg/m3. Theresultsindicatethattheproteincarbonylcontent, anindicatorof proteinoxidation, andDNA–proteincrosslinkcoefficientweresignificantlyaugmented with concentration-dependentproperties. Inaddition, SO2 inhalationatallconcentrationstestedcaused the increasesofcaspase-3activityandnumberofTUNELpositivestainingneuronandthestatistical difference asobservedafter28and56mg/m3 exposure, suggestingtheoccurrenceofapoptosis. The results implythatattackingprotein, nucleicacidsandlipidsbyfreeradicals, generatedvia SO2 derivatives in vivo, isoneofthemainmechanismsfor SO2-inducedinjuriesincentralneuronalsystem

The effects of the Xingou municipal landfill leachate on levels of thiobarbituric acid reactive substances (TBARS) and the activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD), Se-dependent glutathione peroxidase (Se-dependent GPx), and catalase (CAT) were investigated in brains and livers of Kunming albino mice of both sexes, using chemical oxygen demand (CODCr) as ameasure of leachate concentration. The results show that leachate caused lipid peroxidation and change of antioxidative status in brains and livers of mice. There was a sex difference in the response of antioxidative status, and female mice were more sensitive than male mice. Exposure to leachate at all concentrations tested caused significant increases of TBARS levels in brains and livers from mice of both sexes. For brains, Cu,Zn-SOD and Se-dependent GPx activities were significantly increased at high concentration (CODCr 240mg/L) for male mice, but the activities of both antioxidative enzymes were significantly increased at low concentration (CODCr 60mg/L) and decreased at high concentration (CODCr 240mg/L) for female mice; CAT activities remained unchanged for male mice and were significantly decreased for female mice at high concentration (CODCr 240mg/L). For livers, Cu,Zn-SOD and Se-dependent GPx activities were significantly increased at high concentrations (CODCr 120 and 240mg/L) for male mice, but the activities of both antioxidative enzymes were significantly increased at low concentration (CODCr 30 or 60mg/L) and decreased at high concentration (CODCr 240mg/L) for female mice; CAT activities were significantly increased for male mice at all concentrations tested and decreased for female mice at high concentrations (CODCr 120 and 240mg/L). These results suggest that leachate exposure can cause oxidative damage on brains and livers of mice. The results also suggest that leachate might induce toxicity in mammals by the free-radical-damage mechanism.