Generational effects and abnormalities in craniofacial chondrogenesis in zebrafish (Danio rerio) embryos upon maternal exposure to estrogen endocrine disrupting chemicals.

Bisphenol A (BPA) and diethyl phthalate (DEP) are estrogenic endocrine disrupting chemicals (EEDCs). The present study reconfirmed that the angle of the ceratohyal cartilage (CH) in embryos were larger from maternal BPA and E2, but smaller from DEP compared to the control. However, it is still unknown whether both the BPA and DEP chemicals disrupted the action of E2 and thereby influence the estrogen signaling pathways. Additionally, it remains unclear whether they also disrupted certain related genes in the migratory pathways of neural crest cells (NCCs) in their offspring. The present data showed that nuclear estrogen receptors and membrane estrogen receptors have different disrupted profiles among female zebrafish exposed to BPA (F-BPA), and DEP (F-DEP), and external E2 (F-E2). However, certain related genes in the migratory pathways of NCCs in embryos from F-BPA and F-E2 such as the sox10, chm1, and tgfbr1a mRNA expressions showed a positive relationship compared with CH angles; the gene expressions of sox9a, smad3, and col2a1a and the CH angles of embryos exhibited an opposite relationship upon F-DEP treatments. Thus, we suggested that the genes involved in NCCs migration were potentially induced by the residual maternal DEP contents. Two sets of genes, chm1/tgfb3 and chm1/gper1, exhibited an identical profile in the ovary and its offspring at 2 h of post fertilization upon F-E2 and F-BPA treatments, respectively. We suggested that the maternal mRNA from female to embryos were transferred before the maternal-to-zygotic transition stage.

Reproductive and Developmental Alterations on Zebrafish (Danio rerio) Upon Long-Term Exposure of Di-ethyl phthalate (DEP), Di-isononyl phthalate (DINP) and Di (2-ethylhexyl) phthalate (DEHP).

Di (2-ethylhexyl) phthalate (DEHP), di-ethyl phthalate (DEP) and di-isononyl phthalate (DINP) are all endocrine disrupting chemicals (EDCs) for organisms. However, little research has been done on the effects of long-term EDC exposure. The present study found that the zebrafish barely grew during the 7 months of DINP exposure. The fecundity rate (%) of female spawning was lower in the DEHP treatment by 4 months compared to other exposure groups. Zebrafish treated with 12.5-25.0 ppm of DEP for 4 months presented no spawning. Gonadal-somatic index (GSI) levels significantly decreased, and there were more oocytes in the atresia and peri-nucleus stage compared to the control group. In addition, the hatching rate of embryos were 71.02%, 56.92%, and 21.70% for females treated with DINP, DEHP and DEP, respectively. There were also abnormal craniofacial chondrogenesis development on 72 hpf embryos upon females treated with the three EDCs. In conclusion, long term exposure of DEHP, DINP, and DEP did not only affect the reproductive capacity of female zebrafish, but the 3 plasticizers also influence craniofacial cartilage development of its offspring.

Duration of Induced Metallothionein is a Critical Factor in the Cadmium-Resistance Among Goldfish (Carassius auratus) and Common Carp (Cyprinus carpio).

According to the Environmental Protection Agency in Taiwan, the common carp (Cyprinus carpio) is one species of fish for acute toxic test. It has been found to be extremely sensitive to the toxicity of Cd2+; Furthermore, the goldfish (Carassius auratus) has a higher resistance than common carp upon Cd2+ exposure, but both fish are the same family. The aim of the study was to compare the physiological and histo-pathological responses between goldfish and common carp under exposure to sublethal concentrations of Cd2+ in order to understand the reasons behind the Cd2+-resistance. Results showed that metallothionein (MT) protein levels in visceral tissues were exceptionally increased and elevated at an earlier time in goldfish than in common carp. Meanwhile, the amount of Cd2+ accumulation in goldfish was higher than common carp after Cd2+ exposure. The histo-pathological results revealed that the density of gill mucus cells and the thickness of gill epithelium in common carp were raised earlier than in goldfish, but the histo-pathological findings resemble each other. According to the data, we suggested the efficient response of MT proteins may contribute to goldfish with a higher Cd2+ tolerance.

Maternal effect and dietary supplementation of estradiol-17ß on female zebrafish (Danio rerio) affects the swimming behavior and stress-coping styles of its offspring.

Extrinsic estradiol-17ß (E2) is an environmental hormone. Female fish exposure to waterborne E2 might affect the development of craniofacial cartilage of its offspring. The present study investigates the effects of maternal E2 on larval craniofacial cartilage development by administering oral feed containing E2 (F-E2) to female zebrafish, and examines whether the swimming behavior and their stress coping style are influenced by maternal E2. The results showed that E2 contents responded to dosage and time in male fish after being fed with a diet containing E2. In addition, the E2 contents in female ovaries showed a significant increase after 250 mg of E2/kg treatment for 14 d. On the other hand, the fecundity rate of F-E2 group was lower around 2 folds than FC (female fed 0 mg of E2/kg) group. Craniofacial chondrogenesis on 72 hpf (hours of post fertilization) of F-E2 larvae were abnormalities, and a recovery to a normal developmental pattern was observed at the 96 hpf stage. The swimming speed was slower for F-E2 larvae compared to the FC larvae; and the F-E2 juvenile seems to be less responsive to cortisol (LRC) after cold stress. According to the results, we suggested that F-E2 larvae might have worse environmental adaptability than FC larvae.

Effects of bisphenol A or diethyl phthalate on cartilage development and the swimming behavior of zebrafish (Danio rerio) through maternal exposure.

Waterborne bisphenol A (BPA) and diethyl phthalate (DEP) are endocrine disruptive chemicals that impact the reproductive system of fish. The present study checks the effectiveness of the reproductive capacity on zebrafish after BPA and DEP exposure, and consequently investigates its effect on their development and the swimming behavior of its offspring. The exposure of BPA and DEP to zebrafish reveals that the levels of ovarian 17ß-estradiol (E2) and relative mRNA expression (RRE) ratios (Treatment/Control) of hepatic vitellogenin (vtg1) could be induced and decreased. Liver RRE levels in estrogen receptors (ERs) are also affected. Among the ERs, esr2a significantly increased upon BPA exposure, and esr1 and esr2b decreased upon DEP exposure. In addition, the ceratohyal cartilage (CH) angle of larvae whose mothers were exposed to BPA (F-BPA) was significantly bigger, but the CH angle of larvae whose mothers were exposed to DEP (F-DEP) was significantly smaller than the control. The swimming performance of larvae from F-DEP was more compromised than the control, but the situation did not appear in the larvae from the F-BPA group. The success rate of larvae hatching from F-BPA and F-DEP was lower than control group. Moreover, the successful rate of female spawns was higher in the control group compared to the treatment groups exposed to BPA and DEP. We suggested that both maternal BPA and DEP disrupt E2 levels, and influence the CH development of larvae, resulting in a decrease in successful hatching. Only the swimming behavior of larvae from maternal DEP was disrupted.

Association between NAFLD and risk of prevalent chronic kidney disease: why there is a difference between east and west?

BACKGROUNDS: There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. METHODS: Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. RESULTS: A total of 60,965 participants were analyzed, including 11,844 from the US and 51,229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p < 0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. CONCLUSION: NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.

Changes in vitellogenin and estrogen receptor expression and 17ß-estradiol concentration in male juvenile tilapia can be used to evaluate endocrine-disrupting chemicals.

The effects of endocrine disruption with respect to potential human toxicities have been extensively evaluated to date. However, the standard testing methods used have not always taken the most pertinent approach. In this study, we used juvenile male tilapia (Oreochromis niloticus) as an animal model to test for endocrine disruption by chemicals. We measured 17ß-estradiol (E2) concentrations, and the mRNA relative expression ratio (RER; treatment/control) of vitellogenin (vtg2) and estrogen receptors (ERs) to assess whether the effluent concentration of selected plasticizers disrupt E2 function in fish. We found that the vtg2 RER was significantly increased after exposure to 2.52 nM E2 for 5 days, 0.438 µM of bisphenol A (BPA) for 7 days, or 2.865 µM Cd2+ for 7 days. These data support vtg2 transcript level as a sensitive biomarker to evaluate contamination of water by endocrine disrupting chemicals (EDCs). However, vtg2 expression did not respond to fluctuations of E2 concentrations in the tilapia juveniles exposed to selected plasticizers. However, the RER of three types of ERs appeared to change dramatically upon exposure to plasticizers. ERα significantly increased, but ERß2 decreased with 3.6 µM DEP exposure. Both ERα and ERß2 decreased significantly after 1.44 µM DIBP exposure. We suggest that changes of vtg2 mRNA RER, E2 levels and ERs mRNA expression should be taken into consideration at the same time to determine if chemical contaminants in the water are endocrine disrupters.

Effects of calcium and estrogen on the development of the ceratohyal cartilage in zebrafish (Danio rerio) larvae upon embryo and maternal cadmium exposure.

The present study is to investigate the reason why the ceratohyal cartilage (CH) angle of zebrafish larvae were larger compared to the control group after their female parents were treated with cadmium (F-Cd). However, the CH angle was smaller compared to the control group when embryos were directly exposed to Cd2+ for 72 h (D-Cd). Results showed that calcium contents of larvae were lower than the control, but the transporter isoforms trpv4 and trpv6 mRNA expressions were significantly increased upon D-Cd treatment. Furthermore, external Ca2+ added during D-Cd treatment reveals that the CH angles of larvae did not appear significantly different compared to the control. On the other hand, E2 (17ß-estradiol) contents were higher around 1.9 folds in the ovaries of females; CH angle were over 25°, and Cd2+ contents were higher around 6 folds than the control group on larvae treated through F-Cd treatment; CH angles and E2 levels on larvae were higher than the control after the larvae were treated with 1.84 µM E2 (D-E2); Estradiol receptor (ER) isoforms ERß1 and ERα mRNA expressions significantly increased when 0 hpf embryos were either treated with D-E2 or D-Cd. According to the results, we suggested that the CH angle of larvae become larger upon F-Cd treatment due to maternal Cd2+ inducing E2 levels. However, the CH angle of larvae appeared to be smaller compared to the control upon D-Cd treatment. We suggested that the CH angle decreased due to the decrease of Ca2+ contents upon Cd2+ exposure.

Anti-oxidative Responses on Hepatic Tissue of Zebrafish (Danio rerio) in a Short Duration of Sub-lethal Concentrations of Cadmium Exposure.

The aim of the present study was to identify whether the responses of oxidative stress in zebrafish liver are similar to those in mammalians upon low doses of Cd2+ exposure in short durations. Fish were exposed to 1.78 µM Cd2+ (treatment) and 0.0 µM Cd2+ (control) for 0, 1, 3, and 6 h. The reactive oxygen species (ROS) and lipid peroxidation (LPO) of hepatic tissues significantly increased after 3 and 6 h of Cd2+ exposure, respectively. Antioxidants glutathione peroxidase (gpx1a), superoxide dismutase (sod), and catalase (cat) were up regulated after 1-3 h, and metallothionein isoforms (smtB and mt2) increased after 3-6 h of Cd2+ exposure. The caspase-3 and p53 mRNA expressions significantly increased threefolds after 1 h of Cd2+ exposure. Results confirmed that oxidative stress in the hepatic tissue was induced by Cd2+ within 3 h. However, anti-oxidative functions immediately up regulated, causing cell apoptosis levels to decrease after 6 h of Cd2+ exposure.

Anti-oxidative functions of mt2 and smtB mRNA expression in the gills and brain of zebrafish (Danio rerio) upon cadmium exposure.

There were not any past studies about metallothionein isoforms (smtB and mt2) having anti-oxidative functions on zebrafish after Cd2+ exposure. On the other hand, the anti-oxidative enzymatic factors such as superoxide dismutase (sod), glutathione peroxidase (gpx1a), and catalase (cat) are used as references to investigate whether the smtB and mt2 have anti-oxidative responses on the gills and brain of zebrafish after 1-6 h of 0 and 1.78 µM Cd2+ exposure. The anti-oxidative system such as sod, cat, and gpx1a mRNA expressions demonstrated a cascade response upon Cd2+-induced oxidative stress in the present study. Interestingly, the smtB mRNA expression levels increased by 3.2- to 6.1-fold, and mt2 raised by 4.1- to 11.3-fold in gills at 1 and 3 h after exposure to Cd2+, respectively. On the other hand, the smtB mRNA levels increased by 10.6- to 58.6-fold, but mt2 mRNA levels increased by 2.3- to 11.1-fold in brain at 1 and 3 h after exposure to Cd2+, respectively. In addition, both tissues showed increased apoptosis levels at 3 h, and recovery after 6 h of Cd2+ exposure. From the results, we suggest that both mt2 and smtB play a role in anti-oxidation responses within 6 h after exposure to Cd2+. In conclusion, the smtB mRNA levels have a higher response than mt2 in the brain, but both mRNA expressions appear to have a similar pattern in the gill. We suggest that smtB plays an important role to defend oxidative stress in the brain of adult zebrafish upon acute Cd2+ exposure.

Anti-oxidative responses of zebrafish (Danio rerio) gill, liver and brain tissues upon acute cold shock.

The present study seeks to detect oxidative damage and to compare anti-oxidative responses among liver, gills and brain of adult zebrafish that were cooled from 28 °C (control) to 12 °C (treatment) for 0-24 h. The lipid peroxidation of liver, gill and brain tissues significantly increased at 1h after transfer, but reactive oxygen species in the treatment group increased significantly after 24 h as compared to the control. The fish were found to develop a cascading anti-oxidative mechanism beginning with an increase in Cu/Zn-SOD levels, followed by increased CAT and GPx mRNA expressions in the three tissue types. Both smtB and mt2 mRNAs increased in the hepatic and brain tissues following 1h of cold stress, but only smtB exhibited a significant increase in the gills at 1 h and 6 h after transfer to 12 °C. Furthermore, cellular apoptosis in the brain was not evident after cold shock, but liver and gills showed cellular apoptosis at 1-3 h, with another peak in the liver at 6 h after cold shock. The results suggest that the cold shock induced oxidative stress, and the enzymatic (SOD, GPx and CAT) and non-enzymatic (mt-2 and smt-B) mRNA expressions all play a role in the resulting anti-oxidation within 1-6 h of cold shock. A functional comparison showed that the brain had the most powerful antioxidant defense system of the three tissue types since it had the highest smtB mRNA expression and a lower level of cell apoptosis than the liver and gills after exposure to cold stress.

Analyzing the effectiveness of using branchial NKA activity as a biomarker for assessing waterborne copper toxicity in tilapia (Oreochromis mossambicus): A damage-based modeling approach.

Branchial Na(＋)-K(＋)-ATPase (NKA) activity has been suggested as a promising biomarker for assessing metal stress in aquatic organisms. However, studies that systematically show the effectiveness of using NKA activity to detect metal exposure and toxicity at the individual level are limited. In this study, we aimed to determine whether branchial NKA activity mechanistically responds to the accumulation of waterborne copper (Cu) and accounts for observed toxicity over time under environmentally-relevant and aquafarming Cu exposure levels (0.2, 1 and 2 mg L(-1)). Temporal trends in Cu accumulation and the corresponding responses of branchial NKA activity resulting from Cu exposure were investigated in laboratory experiments conducted on juvenile tilapia (Oreochromis mossambicus), a freshwater teleost that shows potential as a bioindicator of real-time and historical metal pollution. We used the process-based damage assessment model (DAM) to inspect the time course of Cu toxicity by integrating the compensation process between Cu-induced inhibition and repair of branchial NKA activity. NKA activity acted as a sensitive biomarker for Cu exposure and accumulation in tilapia, which showed induced impairment of osmoregulation and lethality when they were exposed to environmentally relevant levels (0.2 mg L(-1)), but not to higher exposure levels (1 and 2 mg L(-1)) in aquaculture farms or contaminated aquatic ecosystems. This study highlights the benefits and limitations of using branchial NKA activity as a sensitive biomarker to assess the health status of a fish population and its ecosystem.

Profiles of thyrotropin, thyroid hormones, follicular cells and type I deiodinase gene expression during ontogenetic development of tilapia larvae and juveniles.

The aims of the present study are to determine whether triiodothyronine (T3) and/or thyroxine (T4) in tilapia larvae is gifted through the mother, and to investigate the change profiles of thyrotropin (TSH), thyroid follicular cells and type I deiodinase (D1) gene expression following larval development. T3 and T4 contents were measured using radioimmunoassay, thyrotropin was observed using immunocytochemistry, and the D1 gene was cloned and measured using real-time PCR. Results indicated that the ß-TSH-immunoreactive cells (thyrotropin ICC) signals were detected at 9 dph (i.e., 9 days of post-hatching). Thyroid follicular cells were observed first at 3 dph, while the T3 contents of the whole body gradually decreased before 11 dph. T4 contents were detected until 13 dph, with higher secretion during 19-21 dph. In addition, the T3 synthesis was not inhibited by thiourea (TU) before 13 dph, but the TU response in the larvae appeared after 13 dph. Type I deiodinase (D1: GenBank accession number KC591724) was found to contain 2444 bases and encoded 248 amino acids. The D1 mRNA expression began to increase at 13 dph, with a higher expression during 15-19 dph. These results suggested that the T3 contents were maternally derived before 13 dph. Both thyroid hormonal changes and some parameters related to thyroid hormone synthesis in ontogenetic tilapia are discussed.

Magnetite nanoparticle-induced fluorescence quenching of adenosine triphosphate-BODIPY Conjugates: application to adenosine triphosphate and pyrophosphate sensing.

We report that magnetite nanoparticles (Fe3O4 NPs) act as an efficient quencher for boron dipyrromethene-conjugated adenosine 5'-triphosphate (BODIPY-ATP) that is highly fluorescent in bulk solution. BODIPY-ATP molecules attached to the surface of Fe3O4 NPs through the coordination between the triphosphate group of BODIPY-ATP and Fe(3+)/Fe(2+) on the NP surface. The formed complexes induced an apparent reduction in the BODIPY-ATP fluorescence resulting from an oxidative-photoinduced electron transfer (PET) from the BODIPY-ATP excited state to an unfilled d shell of Fe(3+)/Fe(2+) on the NP surface. A comparison of the Stern-Volmer quenching constant between Fe(3+) and Fe(2+) suggests that Fe(3+) on the NP surface dominantly controls this quenching process. The efficiency for Fe3O4 NP-induced fluorescence quenching of the BODIPY-ATP was enhanced by increasing the concentration of Fe3O4 NPs and lowering the pH of the solution to below 6.0. We found that pyrophosphate and ATP compete with BODIPY-ATP for binding to Fe3O4 NPs. Thus, we amplified BODIPY-ATP fluorescence in the presence of increasing the pyrophosphate and ATP concentration; the detection limits at a signal-to-noise ratio of 3 for pyrophosphate and ATP were determined to be 7 and 30 nM, respectively. The Fe3O4 NP-based competitive binding assay detected ATP and pyrophosphate in only 5 min. The selectivity of this assay for ATP over metal ions, amino acids, and adenosine analogues is particularly high. The practicality of using the developed method to determine ATP in a single drop of blood is also validated.

Effects of maternal cadmium exposure on female reproductive functions, gamete quality, and offspring development in zebrafish (Danio rerio).

Impacts of maternal Cd(2+) exposure on female zebrafish (Danio rerio) were observed in females as well as their offspring. In females, Cd disturbed fecundity and other reproductive functions. In their offspring, it retarded gamete development and growth and influenced gene expression. There was a positive relationship between Cd(2+) contents in ovaries of females and treatment doses of 0-8.9 µM of Cd(2+). The mating rate decreased by 60 % when females were exposed to 8.9-35.6 µM of Cd(2+) for 72 h compared with the control group. It was observed that growth is delayed by one somite stage in maternal-Cd(2+) embryos compared with control embryos, which grew at the sixth-somite stage. The ceratohyal angles of larvae of Cd-exposed adults (maternal Cd(2+)) at 72 h postfertilization (hpf) appeared to have a positive response after doses of maternal Cd. In addition, approximately 30 % of 96-hpf larvae that were treated with a dose of 35.6 µM of maternal Cd(2+) appeared to have pericardial edema. At the 5-hpf stage of maternal Cd(2+) exposure, embryos showed 33 and 37 target genes, respectively, that were significantly downregulated and upregulated as shown by cDNA microarray analysis. A major effect of maternal Cd(2+) exposure on zebrafish embryo genes is that 18.9% of transcription functions were upregulated. In addition, 33.3% of transcripts relative to the function of protein biosynthesis were downregulated. These results showed that maternal Cd(2+) exposure influenced the reproduction ability of females and also caused their embryos to develop with abnormal gene expression.

Maternal cadmium exposure induces mt2 and smtB mRNA expression in zebrafish (Danio rerio) females and their offspring.

The present study aimed to identify the effects of maternal cadmium (Cd(2+)) exposure on the mRNA expression of mt2 (metallothionein-2) and smtB (similar to metallothionein-B) in female zebrafish (Danio rerio) and their offspring (F1 larvae). Zebrafish females were exposed to 0, 8.9, 17.8, and 35.6 µM Cd(2+) for 72 h, and their ovaries and F1 larvae were collected to measure their Cd(2+) contents and their smtB and mt2 mRNA expression. Cd(2+) contents and the mRNA expression of smtB and mt2 in F1 larvae all showed positive correlations with the maternal Cd(2+) treatment dose. The mt2 was 1.9- to 3.4-fold higher than smtB in F1 larvae. Furthermore, F1 larvae had noticeably enhanced Cd(2+) tolerance after maternal Cd(2+) treatment. These results demonstrate that maternal Cd(2+) was transferred to larval fish and induced mt2 and smtB mRNA expression to protect larva against the impacts of Cd(2+). In female ovaries, mt2 expression showed a noticeable increase after exposure to a metal environment, while smtB did not show exactly the same effect. The study can only conclude that smtB might have a much different role other than just protecting against the impacts of metals.

Effects of ambient cadmium with calcium on mRNA expressions of calcium uptake related transporters in zebrafish (Danio rerio) larvae.

The mRNA expression levels of Ca²âº transporter genes including the epithelial calcium channel (ECaC), sodium/calcium exchanger 1b (NCX1b), and plasma membrane calcium ATPase 2 (PMCA2) were measured in zebrafish larvae after exposure to 0.08 µM Cd²âº in either water mixed with 0.2 mM Ca²âº (lCa) or 2 mM Ca²âº (hCa). The ECaC and NCX1b expression decreased at the 48 and 72 h mark, respectively; however, PMCA2 transcripts decreased at 96 h after exposure to Cd²âº in lCa environment. On the other hand, the ECaC transcripts were not affected; however, the PMCA2 transcripts were increased at 72 h, while the NCX1b transcripts significantly decreased at 48 and 96 h after exposure to Cd²âº in a hCa environment. The Ca²âº contents of larvae significantly decreased after Cd²âº exposure in a lCa environment; however, the Ca²âº contents were evidently higher after exposure to Cd²âº in a hCa environment, except for 48th h mark. In addition, ECaC morphants showed lower Ca²âº contents of whole-body, and there were higher levels of mortality after exposure to the same condition compared to the wild-type groups. In contrast, injection of ECaC cRNA resulted in an increase in Ca²âº content and the rate of Ca²âº influx in zebrafish embryos. Summary, the results showed that the Ca²âº transporters of zebrafish larvae were impacted after exposures of 0.08 µM Cd. However, in the exposure condition, the ECaC and PMCA2 transcripts could be restored to control levels after the fish were treated in an environment with hCa.

Changes of glycogen metabolism in the gills and hepatic tissue of tilapia (Oreochromis mossambicus) during short-term Cd exposure.

The aim of the study was to test the hypothesis that the mechanism of glycogen metabolism has taken place in gills rather than in liver during Cd exposure. Male tilapia were exposed to 44.45 µM ambient Cd for 12h, and we found blood glucose significantly increased, however, lactate levels showed no significant changes. The glycogen phosphorylase (GP) activity increased immediately after 0.75 to 3h of Cd exposure in the gills, and after 1 to 6h in the liver, respectively. In addition, the glycogen level depleted faster in the gills than in the liver. Plasma cortisol level increased from 0.25 to 1h and recovered after 3h, while the glucagon did not significantly change during Cd exposure. Glucocorticoid receptor (GR) mRNA expression decreased after 0.75 h in the gills, while it significantly increased after 6h in the liver. Ca(2+), Na(+), Cl(-), and K(+) significantly decreased upon Cd exposure within 6h following Cd-induced toxic stress. We suggested that the cortisol is the spontaneous stimulation of glycogen metabolism in the gills, and it triggers a subsequent energy supply later in the liver. Taken together, the profile of glycogen metabolism between gills and liver during Cd-exposure stress provide good support to our hypothesis.

Spirulina prevents memory dysfunction, reduces oxidative stress damage and augments antioxidant activity in senescence-accelerated mice.

Spirulina has proven to be effective in treating certain cancers, hyperlipidemia, immunodeficiency, and inflammatory processes. In this study, we aimed to investigate the effects of Spirulina on memory dysfunction, oxidative stress damage and antioxidant enzyme activity. Three-month-old male senescence-accelerated prone-8 (SAMP8) mice were randomly assigned to either a control group or to one of two experimental groups (one receiving daily dietary supplementation with 50 mg/kg BW and one with 200 mg/kg BW of Spirulina platensis water extract). Senescence-accelerated-resistant (SAMR1) mice were used as the external control. Results showed that the Spirulina-treated groups had better passive and avoidance scores than the control group. The amyloid ß-protein (Aß) deposition was significantly reduced at the hippocampus and whole brain in both Spirulina groups. The levels of lipid peroxidation were significantly reduced at the hippocampus, striatum, and cortex in both Spirulina groups, while catalase activity was significantly higher only in the 200 mg/kg BW Spirulina group than in the control group. Glutathione peroxidase activity was significantly higher only in the cortex of the 200 mg/kg group than in that of the SAMP8 control group. However, superoxide dismutase activity in all parts of the brain did not significantly differ among all groups. In conclusion, Spirulina platensis may prevent the loss of memory possibly by lessening Aß protein accumulation, reducing oxidative damage and mainly augmenting the catalase activity.

Cadmium concentration and metallothionein expression in prostate cancer and benign prostatic hyperplasia of humans.

BACKGROUND/PURPOSE: Cadmium (Cd) causes various genitourinary disorders and is a carcinogen for prostate cancer. Metallothionein (MT) is a protein that detoxifies heavy metals. We evaluated changes in Cd concentration and MT expression in human prostate cancer (CaP) and benign prostatic hyperplasia (BPH). Our goal was to clarify the relationship between Cd concentration and MT expression in prostatic diseases. METHODS: The experimental group consisted of 18 patients who underwent radical prostatectomy for CaP. The control group consisted of 35 patients who underwent transurethral resection of the prostate for BPH. Tissue samples were acquired from the gross tumor site and from resected chips. We determined Cd concentration by atomic absorption, MT expression by immunoblotting, and immunohistochemical staining. The significance of between-group differences for these outcomes was analyzed using Student's t tests. RESULTS: There was no statistically significant difference in Cd concentration between the CaP and BPH groups. Immunoblots from both groups revealed a single band. The relative intensity of the MT band was 0.58 +/- 0.09 in the BPH group and 0.17 +/- 0.03 in the CaP group. MT expression in patients with BPH was 3.4-fold higher than in those with CaP. CONCLUSION: MT may bind heavy metals and protect patients from CaP. Additional studies are needed to reveal the factors that influence the expression of MT in prostate epithelial cells, and to analyze the free and compound forms of Cd at the same time.