Complex roles for sulfation in the toxicities of polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are persistent organic toxicants derived from legacy pollution sources and their formation as inadvertent byproducts of some current manufacturing processes. Metabolism of PCBs is often a critical component in their toxicity, and relevant metabolic pathways usually include their initial oxidation to form hydroxylated polychlorinated biphenyls (OH-PCBs). Subsequent sulfation of OH-PCBs was originally thought to be primarily a means of detoxication; however, there is strong evidence that it may also contribute to toxicities associated with PCBs and OH-PCBs. These contributions include either the direct interaction of PCB sulfates with receptors or their serving as a localized precursor for OH-PCBs. The formation of PCB sulfates is catalyzed by cytosolic sulfotransferases, and, when transported into the serum, these metabolites may be retained, taken up by other tissues, and subjected to hydrolysis catalyzed by intracellular sulfatase(s) to regenerate OH-PCBs. Dynamic cycling between PCB sulfates and OH-PCBs may lead to further metabolic activation of the resulting OH-PCBs. Ultimate toxic endpoints of such processes may include endocrine disruption, neurotoxicities, and many others that are associated with exposures to PCBs and OH-PCBs. This review highlights the current understanding of the complex roles that PCB sulfates can have in the toxicities of PCBs and OH-PCBs and research on the varied mechanisms that control these roles.

Zinc Phenolsulfonate.

The Expert Panel for Cosmetic Ingredient Safety reviewed newly available studies since their original assessment in 1986 and a previous re-review in 2004, along with updated information regarding product types and concentrations of use. Considering this information, the Panel confirmed that Zinc Phenolsulfonate is safe as a cosmetic ingredient in the present practices of use and concentration as described in this report.

Toxic potential assessment of hair dye developer 2,4,5,6-tetraaminopyrimidine sulfate exposed under ambient UVB radiation.

Synthetic cosmetics, particularly hair dyes, are becoming increasingly popular among people of all ages and genders. 2,4,5,6-tetraaminopyrimidine sulfate (TAPS) is a key component of oxidative hair dyes and is used as a developer in several hair dyes. TAPS has previously been shown to absorb UVB strongly and degrade in a time-dependent manner, causing phototoxicity in human skin cells. However, the toxic effects of UVB-degraded TAPS are not explored in comparison to parent TAPS. Therefore, this research work aims to assess the toxicity of UVB-degraded TAPS than TAPS on two different test systems, that is, HaCaT (mammalian cell) and Staphylococcus aureus (a bacterial cell). Our result on HaCaT has illustrated that UVB-degraded TAPS is less toxic than parent TAPS. Additionally, UVB-exposed TAPS and parent TAPS were given to S. aureus, and the bacterial growth and their metabolic activity were assessed via CFU and phenotype microarray. The findings demonstrated that parent TAPS reduced bacterial growth via decreased metabolic activity; however, bacteria easily utilized the degraded TAPS. Thus, this study suggests that the products generated after UVB irradiation of TAPS is considered to be safer than their parent TAPS.

Sulfate sensitivity of aquatic organism in soft freshwaters explored by toxicity tests and species sensitivity distribution.

Elevated concentrations of sulfate in waterways are observed due to various anthropogenic activities. Elevated levels of sulfate can have harmful effects on aquatic life in freshwaters: sulfate can cause osmotic stress or specific ion toxicity in aquatic organisms, especially in soft waters where Ca2+ and Mg2+ concentrations are low. Formerly, chronic toxicity test data in soft water have been scarce. The chronic and acute sulfate toxicity tests conducted with aquatic organisms from 10 families across various trophic levels in this study multiplied the number of tests conducted in soft freshwater conditions and enabled derivation of the species sensitivity distribution (SSD) and sulfate hazardous concentrations for soft freshwaters. The cladoceran Daphnia longispina and freshwater snail Lymnaea stagnalis were the most sensitive to sulfate among the studied species. Harmful effects on the reproduction of D. longispina were observed at 49 mg SO4 /L while growth of L. stagnalis was inhibited at 217 mg SO4 /L. Most studied organisms tolerated high sulfate concentrations: the median of chronic effective concentrations (EC10 or LC10) was 1008 mg/L for all the species tested in this study. Based on the species sensitivity distribution of the studied species the hazardous concentration for 5 % of aquatic organism (HC5) in soft waters was 117-194 mg SO4/L. Different data set combinations were used to demonstrate the data variability in SSD-based HC5 estimates. The lowest values were produced from combining biotest results from the present study and earlier literature, while the highest values were calculated from the present study only. The derived chronic no-effect concentrations (PNEC) varied between 39 and 65 mg SO4/L.

Investigating and modeling the toxicity of arsenate on wheat root elongation: Assessing the effects of pH, sulfate and phosphate.

Excessive arsenic in soil and groundwater will not only seriously affect the growth of plants, but also endanger human health through the food chain. However, there are few studies on the effects of metalloid speciation and anion competition on the toxicity of arsenate [As(Ⅴ)]. To investigate the effects of accompanying anions and pH on the toxicity of As(Ⅴ) on wheat root elongation, wheat roots were exposed to the concentrations of As(Ⅴ) in the solution ranged from 0 to 500 mM and different levels of pH (4.5-8.0) and different accompanying anions (H2PO4-, SO42-, NO3- and Cl-) for five days. The root length of wheat was measured and the biotic ligand model (BLM) was developed to predict the potential toxicity of As(V) speciation to wheat roots. The results illustrated that EC50 of total As(V) (EC50{As(Ⅴ)T}) values increased from 6.88 to 33.9 µM with increasing pH values from 4.5 to 8.0, suggesting that increasing pH alleviated As(Ⅴ) toxicity. The EC50{AsO43-} and EC50{HAsO42-} values increased from 0.001 to 4342 µM and from 0.0214 to 27.4 µM, respectively, while the EC50{H2AsO4-} and EC50{H3AsO4} values sharply decreased from 6.62 to 2.68 µM and from 41.8 µM to 5.34 nm, respectively, when pH increased from 4.5 to 8.0. The toxicity of As(Ⅴ) decreased as the H2PO4- and SO42- activities increased but not when the activities of NO3- and Cl- increased, indicating that SO42- and H2PO4- showed competitive effects with As(Ⅴ) on the binding sites. Based on BLM theory, the stability constants were obtained: [Formula: see text] = 3.70; [Formula: see text] = 4.08; [Formula: see text] = 4.77; [Formula: see text] = 6.50; [Formula: see text] = 2.09 and [Formula: see text] = 1.86, with fAsBL50%= 0.30 and ß = 1.73. Results implied that BLM performed well in As(Ⅴ) toxicity prediction when coupling toxic species AsO43-, HAsO42-, H2AsO4-, and H3AsO4, and the competition of SO42- and H2PO4- for binding sites. The current study provides a useful tool to accurately predict As(V) toxicity to wheat roots.

Lithium influences whole-organism metabolic rate in Drosophila subobscura.

Lithium is widely used to treat bipolar disorder. However, the efficacy and vulnerability as to its side effects are known to differ. Although the specific biochemical mechanism of action is still elusive, lithium may influence mitochondrial function, and consequently, metabolism. Lithium exposure in this study was conducted on a unique set of mito-nuclear introgression lines of Drosophila subobscura to disentangle the independent effects of mitochondrial DNA (mtDNA) against a common nuclear DNA background. The study addressed three issues: (a) whether lithium has a dose-dependent effect on whole-organism metabolic rate, (b) whether mtDNA haplotypes show divergent metabolic efficiency measured by metabolic rate to lithium exposure and (c) whether lithium influences the whole-organism metabolic rate across sexes. The results confirm that lithium influenced the whole-organism metabolic rate, showing a subtle balance between efficacy and adverse effects within a narrow dose range. In addition, lithium exposure was found to influence metabolism differently based on mtDNA haplotypes and sex. This preliminary research may have a range of biological implications for the role of mitochondrial variability in psychiatric disease and treatment by contributing to the understanding and predicting of the lithium treatment response and risk for toxic side effects.

Sulfate conjugation may be the key to hepatotoxicity in paracetamol overdose.

Paracetamol-induced hepatotoxicity is the leading cause of acute liver failure in many countries, including North America and the United Kingdom. Among the three dominant paracetamol metabolism pathways (i.e. glucuronidation, sulfation and oxidation), the importance of sulfation is often underestimated because of the general thinking that the sulfation pathway is saturated at therapeutic doses and ultimately accounts for a limited proportion of the fate of a paracetamol dose. We illustrate that insufficient sulfation leads to a shift in biotransformation of paracetamol to toxic oxidation pathways and patients with low sulfate reserves are at higher risk of paracetamol toxicity. Here, we propose that sulfation is of critical importance in understanding the risk of liver toxicity secondary to paracetamol overdose. Serum inorganic sulfate, a measurable substrate on the causal path of paracetamol-induced liver toxicity, should be considered a biomarker for potential toxicity as well as a target for treatment.

Sulfate toxicity to early life stages of European whitefish (Coregonus lavaretus) in soft freshwater.

Sulfate occurs naturally in the aquatic environment but its elevated levels can be toxic to aquatic life in freshwater environments. We investigated the toxicity of sulfate in humic, soft freshwater to whitefish (Coregonus lavaretus) from fertilization of eggs to hatching i.e. during the critical phases of whitefish early development. Anadromous Kokemäenjoki whitefish eggs and sperm during fertilization, embryos and larvae were exposed in the long-term 175-day incubation to seven different sodium sulfate (Na2SO4) concentrations from 44 to 2 000 mg SO4 L-1. Endpoint variables were the fertilization success, offspring survival and larval growth. Egg fertilization and early embryonic development were the most sensitive developmental stages of whitefish to sulfate, although the fertilization success and survival of embryos decreased only in the highest concentration of 2 000 mg SO4 L-1. The survival during late embryonic period, hatching and the 5-day larval period was high and no difference between the control and sulfate treatments were observed. LC50-values of sulfate for early embryonic period and for the entire embryonic and larval period was 1 413 and 1 161 mg L-1, respectively. The NOEC (No-observed Effect Concentration) of sulfate for the both periods was 1 207 mg L-1. The tolerance of whitefish early stages to sulfate toxicity seems to be on the same level as the tolerance of other salmonids' early stages.

Final Amended Safety Assessment of Sodium Sulfate as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reopened the safety assessment of Sodium Sulfate, a cosmetic ingredient that is an inorganic salt reported to function in cosmetics as a viscosity increasing agent-aqueous. The Panel reviewed the relevant new data for the ingredient, including frequency of use and concentration of use, and considered data from the previous Panel assessment. The Panel concluded that Sodium Sulfate is safe in cosmetics in the present practices of use and concentrations described in this safety assessment when formulated to be nonirritating.

Effect of carbon source and metal toxicity for potential acid mine drainage (AMD) treatment with an anaerobic sludge using sulfate-reduction.

This study compares sulfate-reduction performance in an anaerobic sludge with different carbon sources (ethanol, acetate, and glucose). Also, the toxic effect of copper was evaluated to assess its feasibility for possible acid mine drainage (AMD) treatment. Serological bottles with 1.5 g VSS/L and 150 mL of basal medium (0.67 g COD/g SO42- at a 7-8 pH) were used to determine the percentage of electron equivalents, maximum specific methanogenic (SMA), and sulfide generation activities (SGA). The copper effect was evaluated in a previously activated sludge in batch bioassays containing different concentrations of copper (0-50 mg/L), 3 gVSS/L, and 150 mL of basal medium (0.67 g COD/g SO42-). Carbon source bioassays with glucose obtained the best results in terms of the SGA (1.73 ± 0.34 mg S2-/g VSS•d) and SMA (10.41 mg COD-CH4/g VSS•d). The electron flow in the presence of glucose also indicated that 21.29 ± 5.2% of the metabolic activity of the sludge was directed towards sulfidogenesis. Copper toxicity bioassays indicated that a considerable decline in metabolic activity occurs above 10 mg/L. The 20%IC, 50%IC, and 80%IC were 4.5, 14.94, and 35.31 mg Cu/L. Compared to the other carbon sources tested, glucose proved to be a suitable electron donor since it favors sulfidogenesis. Finally, copper concentrations above 15 mg/L inhibited metabolic activity in the toxicity bioassays.

Simulated sulfuric and nitric acid rain inhibits leaf breakdown in streams: A microcosm study with artificial reconstituted fresh water.

Acid rain containing SO42- and NO3- in China has been a public concern for decades. However, a decrease of SO2 has been recorded since the government enacted a series of policies to control its emission. To comprehensively evaluate the consequence of realistic and future acid deposition scenarios, this study explored the effects of mixed acid rain with different molar ratios of SO42- and NO3- (0:1, 1:0, 2:1, 1:1, and 1:2) on stream leaf breakdown through a microcosm experiment. A significant inhibition of leaf breakdown rate was observed when the ratio was 1:2 with reduced microcosm pH, fungal biomass, enzyme activities as well as the frequencies of hub general in the fungal community. In conclusion, the ratio of SO42- and NO3- in acid rain was an important factor that could have a profound impact on leaf breakdown, even on ecosystem structure and functioning of streams.

Theoretical investigation on the contribution of HO, SO4- and CO3- radicals to the degradation of phenacetin in water: Mechanisms, kinetics, and toxicity evaluation.

Indirect oxidation induced by reactive free radicals, such as hydroxyl radical (HO), sulfate radical (SO4-) and carbonate radical (CO3-), plays an important or even crucial role in the degradation of micropollutants. Thus, the coadjutant degradation of phenacetin (PNT) by HO, SO4- and CO3-, as well as the synergistic effect of O2 on HO and HO2 were studied through mechanism, kinetics and toxicity evaluation. The results showed that the degradation of PNT was mainly caused by radical adduct formation (RAF) reaction (69% for Г, the same as below) and H atom transfer (HAT) reaction (31%) of HO. For the two inorganic anionic radicals, SO4- initiated PNT degradation by sequential radical addition-elimination (SRAE; 55%), HAT (28%) and single electron transfer (SET; 17%) reactions, while only by HAT reaction for CO3-. The total initial reaction rate constants of PNT by three radicals were in the order: SO4- > HO > CO3-. The kinetics of PNT degradation simulated by Kintecus program showed that UV/persulfate could degrade target compound more effectively than UV/H2O2 in ultrapure water. In the subsequent reaction of PNT with O2, HO and HO2, the formation of mono/di/tri-hydroxyl substitutions and unsaturated aldehydes/ketones/alcohols were confirmed. The results of toxicity assessment showed that the acute and chronic toxicity of most products to fish increased and to daphnia decreased, and acute toxicity to green algae decreased while chronic toxicity increased.

Physicochemical and Toxicological Assay of Leachate from Malt Spent Rootlets Biochar.

The aim of this study was to characterize the leachate derived from biochar produced from malt spent rootlets (MSR) and to evaluate the required washing level in order to provide water free from inorganic substances. MSR biochar was placed in a column and subjected to six serial washes with distilled water, and the leachate was analysed for main anions and heavy metals. The 1st wash aliquot contained increased levels of mainly phosphates (980 mg/L) and chlorides (760 mg/L), and lower levels of nitrates, sulfates, fluoride and bromide, which were decreased over washes. Zero concentrations were observed after three washes for most anions. The increased levels of Zn, Be, Cs, Mn, V and Se determined in the 1st wash aliquot were eliminated in the successive washes. The toxic potency of each wash aliquot, determined by the use of the fairy shrimp Thamnocephalus platyurus showed that the 1st and 2nd MSR biochar leachates were toxic with 4.52 and 1.46 toxic units (TU), respectively, followed by a significant elimination of toxicity after further washes.

Assessment of Fish Embryo Survival and Growth by In Situ Incubation in Acidic Boreal Streams Undergoing Biomining Effluents.

The applicability of an in situ incubation method in monitoring the effects of metal mining on early life stages of fish was evaluated by investigating the impacts of a biomining technology utilizing mine on the mortality, growth, and yolk consumption of brown trout (Salmo trutta) and whitefish (Coregonus lavaretus) embryos. Newly fertilized eggs were incubated from autumn 2014 to spring 2015 in six streams under the influence of the mine located in North-Eastern Finland and in six reference streams. Although the impacted streams clearly had elevated concentrations of several metals and sulfate, the embryonic mortality of the two species did not differ between the impacted and the reference streams. Instead, particle accumulation to some cylinders had a significant impact on the embryonic mortality of both species. In clean cylinders, mortality was higher in streams with lower minimum pH. However, low pH levels were evident in both the reference and the mine-impacted groups. The embryonic growth of neither species was impacted by the mining activities, and the growth and yolk consumption of the embryos was mainly regulated by water temperature. Surprisingly, whitefish embryos incubated in streams with lower minimum pH had larger body size. In general, the applied in situ method is applicable in boreal streams for environmental assessment and monitoring, although in our study, we did not observe a specific mining impact differing from the effects of other environmental factors related to catchment characteristics.

Systemic administration of l-kynurenine sulfate induces cerebral hypoperfusion transients in adult C57Bl/6 mice.

The kynurenine pathway is a cascade of enzymatic steps generating biologically active compounds. l-kynurenine (l-KYN) is a central metabolite of tryptophan degradation. In the mammalian brain, l-KYN is partly converted to kynurenic acid (KYNA), which exerts multiple effects on neurotransmission. Recently, l-KYN or one of its derivatives were attributed a direct role in the regulation of the systemic circulation. l-KYN dilates arterial blood vessels during sepsis in rats, while it increases cerebral blood flow (CBF) in awake rabbits. Therefore, we hypothesized that acute elevation of systemic l-KYN concentration may exert potential effects on mean arterial blood pressure (MABP) and on resting CBF in the mouse brain. C57Bl/6 male mice were anesthetized with isoflurane, and MABP was monitored in the femoral artery, while CBF was assessed through the intact parietal bone with the aid of laser speckle contrast imaging. l-KYN sulfate (l-KYNs) (300mg/kg, i.p.) or vehicle was administered intraperitoneally. Subsequently, MABP and CBF were continuously monitored for 2.5h. In the control group, MABP and CBF were stable (69±4mmHg and 100±5%, respectively) throughout the entire data acquisition period. In the l-KYNs-treated group, MABP was similar to that, of control group (73±6mmHg), while hypoperfusion transients of 22±6%, lasting 7±3min occurred in the cerebral cortex over the first 60-120min following drug administration. In conclusion, the systemic high-dose of l-KYNs treatment destabilizes resting CBF by inducing a number of transient hypoperfusion events. This observation indicates the careful consideration of the dose of l-KYN administration by interpreting the effect of kynurenergic manipulation on brain function. By planning clinical trials basing on kynurenergic manipulation possible vascular side effects should also be considered.

Sulfate Aerosols Promote Lung Cancer Metastasis by Epigenetically Regulating the Epithelial-to-Mesenchymal Transition (EMT).

Secondary inorganic aerosols (SIA), particularly sulfate aerosols, are central particulate matter (PM) constituents of severe haze formation in China and exert profound impacts on human health; however, our understanding of the mechanisms by which sulfate aerosols cause malignancy in lung carcinogenesis remains incomplete. Here, we show that exposure to secondary inorganic aerosols induced the invasion and migration of lung epithelial cells, and that (NH4)2SO4 exerted the most serious effects in vitro and promoted lung tumor metastasis in vivo. This action was associated with alterations of phenotype markers in the epithelial-to-mesenchymal transition (EMT), such as the up-regulation of fibronectin (Fn1) and the down-regulation of E-cadherin (E-cad). Hypoxia-inducible factor 1α (HIF-1α)-Snail signaling, regulated by the generation of reactive oxygen species (ROS), was involved in the (NH4)2SO4-induced EMT, and the potent antioxidant N-acetylcysteine (NAC) inhibited the activation of HIF-1α-Snail and blocked the EMT, cell invasion, and migration in response to (NH4)2SO4. Additionally, CpG hypermethylation in the E-cad promoter regions partly contributed to the (NH4)2SO4-regulated E-cad repression, and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-Aza) restored the (NH4)2SO4-induced down-regulation of E-cad. Our findings reveal a potential mechanistic basis for exploring the association between sulfate aerosol exposure and increased malignancy during lung carcinogenesis, and suggest new approaches for the treatment, improvement, and prevention of lung cancer resulting from sulfate aerosol exposure in severe haze-fog.

Comparative Developmental Toxicity of Desalination Brine and Sulfate-Dominated Saltwater in a Euryhaline Fish.

Desalination is a promising sustainable solution to meet growing water needs of cities across the United States. However, the environmental impacts of the resulting filtrate (brine) discharged to surface water need to be evaluated before large-scale desalination can be successful in the United States. Developing fish are especially sensitive to changes in salinity and varying ionic composition. Limited research is available on the impacts of hypersalinity on chronic vertebrate embryonic development, particularly on sublethal effects. To investigate this, Japanese medaka (Oryzias latipes) embryos were treated with: (1) graphite filtered freshwater; (2) artificial seawater [17, 35, 42, 56, and 70 parts per thousand (ppt)]; (3) effluent from a desalination facility at Monterey Bay Aquarium, CA, diluted to 75, 50, and 25% with 35 ppt artificial seawater to simulate mixing (39, 42, 46, and 50 ppt); (4) artificial San Joaquin River water (CA, USA) (9, 13, and 17 ppt); and (5) artificial San Joaquin River water diluted to 75, 50, and 25% with artificial seawater to simulate estuarine mixing in the San Francisco Bay (13, 19, 24, and 30 ppt). Percent hatch, survival post hatch, deformities, swim bladder inflation, and median day to hatch were recorded to calculate EC50 (50% effect concentration) and NOEC (no observable effect concentration) values. No significant difference was observed between artificial seawater and Monterey Bay aquarium effluent (EC50 = 45-55 ppt). However, San Joaquin River water decreased survival post hatch and increased deformities in comparison to artificial seawater and San Joaquin River water mixed with seawater, suggesting that unique ion compositions may play a role in embryo and larval toxicity.

De novo assembly and analysis of changes in the protein-coding transcriptome of the freshwater shrimp Paratya australiensis (Decapoda: Atyidae) in response to acid sulfate drainage water.

BACKGROUND: The atyid shrimp Paratya australiensis occurs in surface freshwater habitats throughout eastern Australia and has been used to study the ecotoxicology of contaminants such as pesticides and metals. The acidification of surface water that can occur after acid sulfate material in soils and sediments is oxidised and subsequently re-wetted is a serious environmental issue in coastal regions and inland riverine floodplains worldwide. Solubilisation of soil-associated minerals can result in high waterborne concentrations of mineral salts and dissolved metals, which together with low pH represent a potential threat to aquatic ecosystems in affected regions. The aims of the present study were to gain insight into stress responses induced by exposure to acid drainage water (ADW) in P. australiensis by determining changes in the abundance of protein-coding transcripts and to generate a comprehensive transcriptomic resource to facilitate further research into gene regulation or protein structure and function in this species. Adult P. australiensis were exposed for 24 h to undiluted ADW, 50 % ADW diluted in river water, or to river water as control, and high-throughput mRNA sequencing (RNA-Seq) conducted on whole-body tissues. A reference transcriptome was generated using de novo assembly and putative protein-coding regions were identified and annotated. Changes in transcript abundance in response to ADW exposure were determined by aligning reads to the reference transcriptome and quantifying coverage. RESULTS: A high proportion of arthropod benchmarking universal single-copy orthologues were present in the reference transcriptome. Functions associated with cuticle biosynthesis and oxidative stress were significantly enriched in the lists of transcripts exhibiting differential abundance in either direction after exposure to 50 % or 100 % ADW. Transcripts involved in osmoregulation exhibited decreased abundance following exposure to ADW. The transcriptome contained full-length coding sequences for numerous proteins known to be involved in environmental response pathways, including two putative metallothioneins, four glutathione peroxidases and 19 nuclear receptors. CONCLUSIONS: The results of the present study provide insight into stress response pathways induced in crustaceans by short-term exposure to multiple stressors present in ADW such as low pH, high salinity and dissolved metals, and represent a resource for future toxicogenomics and protein functional studies in P. australiensis.

Critical roles of TIPE2 protein in murine experimental colitis.

Both commensal bacteria and infiltrating inflammatory cells play essential roles in the pathogenesis of inflammatory bowel disease. The molecular mechanisms whereby these pathogenic factors are regulated during the disease are not fully understood. We report in this article that a member of the TNF-α-induced protein 8 (TNFAIP8) family called TIPE2 (TNFAIP8-like 2) plays a crucial role in regulating commensal bacteria dissemination and inflammatory cell function in experimental colitis induced by dextran sodium sulfate (DSS). Following DSS treatment, TIPE2-deficient mice, or chimeric mice that are deficient in TIPE2 only in their hematopoietic cells, lost less body weight and survived longer than wild-type controls. Consistent with this clinical observation, TIPE2-deficient mice exhibited significantly less severe colitis and colonic damage. This was associated with a marked reduction in the colonic expression of inflammatory cytokines, such as TNF-α, IL-6, and IL-12. Importantly, the ameliorated DSS-induced colitis in TIPE2(-/-) mice also was associated with reduced local dissemination of commensal bacteria and a weaker systemic inflammatory response. Combined with our previous report that TIPE2 is a negative regulator of antibacterial immunity, these results indicate that TIPE2 promotes colitis by inhibiting mucosal immunity to commensal bacteria.

Chronic exposure to manganese sulfate leads to adverse dose-dependent effects on the neurobehavioral ability of rats.

Manganese sulfate is the main combustion product of methylcyclopentadienyl manganese tricarbonyl (MMT). Currently, little is known about the neurobehavioral consequences of chronic manganese sulfate exposure. In this study, rats were treated with 0, 5.0, 10.0, and 20.0 mg/kg MnSO4 ·H2 O for 24 consecutive weeks via intraperitoneal injection. During the treatment period, spatial learning-memory ability was measured using the Morris water maze (MWM). At the end of the exposure period, spontaneous motor behavior and emotional status, hippocampal histologic changes, and Hsp70 mRNA levels were measured using the open-field test (OFT), hematoxylin-eosin staining and real-time quantitative PCR (RT-PCR), respectively. A dose-dependent decrease was noted in the spatial learning-memory ability and the spontaneous activities of rats (P < 0.05), and negative emotions differed significantly between the exposed groups and the control group (P < 0.05). Moreover, overt morphological changes in the hippocampuses of the exposed rats were detected. Cellular degeneration and death were also found. The Hsp70 mRNA levels of the hippocampal areas in the 20.0 mg/kg group (1.567 ± 0.236) were significantly increased compared with the control group (P < 0.05). These results suggest that chronic exposure to manganese sulfate can have adverse dose-dependent effects on rats' neurobehavioral ability, and the mechanism of abnormal hippocampal Hsp70 expression needs to be further explored. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1571-1579, 2016.