Diquat Toxicity Research Articles

Association between toxicity-index of diquat and in-hospital mortality in patients with acute diquat poisoning: a retrospective cohort study

Background This study investigates the impact of diquat toxicity levels on in-hospital mortality rates among patients with acute diquat poisoning. It aims to clarify the relationship between diquat toxicity scores and the likelihood of death during hospitalization. Methods A retrospective cohort study was conducted on 98 individuals with acute diquat poisoning. Data on post-ingestion time, initial diquat plasma concentration, and clinical outcomes were systematically collected for all participants. The toxicity-index of diquat was calculated based on post-ingestion time and initial diquat plasma concentration. Logistic regression analysis was utilized to assess the association between the toxicity-index of diquat and in-hospital mortality rates, adjusting for potential confounding variables such as age, comorbidities, and treatment interventions. Results The study found that the overall prevalence of in-hospital mortality was 34.7%, with 58.2% in males. The multivariable-adjusted regression coefficient for in-hospital mortality associated with the toxicity-index was 1.09, with a 95% confidence interval (CI) of 1.01–1.17. Subsequent exploratory subgroup analysis indicated that there were no significant interactions (all p values for interaction were >0.05). Conclusions The study found that higher diquat toxicity-index values correlate with increased in-hospital mortality in acute diquat poisoning cases, indicating that the toxicity-index could be a useful biomarker for assessing mortality risk.

Toxicity of Diuron, Diquat and Terbutryn to Cyanobacterial Mats

This study investigated acute toxicity of Diuron, Diquat and Terbutryn to cyanobacterial mats collected from Wadi Gaza, Palestine. Toxicity was measured by the reduction of population growth of cyanobacterial mats exposed to various herbicide concentrations in the range of 0-15.44 μmole L-1. Optical density of cyanobacterial suspension was recorded using a spectrophotometer at 680 nm from time zero up to 8 days and taken as an indicator of growth. EC50 and ET50 values were estimated using linear regression equations. Results showed that cyanobacterial mats adapted and grew fast under laboratory conditions. The toxicity of Diuron, Terbutryn and Diquat reached 89.35, 76.02 and 71.24%, respectively. Toxicity of binary mixtures (Diuron and Diquat) decreased from 77.35% to 65.33% due to the reduction of Diuron concentration in the mixture. EC50 values for Diuron, Terbutryn and Diquat were 0.009, 0.031and 0.381 μmole L-1 whereas ET50 values were 32.32, 35.89 and 23.45 h, respectively. EC50 values of binary mixtures (B1-B3) were 0.004, 0.01 and 0.012 toxicity units. Tertiary mixtures (T1-T7) had a wide range of EC50 (0.043-2.9E-07) TUs. The mixture toxicity index (MTI) had positive and negative value in mixtures, indicating synergetic and antagonistic effects. Application of the above-mentioned herbicides may severely damage the ecosystem. Our results are the first of its kind in the region and may be considered as a guideline for future studies.

Ratiometric emission of Tb(III)-functionalized Cd-based layered MOFs for portable visual detection of trace amounts of diquat in apples, potatoes and corn

Diquat (DQ) is a typical bipyridine herbicide widely used to control weeds in fields and orchards. The severe toxicity of diquat poses a serious threat to the environment and human health. Metal-organic frameworks (MOFs) have received widespread attention due to their unique physical and chemical properties and applications in the detection of toxic and harmful substances. In this work, a two-dimensional (2D) Tb(III) functionalized MOF Tb(III)@1 (1 = [Cd(HTATB)(bimb)]n·H2O (Cd-MOF), H3TATB = 4,4′,4″-triazine-2,4,6-tribenzoicacid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene) has been prepared and characterized. Tb(III)@1 has excellent optical properties and high water and chemical stability. After the Tb(III) is fixed by the uncoordinated -COO- in the 1 framework, Tb(III)@1 emits the typical green fluorescence of the lanthanide ion Tb(III) through the “antenna effect”. It is worth noting that Tb(III)@1 can be used as a dual emission fluorescence chemical sensor for the ratio fluorescence detection of pesticide DQ, exhibiting a relatively low detection limit of 0.06 nM and a wide detection range of 0–50 nM. After the addition of DQ, a rapid color change of Tb(III)@1 fluorescence from green to blue was observed due to the combined effects of IFE, FRET and dynamic quenching. Therefore, a simple test paper box has been designed for direct on-site determination of pesticide DQ. In addition, the developed sensor has been successfully applied to the detection of DQ in real samples (fruits a Yin-Xia Sun and Bo-Tao Ji contributed equally to this work and should be considered co-first authors.nd vegetables) with satisfactory results. The results indicate that the probe developed in this study has broad application prospects in both real sample detection and actual on-site testing.

Protective effects of taurine against muscle damage induced by diquat in 35\u2009days weaned piglets

BackgroundOxidative stress is a key factor that influences piglets’ health. Taurine plays an imperative role in keeping the biological system from damage. This study was conducted to investigate the protective effect of taurine against muscle injury due to the secondary effect of diquat toxicity.ResultsOur study found that taurine effectively and dose-dependently alleviated the diquat toxicity induced rise of feed/gain, with a concurrent improvement of carcass lean percentage. The plasma content of taurine was considerably increased in a dose-dependent manner. Consequently, dietary taurine efficiently improved the activity of plasma antioxidant enzymes. Furthermore, taurine attenuated muscle damage by restoring mitochondrial micromorphology, suppressing protein degradation and reducing the percentage of apoptotic cells in the skeletal muscle. Taurine supplementation also suppressed the genes expression levels of the antioxidant-, mitochondrial biogenesis-, and muscle atrophy-related genes in the skeletal muscle of piglets with oxidative stress.ConclusionsThese results showed that the dose of 0.60% taurine supplementation in the diet could attenuate skeletal muscle injury induced by diquat toxicity. It is suggested that taurine could be a potential nutritional intervention strategy to improve growth performance.

The experimental study of diquat on the half-Lethal dose and pothological injuny of related organs in wistor rats

Objective: To explore the acute toxicity of Diquat in mice and to calculate the median lethal dose (LD(50)) of Diquat to rats and observe the pathological changes of tissues and organs in rats with different concentrations of Diquat. Methods: Diquat solution of 50 mg/kg was prepared freshly with 1 000 mg of Diquat and dilute the solution with water to a total of 20 ml. A total of 99 healthy adult male Wistar rats were randomly divided into part one, part two and control groups. In the first part, 36 rats were randomly divided into 4 groups: 100 mg/kg group, 200 mg/kg group, 300 mg/kg group and 400 mg/kg group, which were treated with 100 mg/kg, 200 mg/kg, 300 mg/kg and 400 mg/kg of Diquat solution by gavage, respectively. The death and symptoms of poisoning after intragastric administration were recorded, and the maximum tolerated dose and absolute lethal dose were measured. In the second part, 54 rats were randomly divided into 6 groups: 200 mg/kg group, 220 mg/kg group, 240 mg/kg group, 260 mg/kg、280 mg/kg group and 300 mg/kg group, whichwere treated with 200 mg/kg, 220 mg/kg, 240 mg/kg, 260 mg/kg, 280 mg/kg and 300 mg/kg of Diquat solution by gavage, respectively. The survival of rats in different concentration of Diquat was observed and the LD(50) was calculated by Excel processing the formula of Koch's method. The control group were given equal volume water under the same experimental conditions. And moreover, the lungs, kidneys, hearts, livers, and brain tissues were collected and fixed by formaldehyde, embedded by paraffin, and sectioned for histopathological light microscopy. Results: The maximum tolerated dose was 240 mg/kg and the absolute lethal dose was 300 mg/kg. The LD(50) of Diquat for Rats was 280.58 mg/kg. The high-dose group had significantly more organ damage than the low-dose group after diquat poisoning. Conclusion: The determination of the half-lethal dose of diquat, at the same time observed multiple organs damaged in rats after the diquat quickly poisoned. Kidneys, lungs and heart might be the main organ which was heavily damaged. With the extension of observation time, the organ damage of rats exposed to small doses gradually stabilized.

Mitochondrial bioenergetics and locomotor activity are altered in zebrafish (Danio rerio) after exposure to the bipyridylium herbicide diquat

Diquat is a non-selective bipyridylium herbicide which has replaced its sister compound paraquat, as paraquat is associated to an increased risk for Parkinson’s disease. However, the propensity of diquat to propagate reactive oxygen species ensures that diquat remains an exposure risk in non-target organisms. In this study, zebrafish (Danio rerio) embryos were exposed to diquat (1, 10, 100μM) beginning at ∼6h post fertilization for up to 7days to learn more about the mechanisms underlying diquat toxicity during vertebrate development. Zebrafish embryos exposed to diquat for 96h did not show any significant mortality nor deformity compared to controls. Moreover, there was no difference in the timing of hatch, an indicator of stress, for fish exposed to diquat. To determine whether changes in mitochondrial bioenergetics occurred in early development as a response to diquat exposure, oxygen consumption rate was measured in whole embryos. Basal respiration and ATP production were decreased following a 24h diquat exposure at 100μM, suggesting that diquat negatively affects oxidative phosphorylation. We also assessed locomotor behavior as a sensitive endpoint for impaired activity and neurotoxicity. Seven day old (7 dpf) zebrafish treated with diquat at the highest doses tested (10–100μM) showed an increase (hyper-activity) in total distance travelled, velocity, movement cumulative duration, and overall activity compared to unexposed fish. Lastly, in 7d fish, we measured transcripts related to redox balance and apoptosis as diquat has been reported to induce oxidative stress and can affect mitochondrial bioenergetics. Larvae exposed to 10μM diquat showed higher transcript levels of catalase compared to control fish, implying that reactive oxygen species are produced following diquat exposure. Transcript levels of sod1, sod2, bcl2, bax and caspase 3 however did not vary in abundance among treatments with diquat. This study improves mechanistic understanding of diquat in fish at early stages of development and presents evidence that diquat disrupts mitochondrial bioenergetics and behavior.

Effect of diquat-induced oxidative stress on iron metabolism in male Fischer-344 rats

Diquat toxicity causes iron-mediated oxidative stress; however, it remains unclear how diquat affects iron metabolism. Here, we examined the effect of diquat-induced oxidative stress on iron metabolism in male Fischer-344 rats, with particular focus on gene expression. Hepatic nonheme iron content was unchanged until 20h after diquat treatment. Hepatic free iron levels increased markedly in the early stages following treatment and remained elevated for at least 6h, resulting in severe hepatotoxicity, until returning to control levels at 20h. The level of hepatic ferritin, especially the H-subunit, increased 20h after diquat treatment due to elevated hepatic ferritin-H mRNA expression. These results indicate that early elevated levels of free iron in the liver of diquat-treated rats cause hepatotoxicity, and that this free iron is subsequently sequestered by ferritin synthesized under conditions of oxidative stress, thus limiting the pro-oxidant challenge of iron. The plasma iron concentration decreased at 6 and 20h after diquat treatment, whereas the level of plasma interleukin-6 increased markedly at 3h and remained high until 20h. In the liver of diquat-treated rats, expression of hepcidin mRNA was markedly upregulated at 3 and 6h, whereas ferroportin mRNA expression was downregulated slightly at 20h. Transferrin receptor 1 mRNA expression was significantly upregulated at 3, 6, and 20h. These results indicate that inhibition of iron release from iron-storage tissues, through stimulation of the interleukin-6-hepcidin-ferroportin axis, and enhanced iron uptake into hepatocytes, mediated by transferrin receptor 1, cause hypoferremia.

Wheat Bran Protects Fischer-344 Rats from Diquat-Induced Oxidative Stress by Activating Antioxidant System: Selenium as an Antioxidant

Wheat bran had a protective effect against diquat toxicity in rats fed a purified diet (PD). We studied the effects of wheat bran on the antioxidant system in the liver of rats treated with saline and diquat. Although feeding wheat bran did not affect the concentration of hepatic non-protein sulfhydryl or the activity of glucose 6-phosphate dehydrogenase in the saline-injected rats, these values were significantly higher in the rats fed PD containing wheat bran (W-PD) than in rats fed only PD after administering diquat. The glutathione peroxidase and reductase activities were significantly elevated by wheat bran in the saline-injected rats. Although the glutathione peroxidase activity was unchanged in both the PD-fed rats and W-PD-fed rats after the diquat treatment, the glutathione reductase activity was significantly decreased in both the PD-fed and W-PD-fed rats. Feeding the rats with PD containing 0.15 ppm selenium as well as with W-PD elevated the activity of hepatic glutathione peroxidase and attenuated the diquat toxicity. These results indicate that wheat bran protected against diquat toxicity by activating the hepatic antioxidant system, and that selenium was the key antioxidant in wheat bran.

Oxidative stress induced by loss of Cu,Zn-superoxide dismutase (SOD1) or superoxide-generating herbicides causes axonal degeneration in mouse DRG cultures

Axonal degeneration is a common pathologic feature in peripheral neuropathy, neurodegenerative disease, and normal aging. Oxidative stress may be an important mechanism of axonal degeneration, but is underrepresented among current experimental models. To test the effects of loss of the antioxidant enzyme Cu,Zn-superoxide dismutase (SOD1) on axon survival, we cultured dorsal root ganglion (DRG) neurons from SOD1 knockout mice. Beginning as early as 48-72 h, we observed striking degeneration of Sod1-/- axons that was prevented by introduction of human SOD1 and was attenuated by antioxidant treatment. To test susceptibility to increased superoxide production, we exposed wild-type DRGs to the redox-cycling herbicides paraquat and diquat (DQ). Dose-dependent axon degeneration was observed, and toxicity of DQ was exacerbated by SOD1 deficiency. MTT staining suggested that DRG axons are more susceptible to injury than their parent cell bodies in both paradigms. Taken together, these data demonstrate susceptibility of DRG axons to oxidative stress-mediated injury due to loss of SOD1 or excess superoxide production. These in vitro models provide a novel means of investigating oxidative stress-mediated injury to axons, to improve our understanding of axonal redox control and dysfunction in peripheral neuropathy.

Protective Effects of Wheat Bran against Diquat Toxicity in Male Fischer-344 Rats

After injection with 0.1 mmol diquat/kg body weight, survival time was markedly shorter in Fischer-344 rats fed a purified diet than in rats fed a regular diet, and much more severe hepatotoxicity and nephrotoxicity were observed in the former than in the latter. The longer the feeding period on the purified diet, the shorter the survival time after diquat administration. These results indicate that the purified diet lacked components present in the regular diet that had protective effects against diquat toxicity. These two diets had nearly the same composition and content of vitamins and minerals. We tested the ingredients of the regular diet to determine which ones reduce diquat toxicity. We found that wheat bran had a protective effect, but that rice bran and bean-curd refuse (okara) did not.

Relationship between body iron stores and diquat toxicity in male Fischer-344 rats

The effects of body iron stores on diquat (DQ)-induced toxicity were examined in male Fischer-344 rats, which are sensitive to this herbicide. The rats (5 weeks old) were fed diets containing 40 (lower iron storage [LIS] group) or 320 ppm iron (higher iron storage [HIS] group) for 5 weeks. The concentrations of nonheme iron and ferritin in the liver and kidney were significantly higher in the HIS group than in the LIS group (P<0.0001), although there was no significant differences between the HIS and LIS groups in hematological parameters, including red blood cell count, hemoglobin concentration, and mean corpuscular volume. Three hours after administration of 0.1 mmol DQ/kg, serum alanine aminotransferase and urea nitrogen were significantly higher than in controls (saline injection) for both the LIS and HIS groups (P<0.01), and, after DQ injection, these parameters were significantly higher in the HIS group than in the LIS group (P<0.01). When the rats were injected with 0.075 or 0.1 mmol DQ/kg, the survival time was significantly shorter in the HIS group than in the LIS group (P<0.05). These findings suggest that higher body iron stores result in more severe DQ toxicity in Fischer-344 rats.

Renal failure and corrosive airway and gastrointestinal injury after ingestion of diluted diquat solution

A 66-year-old man ingested 200 mL of Dexol Industries Weed and Grass Killer Concentrate (Torrance, CA), which contains 1.84% diquat dibromide, a herbicide structurally similar to paraquat. He remained asymptomatic for 8 hours, and then a sore throat and vomiting developed. Twenty hours after ingestion, esophagitis, mucositis, epiglottitis, and acute renal failure developed, from which he slowly recovered. This is the first report of systemic diquat toxicity from ingestion of a diluted diquat solution.

Toxicity of hexazinone and diquat to green algae, diatoms, cyanobacteria and duckweed

Hexazinone and diquat are two broad-spectrum contact herbicides used in a variety of crop and non-crop applications. Both pesticides are highly water soluble and persistent in the aquatic system. Hexazinone is mobile in soil and, thus, the potential for leaching into ground water and for overland runoff into surface water is high; diquat, however, is rapidly bound by soil and sediment to a biologically inactive form, at least temporarily. Toxicity to green algae (two species), diatoms (two species) and cyanobacteria (five species) was determined using inhibition of 14C uptake. Toxicity to the floating vascular plant, duckweed, was tested by measuring seven-day growth inhibition. Test organisms exhibited large differences in sensitivity to both herbicides. The green algae, diatoms, and duckweed (all eukaryotes) were more sensitive to hexazinone than were cyanobacteria (prokaryotes). Mean concentrations at which 50% inhibition occurred in these groups were 0.01 (green algae), 0.05 (diatoms), 0.07 (duckweed), and 0.6 (cyanobacteria) mg hexazinone per litre, respectively. In contrast, green algae were comparatively tolerant of diquat (EC 50values approximately 0.6 mg l −1), while the cyanobacteria and diatoms were much more sensitive (mean EC 50values of 0.074 and 0.079 mg diquat per litre). Duckweed showed the greatest sensitivity to diquat, with 50% inhibition of growth occurring at 0.004 mg l −1. That some non-target aquatic plants are susceptible to diquat toxicity at less than 0.01 mg l −1is significant, as most methods of diquat analysis have minimum detection limits of 0.01 to 0.05 mg l −1. Therefore, algae and vascular aquatic plants may suffer phytotoxic effects in a contaminated water body even when diquat is undetectable chemically. Differential sensitivity to herbicide contaminants among taxonomic groups of plants may have ecological consequences. Cyanobacteria may produce neuro- and hepato-toxins and constitute a poor food resource for higher trophic levels relative to the other organisms tested. Contamination of surface water with hexazinone may degrade water quality for wildlife, both by causing food reduction and habitat loss through inhibition of green algae, diatoms and macrophytes, and by allowing the proliferation of cyanobacteria. Varying responses among the different test algae to the two herbicides under study indicated that a wide taxonomic range of test species is necessary in evaluating the impacts of contaminants in aquatic systems.

A Rebuttal To: “The Toxicity of Diquat, Endothall, and Fluridone to the Early Life Stages of Fish”

A Rebuttal To: “The Toxicity of Diquat, Endothall, and Fluridone to the Early Life Stages of Fish”

The Toxicity of Diquat, Endothall, and Fluridone to the Early Life Stages of Fish

ABSTRACT While most aquatic herbicides have undergone some toxicity testing for effects on non-target aquatic organisms, little of this testing has been conducted on early life stages of gamefish found in lakes undergoing treatment. Commercial formulations of diquat, endothall, and fluridone were selected for acute toxicity testing using very early life stages of walleye (Stizostedion vitreum), largemouth bass (Micropterus salmoides), and smallmouth bass (Micropterus dolomieu). In addition, the rates of diquat photodegradation and uptake by sediment were determined. These results were used to predict diquat concentrations in lakes of various depths. The results of the toxicity tests were compared to the predicted concentrations. Diquat, with 96-h LCSOs of 0.74–4.9 mg/L, was more toxic to these early life stages than endothall or fluridone, with 96-h LC50s of 16–130 mg/L and 1.8–13 mg/L respectively. The LC50s for endothall and fluridone were at least one order of magnitude greater than the labeled application concentrations. As the LC50s for diquat were very close to the predicted concentration, the safety margin for the use of diquat appears to be very small.

Evidence for redox cycling of diquat in rat small intestine

It has previously been established that acute diquat (1,1′-ethylene, 2,2′-bipyridilium) toxicity in the rat is associated with stimulation of net fluid secretion into the gastrointestinal tract. We have examined the possibility that the mechanism of diquat toxicity in the small intestine involves redox cycling of the bipyridyl leading to a disturbance of biochemical function and oxidative stress. Experiments performed in vitro showed that diquat (10 μM to 1 mM) produced an increase in activity of the pentose phosphate pathway in rat small intestinal tissue slices, suggesting that there was oxidation of NADPH even at concentrations of diquat which do not cause intestinal fluid secretion in anaesthetized rats. When the effect of diquat on pentose phosphate activity was measured in rats in situ at a dose which causes maximal fluid secretion [50 mM diquat dibromide (DQBr 2)], production of 14CO 2 from [1- 14C]-glucose increased by 278±28% (N = 4) within 1 hr of exposure to diquat. Under these same conditions, the tissue content of NADPH in the proximal small intestine was significantly depleted, though there was no corresponding increase in NADP + concentration. Diquat had no effect on tissue concentrations of either the reduced or oxidized forms of NAD. It is likely that NADPH oxidation at low diquat concentrations can be adequately compensated for by mechanisms within the tissue which protect against oxidative stress. However, the data also suggest that diquat-induced fluid secretion in the rat small intestine is associated with redox cycling of bipyridyl leading to depletion of NADPH.

Diquat-Induced Oxidative Damage in BCNU-Pretreated Hepatocytes of Mature and Old Rats

The effects of postmaturational aging on the toxicity of diquat, a redox cycling compound, were investigated in hepatocytes that were isolated from mature (6 months) and old (27 months) male Fischer 344 rats and pretreated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of glutathione reductase. The hepatocytes were incubated for 2 hr with 0, 0.5, or 2.0 mM diquat dibromide, and samples were taken at various time points for measurements of glutathione, glutathione disulfide, thiobarbituric acid reactive substances, lactate dehydrogenase leakage, protein sulfhydryl groups, and protein carbonyl groups. Diquat cytotoxicity was intensified in hepatocytes of old rats compared with those of mature rats, and the enhanced toxicity was associated with increased lipid peroxidation and protein carbonyl formation. However, the enhanced toxicity in old rat hepatocytes was also accompanied by a decrease in diquat-induced GSH oxidation and there was no difference in protein sulfhydryl loss. Concentrations of total nonheme iron and low-molecular-weight chelatable Fe 2+, measured with ferene as the chromogen, were several times higher in freshly isolated hepatocytes of old rats than in those of mature rats. We hypothesize that the age-associated enhancement of diquat toxicity could be due to an increased availability of iron for reaction with diquat-generated hydrogen peroxide and for stimulation of lipid and protein oxidation.

Inhibition of diquat-induced lipid peroxidation and toxicity in precision-cut rat liver slices by novel antioxidants

The ability of the novel antioxidants U-74,006F and U-78,517G and a known antioxidant ( N,N′-diphenyl- p-phenylenediamine, (DPPD)) to inhibit chemically induced (diquat dibromide) oxidative stress was examined in precision-cut liver slices. Previous studies in rat liver microsomes demonstrated the ability of these antioxidants to inhibit lipid peroxidation without preventing redox cycling of diquat. Diquat (1 m m) initiated lipid peroxidation in liver slices prepared from F344 rats. A 30-min preincubation with antioxidants inhibited formation of thiobarbituric acid reactive substances to control levels; ethane evolution, when elevated, was also inhibited by antioxidants. The toxicity of diquat (100 μ m-3 m m) was evaluated in liver slices; 1 and 3 m m diquat caused decreases in intracellular K + and intracellular LDH. Preincubation with antioxidants substantially decreased the toxicity of diquat as indicated by K + and LDH. Diquat significantly decreased total glutathione levels in the slices; the antioxidants did not significantly inhibit this diquat-dependent effect. In summary, diquat, a compound which undergoes redox cycling and produces oxidative stress, was shown to produce lipid peroxidation, glutathione depletion, and toxicity in liver slices. Two experimental antioxidants, a 21-aminosteroid (U-74,006F) and a trolox-amine (U-78,517G) as well as a known antioxidant (DPPD) were shown to be effective in preventing lipid peroxidation and reducing the subsequent toxicity.

The Protective Effect of Sulfite on Menadione‐ and Diquat‐Induced Cytotoxicity in Isolated Rat Hepatocytes

Menadione and diquat cause toxicity in isolated hepatocytes. The toxicities of both menadione and diquat are primarily due to redox cycling and consequent oxidative stress. Menadione toxicity, however, has another component as the compound also possesses alkylating and oxidating properties allowing it to interact directly with cellular nucleophiles. Sulfite afforded considerable protection of isolated rat hepatocytes against the toxicity of menadione. This protective effect of sulfite may have several components. Sulfite effectively competed with glutathione (GSH) for conjugation with menadione, sparing intracellular GSH which may continue to detoxify reactive oxygen species formed through menadione redox cycling. The menadione sulfite conjugate undergoes much slower redox cycling than both menadione and the menadione glutathione conjugate. Sulfite also showed some degree of protection of hepatocytes from the toxicity of diquat. Diquat is a "pure" redox cycling agent and the protective effect of sulfite may involve the liberation of GSH from GSSG by sulfitolysis. This would again bolster intracellular GSH levels allowing further GSH-dependent detoxification of reactive oxygen species through cellular GSH peroxidases. In conclusion, our data illustrate the potential of inorganic sulfite to support the intracellular detoxification function of GSH, both against reactive electrophilic metabolites and against agents undergoing redox cycling.

Effect of sediment on estimates of diquat toxicity in laboratory microcosms

The influence of sediment on the toxicity of the herbicide diquat to microbial communities was examined in laboratory microcosms. Microbial communities collected on polyurethane foam (PF) substrata were used to establish replicate microcosms with and without sediment. After a single application of diquat, microbial community structure and function were evaluated. Three weeks after diquat treatment, communities in microcosms without sediment exhibited decreased biomass production, increased alkaline phosphatase activity, decreased dissolved oxygen production and altered protozoan species richness and composition at maximum allowable toxicant concentrations (MATCs) of 0.04–21.9 mg diquat 1 −1. In microcosms amended with natural lake sediments, communities were initially affected by diquat treatment, but, by 2 weeks, dosed communities were indistinguishable from controls. Diquat disappeared rapidly in sediment-amended microcosms and could not be detected ( < 0.1 mg diquat 1 −1) in any but the highest treatment after 1 week. In microcosms without sediment, 44–75% of the diquat remained in the three highest treatments after 3 weeks. Results stress the consideration of the environmental fate of chemicals in different ecosystems when designing conditions under which the toxicity of a chemical is tested. Simplistic experimental designs for toxicological studies may overestimate adverse environmental effects.