Investigation of the toxicity of common oxidants used in advanced oxidation processes and their quenching agents.

The inhibitory effect of commonly known oxidants and their quenching agents was investigated by employing a battery of toxicity tests. Hydrogen peroxide toxicity could be effectively eliminated by the enzyme catalase, whereas sodium thiosulfate and ascorbic acid were recommended as suitable quenching agents for the removal of the oxidants persulfate and peroxymonosulfate in the Vibrio fischeri bioassays. None of the studied quenching agents was found to be suitable for persulfate and peroxymonosulfate in the Daphnia magna bioassays since high inhibitory effects were obtained for both oxidants. In the case of Pseudokirchneriella subcapitata, manganese dioxide powder should be used as an alternative quenching agent to catalase, since this enzyme exhibited a highly toxic effect towards these microalgae. Sodium sulfite, which is extensively used as a quenching agent, was not appropriate for quenching peroxymonosulfate in all studied bioassays.

Mutagenicity and cytotoxicity of liquid waste, press water and pond water, produced in the cassava flour industry, and of antitoxic sodium thiosulfate.

BACKGROUND: Cassava (Manihot esculenta Crantz), a plant used as food and an ingredient in industry, contains cyanogenic glycosides. The cassava root contains wastewater, popularly known as manipueira, which is a toxic substance. Its ingestion by animals causes poisoning although they react positively to treatment with sodium thiosulfate. The present research evaluates the cytotoxicity and the mutagenicity of liquid waste produced in the process of industrialization of the bitter cassava, olho-junto variety. The liquid wastes are characterized as press water, which is obtained when the cassava roots are pressed; pond water, which is press water stored in impounded ponds; and a solution of sodium thiosulfate, pure and with other waste. RESULTS: The system tests comprised root meristematic cells of Allium cepa L. and bone marrow cells of Rattus norvegicus. Treatment with saline solution was cytotoxic for Allium cepa L. and significantly reduced cell division rate. Although no treatment was cytotoxic in any of the tests with rats, the thiosulfate solution was clastogenic for the chromosomal aberrations test. CONCLUSION: Since it is harmful to the genetic material submitted within the conditions of current research, sodium thiosulfate should only be used in emergency conditions in which the benefits exceed the risks.

Lethal doses of oxbile, peptones and thiosulfate-citrate-bile-sucrose agar (TCBS) for Acanthaster planci; exploring alternative population control options.

Effective control of outbreaks of Acanthaster planci represents the most immediate and practical intervention to reverse sustained declines in coral cover on reefs in the Indo-Pacific. This study explored the minimum doses of oxbile, oxgall, and thiosulfate-citrate-bile-sucrose agar (TCBS) that result in reliable and comprehensive mortality when injected into adult A. planci. The minimum doses required to induce 100% mortality among starfish (n=10) were 4 g l(-1) of oxbile, 8 g l(-1) of oxgall and 22 g l(-1) of TCBS. Moreover, there was no evidence of unintended side effects for other coral reef organisms (e.g., scleractinian corals, echinoderms and fishes) when using oxbile, oxgall, or TCBS at minimum doses. The effectiveness of peptones in killing crown-of-thorns starfish was also tested, but inconsistency in the results revealed that these proteins are unreliable.

Fatal and non-fatal cases of lime sulfide exposure and pathogenetic mechanisms underlying pancreatic injury: Case reports with an animal experiment.

Lime sulfide poisoning by the oral route is rarely encountered in the practice of forensic science, whereas hydrogen sulfide poisoning is seen frequently. We report here two cases of fatal lime sulfide poisoning with several related cases and in addition induced histological damage with acute inflammation in animal models under at similar concentrations. We also evaluated sulfide and thiosulfate concentrations and speculated as to the cause of pancreatic damage in these cases.

The effect of sodium thiosulfate on the metabolism of cis-platin in human plasma in vitro.

The anticancer drug cis-platin (CP) is widely used to treat patients, but it is also associated with significant side effects, including nephrotoxicity. Given that this metallodrug is intravenously (iv) administered, its biotransformations in the bloodstream are likely to be involved in mediating these side-effects. Previous studies have revealed that the iv administration of patients/mammalian model organisms with sodium thiosulfate (STS) can ameliorate the side effects of CP, but the underlying molecular basis remains elusive. We have studied the effect of STS on the metabolism of CP in human plasma in vitro by determining the platinum (Pt) distribution using size exclusion chromatography (SEC) coupled on-line to an inductively coupled plasma atomic emission spectrometer (ICP-AES). The addition of STS to plasma 10 min before CP was added accelerated the hydrolysis of CP and resulted in the formation of a Pt-STS complex. Conversely, when plasma was incubated with CP for up to 3 h and STS was added thereafter the analysis of the obtained mixture revealed that the formation of the same Pt-STS complex which in turn greatly diminished the plasma protein binding of CP-derived hydrolysis products. Thus, the observed amelioration of the side effects of CP by STS can be rationalized in terms of the rapid formation of a biologically inactive Pt-STS complex in the bloodstream. This is the first mechanism that can explain the amelioration of the side effects of CP by STS. Based on the fact that cis-platin remained in plasma for a considerable amount of time, the optimization of the administration sequence, the molar ratio and the time delay between the administration of both drugs emerges as a viable strategy to achieve a careful balance between ameliorating the side effects while leaving the antitumour activity intact. Our results demonstrate that in vitro studies can be useful to develop feasible strategies to mitigate the side-effects of Pt-based anticancer drugs in patients.

Dinitrosyl iron complexes with thiol-containing ligands and apoptosis: studies with HeLa cell cultures.

No pro-apoptotic effect of dinitrosyl iron complexes (DNIC) with glutathione, cysteine or thiosulfate was established after incubation of HeLa cells in Eagle's medium. However, DNIC with thiosulfate manifested pro-apoptotic activity during incubation of HeLa cells in Versene's solution supplemented with ethylene diamine tetraacetate (EDTA) known to induce the decomposition of these DNIC. The water-soluble о-phenanthroline derivative bathophenanthroline disulfonate (BPDS) had a similar effect on DNIC with glutathione during incubation of HeLa cells in Eagle's medium. It was assumed that EDTA- or BPDS-induced pro-apoptotic effect of DNIC with thiosulfate or glutathione is coupled with the ability of decomposing DNIC to initiate S-nitrosylation of proteins localized on the surface of HeLa cells. Presumably, the pro-apoptotic effect of S-nitrosoglutathione (GS-NO) on HeLa cells preincubated in Eagle's medium is mediated by the same mechanism, although the pro-apoptotic effect based on the ability of GS-NO to initiate the release of significant amounts of NO and its oxidation to cytotoxic peroxynitrite in a reaction with superoxide should not be ruled out either. No apoptotic activity was found in the presence of bivalent iron and glutathione favoring the conversion of GS-NO into DNIC with glutathione. It is suggested that interaction of HeLa cells with intact DNIC with glutathione or thiosulfate results in the formation of DNIC bound to cell surface proteins.

Sodium thiosulfate exposure disrupts in vitro and in vivo heart development.

It is well-known that the majority of malformations found in the human population is based on complex gene-environment interactions. As an industrial chemical sodium thiosulfate (STS) is used heavily in many industries. Nevertheless, there is little known about the effects of STS on embryo development. In the present study, we have investigated the effects of STS on cardiac development in rat cardiomyocyte H9C2 cell line and chick embryos. As determined by MTT assays, the proliferation of H9C2 cells was inhibited by STS in a dose-dependent manner. Fertilized eggs injected via the yolk sac with STS at Hamburger-Hamilton (HH) stages 6, 9 and 12 showed significantly increased cardiotoxicity at HH stage 18, including cardiomyocyte apoptosis and animal mortality. Western blot analysis showed that STS significantly affected the expression of the apoptosis-related genes bcl-2, bax, and caspase-3 in a dose-dependent manner in the H9C2 cell line and in chick embryos. Dysregulation of apoptosis was correlated with embryonic heart malformations. Thus, STS may be a potent cardiac teratogen during embryo development.

Effect of Azadirachta indica (neem), sodium thiosulphate and calcium chloride on changes in nitrogen transformations and inhibition of nitrification in soil incubated under laboratory conditions.

A laboratory experiment was conducted to examine the effects of nitrification inhibitors (NIs) neem seed-cake (Azadirachta indica) (NSC), sodium thiosulphate (Na2S2O3) and calcium chloride (CaCl2) on changes in NH4(+)⁻N, inhibition of nitrification and recovery of applied nitrogen (N) in soil. Surface soil samples of 0-15 cm were collected from an arable field, amended with urea N (UN) at the rate 200 mg N kg⁻¹, UN+NSC, UN+Na2S2O3 and UN+CaCl2 and incubated at 22°C periodically over 50 d. Soil without any amendment was used as check (control). Results indicated that more than 58% of N applied as NH4⁻ disappeared over a period of 50 d from the soil mineral-N pool. Some of this N (21%) was accumulated as NO3⁻-N while the remaining N was unaccounted for. Addition of nitrification inhibitors NSC, Na2S2O3, and CaCl2 resulted in a decrease in the extent of NH4(+) disappearance by 35%, 44% and 30%, respectively. In the treatment receiving UN alone, 56 mg NO3⁻-N kg⁻¹ was accumulated over 50 d (maximum 93 mg kg⁻¹) indicated an active nitrification. Application of nitrification inhibitors NSC, Na2S2O3, and CaCl2 with UN inhibited nitrification by 54%, 64%, and 59%, respectively. Apparent N recovery (ANR) in the treatment receiving UN alone was 63% that substantially increased to 83%, 89% and 76% in the treatments receiving UN+NSC, UN+Na2S2O3, and UN+CaCl2, respectively indicating 32%, 41% and 20% increase in N recovery. Among three NIs tested, Na2S2O3 proved superior in inhibiting nitrification and increasing ANR. The study demonstrated that application of NSC, Na2S2O3, and CaCl2 which are cheap and easily available NIs inhibited nitrification and improved N recovery efficiency of applied N in an arable soil very effectively. It is suggested that these inhibitors should be tested under field conditions for increasing NUE and improving crop productivity.

Teratogenic effects of sodium thiosulfate on developing zebrafish embryos.

Sulfuric derivatives are potentially hazardous to human health, especially during embryogenesis. Zebrafish were used to study the toxic effect of sodium thiosulfate (STS) (1~1 x 10(-6) mol/L) on embryo development with real-time in vivo imaging. Motor neuron differentiation and proliferation were analyzed by detecting the dynamics of acetylated tubulin (alpha-tubulin) and of proliferating cell nuclear antigen (PCNA). The expression pattern of brain- and muscle-specific microRNAs was detected by whole-mount in situ hybridization. The development of embryos exposed to 0.1~1 mol/L STS was severely retarded and was accompanied by malformation of multiple organs; embryos exposed to 10 micromol/L~10 mmol/L STS had circulatory, nervous and maxillofacial malformations. Embryos were more sensitive to STS at 48 hours post fertilization (hpf) compared with 24 and 96 hpf. STS can destroy the normal development of motor neurons and can affect cell proliferation. We also found differential expression of miR-124a and miR-133a in STS-treated embryos. STS interferes with the normal cytoskeleton structure, inhibits cell proliferation and leads to nervous, cardiac and maxillofacial malformations. MiR-124a and miR-133a were involved in STS malformation induction.

Comparison of effects of epigallocatechin-3-gallate on hypoxia injury to human umbilical vein, RF/6A, and ECV304 cells induced by Na(2)S(2)O(4).

Hypoxia is related to the etiology of numerous pathological disease states, such as the formation of tumors or diverse retinopathies. Epigallocatechin-3-gallate (EGCG), a potent polyphenolic antioxidant and antiangiogenic compound found in green tea, has been shown to suppress the growth of blood vessels necessary for the growth of tumors and the induction of retinopathies. However, only a few studies have been carried focusing on the protective effects of EGCG on hypoxia-induced injury of cultured endothelial cells. The present study investigated the effects of EGCG on Na(2)S(2)O(4)-induced hypoxic injury in three types of cultured endothelial cells, primary isolates of normal human umbilical vein endothelial cells (HUVECs), and two transformed endothelial cells lines, RF/6A and ECV304. Our results indicated that Na(2)S(2)O(4) inhibited the growth of HUVE, RF/6A, and ECV304 cells in a dose-dependent manner; EGCG also exerted inhibitory effects on the growth of the three cell types, but the toxicity of EGCG to HUVECs was less than to RF/6A and ECV304 cells. The viability of HUVE, RF/6A, and ECV304 cells treated with EGGC were the lowest at 24, 24, and 36 h, respectively, and the IC(50) of EGCG were 420 +/- 8.0, 125 +/- 7.1, and 75 +/- 5.1 microM, respectively. Furthermore, EGCG, an efficient nontoxic agent, protected all three cell types from Na(2)S(2)O(4)-induced hypoxia injury, providing partial protection from hypoxia-induced injury in normal endothelial cells at 100, 30, and 10 microM for HUVE, RF/6A, and ECV304 cells, respectively.

Kinetics of Cisplatin and its monohydrated complex with sulfur-containing compounds designed for local otoprotective administration.

The anticancer drug cisplatin can cause permanent inner ear damage. We have determined the second-order degradation rate constant, k(Nu), of cisplatin and its more toxic monohydrated complex (MHC) in the presence of each of the sulfur-containing nucleophiles N-acetyl-l-cysteine, l-cysteine methyl ester, 1,3-dimethyl-2-thiourea, d-methionine, and thiosulfate, compounds that are under evaluation for local administration to prevent cisplatin-induced ototoxicity. MHC was isolated from a hydrolysis solution of cisplatin using liquid chromatography (LC). The degradations were evaluated by measuring the disappearance of MHC and cisplatin at 37 degrees C and pH 7.4 in the presence of each of the nucleophiles using LC and photometric detection. The k(Nu) of MHC and of cisplatin was 0.044 M(-1)sec(-1) and 0.012 M(-1)sec(-1) with N-acetyl-l-cysteine, 0.24 M(-1)sec(-1) and 0.067 M(-1)sec(-1) with l-cysteine methyl ester, 0.16 M(-1)sec(-1) and 0.074 M(-1)sec(-1) with 1,3-dimethyl-2-thiourea, 0.070 M(-1)sec(-1) and 0.069 M(-1)sec(-1) with d-methionine, and 3.9 M(-1)sec(-1) and 0.091 M(-1)sec(-1) with thiosulfate, respectively. Our results suggest that thiosulfate, as being the strongest nucleophile, is a promising candidate for local application in order to reduce the inner ear content of MHC and cisplatin. However, otoprotection is a multifactorial event, and it remains to be established how important nucleophilicity is for the effectiveness of the protecting agent.

Precipitation of silver-thiosulfate complex and immobilization of silver by Cupriavidus metallidurans CH34.

Cupriavidus metallidurans CH34 is a facultative chemolithotrophic bacterium that possesses two megaplasmids (pMOL28 and pMOL30) that confer resistance to eleven metals. The ability of Cupriavidus metallidurans CH34 to resist silver is described here. Electronic microscopy, energy-dispersive X-ray (EDX) and X-ray diffractometry (DRX) observations revealed that C. metallidurans CH34 strongly associated silver with the outer membrane, under chloride chemical form. Using derivate strains of C. metallidurans CH34, which carried only one or no megaplasmid, we show that this resistance seems to be carried by pMOL30.

Application of toxicity identification evaluation procedures for characterizing produced water using the tropical mysid, Metamysidopsis insularis.

Toxicity identification evaluations (TIEs) were performed on seven produced water (PW) effluents from inland discharge facilities operated in Trinidad and Tobago, a Caribbean tropical country with one of the oldest commercial oil industries in the world. The research was performed to determine the presence and magnitude of toxicity and characterize which toxicants are responsible for observed effects. Marine effluent toxicity characterizations with Metamysidopsis insularis revealed high whole acute toxic-unit response for produced water ranged from 8.1 to > 17.0 acute toxic-unit (initial toxicity test) and 5.7 to 1,111 acute toxic-unit (baseline toxicity test). Toxicity test results for all sites except one, which had the highest toxicity, are comparative with similar studies on produced water. The toxicological causality of this complex mixture differed for each PW with nonpolar organics being consistently toxic in all samples. Other potential toxicants contributing to overall toxicity to a much lesser extent were metals, ammonia, and volatile organic compounds. With the use of sodium thiosulfate and filtration manipulations for only PW6 sample, there was very slight reduction in toxicity; therefore, oxidants and filterable materials were not a great contributing factor. Whole effluent toxicity also can be attributed to ionic imbalance and the very stable oil-in-water emulsion that consists of fine oil droplets (less than 0.1-10 microm with an average diameter of 2.5 microm). This investigation is the first of its type in Trinidad and demonstrates clearly the applicability of this test method and local test species for evaluating complex effluents in tropical environments.

The physiological effects of a biologically incorporated silver diet on rainbow trout (Oncorhynchus mykiss).

Silver was biologically incorporated into a diet by exposing rainbow trout for 7 days to 100 mg/l of waterborne silver as silver thiosulphate. These fish were processed into a fine powder (trout meal) and pelleted to form a nutritionally balanced feed which was then fed to juvenile rainbow trout (Oncorhynchus mykiss). Fish were fed either a diet containing 3.1 microg/g biologically incorporated silver (an environmentally relevant concentration), or one of three control diets containing approximately 0.05 microg/g Ag for 128 days. All dietary treatments were fed to satiation once daily. Dietary silver did not significantly affect mortality, growth, food consumption, or food conversion efficiency. Furthermore, ion regulation (plasma Na(+) levels and Na(+) influx rates), hematological parameters (hematocrit, plasma protein, hemoglobin levels), plasma glucose, metabolism (oxygen consumption, ammonia and urea excretion rates) and intestinal Na/K-ATPase and amylase activities were all unaffected. Based on the physiological parameters investigated here, this dietary silver exposure appeared to be physiologically benign to rainbow trout. However, silver concentrations in the livers of the silver-fed fish were significantly elevated at day 16, and reached a steady-state level of approximately 20 microg/g Ag by day 36. The concentration specific accumulation rate in the livers of fish fed biologically incorporated silver was about 4.6 orders of magnitude greater than when fed dietary silver sulfide, indicating much greater bioavailability. Despite this increase, hepatic metallothionein concentrations remained unchanged, in contrast to waterborne exposures, indicating that bioaccumulated silver behaves differently depending on whether it is taken up from the diet or from the water. Apart from a significant reduction in hepatic Cu at day 16, liver concentrations of Cu and Zn were not affected by dietary silver. Silver concentrations were also significantly elevated (relative to control fish) in the kidneys of the silver-treated fish on days 88 and 126, and in the gills and plasma at day 126.

Isomeric effects on thiosulfate transformation and detoxification of 1,3-dichloropropene.

The fumigant 1,3-dichloropropene (1,3-D) is one of the most heavily used pesticides but also a suspected carcinogen. Previous research has shown that 1,3-D was rapidly transformed and detoxified by ammonium thiosulfate (ATS), a sulfur and nitrogen fertilizer. As common formulations contain cis and trans isomers at roughly equivalent ratios, this study was conducted to understand isomeric differences in thiosulfate transformation and detoxification of 1,3-D. Under the same conditions, reaction of cis-1,3-D with thiosulfate was more than three times faster than trans-1,3-D, which was correlated with a lower reaction activation energy for the cis isomer. The trans isomer was considerably more toxic to the luminescent bacteria Vibrio fisheri than the cis isomer, but the toxicity was reduced by 14 times after thiosulfate transformation. Mutagenic activity to strains of Salmonella typhimurium was observed for trans-1,3-D but was not detected after thiosulfate transformation. These results suggest that thiosulfate transformation detoxifies 1,3-D primarily by deactivating the trans isomer, and the reaction is toxicologically beneficial, as it negates the potential harmful effects of 1,3-D to the environment and human health.

Reduced glutathione accelerates the oxidative damage produced by sodium n-propylthiosulfate, one of the causative agents of onion-induced hemolytic anemia in dogs.

The oxidative effects of sodium n-propylthiosulfate, one of the causative agents of onion-induced hemolytic anemia in dogs, were investigated in vitro using three types of canine erythrocytes, which are differentiated by the concentration of reduced glutathione and the composition of intracellular cations. After incubation with sodium n-propylthiosulfate, the methemoglobin concentration and Heinz body count in all three types of erythrocytes increased and a decrease in the erythrocyte reduced glutathione concentration was then observed. The erythrocytes containing high concentrations of potassium and reduced glutathione (approximately five times the normal values) were more susceptible to oxidative damage by sodium n-propylthiosulfate than were the normal canine erythrocytes. The susceptibility of the erythrocytes containing high potassium and normal reduced glutathione concentrations was intermediate between those of erythrocytes containing high concentrations of potassium and reduced glutathione and normal canine erythrocytes. In addition, the depletion of erythrocyte reduced glutathione by 1-chloro-2, 4-dinitrobenzene resulted in a marked decrease in the oxidative injury induced by sodium n-propylthiosulfate in erythrocytes containing high concentrations of potassium and reduced glutathione. The generation of superoxide in erythrocytes containing high concentrations of potassium and reduced glutathione was 4.1 times higher than that in normal canine erythrocytes when the cells were incubated with sodium n-propylthiosulfate. These observations indicate that erythrocyte reduced glutathione, which is known as an antioxidant, accelerates the oxidative damage produced by sodium n-propylthiosulfate.

Partitioning and effects of silver in amended freshwater sediments.

Sediments that represented a wide range of characteristics were amended with silver compounds to observe partitioning and bioavailability. In laboratory studies, silver partitioning to particulates, sediment pore water, and overlying water was measured and bioavailability of silver was determined using Hyalella azteca in 10-day sediment toxicity tests. Three silver compounds were used as sources of silver for this study: silver nitrate, silver chloride, and silver thiosulfate complex. Sediment amendment procedures were adjusted as necessary depending on the characteristics of the individual compounds. Several sediment characteristics such as organic carbon, pH, redox, and acid volatile sulfides regulated silver partitioning and bioavailability. Bioavailability of silver was correlated with the overlying water concentration of silver. Ten-day LC50 values ranged from 1.62 to 379.7 mg Ag/kg for H. azteca exposed to sediments amended with AgNO3. In laboratory experiments, silver chloride and silver thiosulfate were orders of magnitude less toxic and bioavailable than silver nitrate, with 10-day LC50 values greater than the highest concentrations of AgCl and silver thiosulfate complex amended to sediments (2560 and 1125 mg Ag/kg, respectively.

Increased therapeutic effect on metastatic liver tumors in rats of two-route chemotherapy using cis-diamminedichloroplatinum (II) and its antidote, sodium thiosulfate, with temporary clamping of the abdominal aorta.

To improve the therapeutic effects of conventional "two-route chemotherapy" (TRC) comprising cis-diamminedichloroplatinum(II) (CDDP) given via the hepatic artery plus simultaneous i.v. sodium thiosulfate (STS) on metastatic liver tumors in rats, we combined TRC with aortic clamping at the supraceliac level. Treatments were evaluated in Wistar-King-Aptekman (WKA) rats bearing metastatic liver tumors 7 days after the inoculation of 10(6) syngenic RBT-1 (transitional-cell carcinoma) cells via the mesenteric vein. When 15 mg/kg CDDP was injected i.a. over 5 min, immediately followed by STS 1,580 mg/kg (200-fold the molar equivalent of 15 mg/kg CDDP) given i.v. over a further 5 min, the antitumor activity, evaluated by the number of tumor nodules present 12 days after treatment, was superior to that of conventional TRC (15 mg/kg i.a. CDDP plus simultaneous administration of 1,580 mg/kg i.v. STS), but the blood urea nitrogen (BUN) level was highly elevated (63.6 mg/dl). With aortic clamping for 7.5 min during CDDP administration and the first half of STS treatment, the TRC consisting of CDDP plus delayed STS (modified TRC) exhibited a further improvement in antitumor activity, with no nephrotoxicity (BUN, 17.1 mg/dl). Although the antitumor activity of 3 or 5 mg/kg i.a. CDDP was also increased by aortic clamping, in animals with normal BUN levels the survival of those treated with modified TRC was greater than that of rodents given 3 mg/kg i.a. CDDP with aortic clamping; however, the former was the same as that of animals given 5 mg/kg i.a. CDDP with aortic clamping whose BUN levels were elevated (31.2 mg/dl). Loss of body weight, the decrease in WBC counts, and changes in the serum transaminase levels in rats given modified TRC were tolerable. The improved therapeutic effect of modified TRC can be explained as follows: during aortic clamping, (a) CDDP delivery to the kidney decreased by 96% and made feasible the delay in STS administration after CDDP without nephrotoxicity, and (b) CDDP retention in the liver was increased by 366%, as aortic clamping decreased the portal blood flow, thereby inhibiting the washout of CDDP from the liver.