Residue behavior, transfer and risk assessment of tolfenpyrad, dinotefuran and its metabolites during tea growing and tea brewing.

BACKGROUND: Tolfenpyrad and dinotefuran are two representative pesticides used for pest control in tea gardens. Their application may bring about a potential risk to the health of consumers. Therefore, it is essential to investigate the residue behavior, transfer and risk assessment of tolfenpyrad, dinotefuran and metabolites from tea garden to teacup. RESULTS: An effective analytical method was established and validated to simultaneously determine tolfenpyrad, dinotefuran and its metabolites (DN and UF) in tea. The average recoveries of tolfenpyrad, dinotefuran, DN and UF were in the range 72.1-106.3%, with relative standard deviations lower than 11.8%. On the basis of the proposed method, the dissipation of tolfenpyrad and dinotefuran in fresh tea leaves followed first-order kinetics models with half-lives of 4.30-7.33 days and 4.65-5.50 days, respectively. With application amounts of 112.5-168.75 g a.i. ha-1 once or twice, the terminal residues of tolfenpyrad and total dinotefuran in green tea were lower than 19.6 and 7.13 mg kg-1 , respectively, and below their corresponding maximum residue limits . The leaching rates of tolfenpyrad and total dinotefuran during the tea brewing were in the ranges 1.4-2.3% and 93.7-98.1%, respectively. CONCLUSION: Tolfenpyrad and dinotefuran in tea were easily degraded. The RQc and RQa values for tolfenpyrad were 37.6% and 5.4%, which were much higher than for dinotefuran at 24.7% and 0.84%, respectively. The data indicated that there was no significant health risk in tea for consumers at the recommended dosages. The results provide scientific data regarding the reasonable use of tolfenpyrad and dinotefuran aiming to ensure safe tea consuption. © 2021 Society of Chemical Industry.

Inhibitors of tri- and tetra- polyamine oxidation, but not diamine oxidation, impair the initial stages of wound-induced suberization.

The mechanisms regulating, and modulating potato wound-healing processes are of great importance in reducing tuber infections, reducing shrinkage and maintaining quality and nutritional value for growers and consumers. Wound-induced changes in tuber polyamine metabolism have been linked to the modulation of wound healing (WH) and in possibly providing the crucial amount of H2O2 required for suberization processes. In this investigation we determined the effect of inhibition of specific steps within the pathway of polyamine metabolism on polyamine content and the initial accumulation of suberin polyphenolics (SPP) during WH. The accumulation of SPP represents a critical part of the beginning or inchoate phase of tuber WH during closing-layer formation because it serves as a barrier to bacterial infection and is a requisite for the accumulation of suberin polyaliphatics which provide the barrier to fungal infection. Results showed that the inhibitor treatments that caused changes in polyamine content generally did not influence wound-induced accumulation of SPP. Such lack of correlation was found for inhibitors involved in metabolism and oxidation of putrescine (arginine decarboxylase, ornithine decarboxylase, and diamine oxidase). However, accumulation of SPP was dramatically reduced by treatment with guazatine, a potent inhibitor of polyamine oxidase (PAO), and methylglyoxal-bis(guanylhydrazone), a putative inhibitor of S-adenosylmethione decarboxylase which may also cross-react to inhibit PAO. The mode of action of these inhibitors is presumed to be blockage of essential H2O2 production within the WH cell wall. These results are of great importance in understanding the mechanisms modulating WH and ultimately controlling related infections and associated postharvest losses.

In silico screening of GMQ-like compounds reveals guanabenz and sephin1 as new allosteric modulators of acid-sensing ion channel 3.

Acid-sensing ion channels (ASICs) are voltage-independent cation channels that detect decreases in extracellular pH. Dysregulation of ASICs underpins a number of pathologies. Of particular interest is ASIC3, which is recognised as a key sensor of acid-induced pain and is important in the establishment of pain arising from inflammatory conditions, such as rheumatoid arthritis. Thus, the identification of new ASIC3 modulators and the mechanistic understanding of how these compounds modulate ASIC3 could be important for the development of new strategies to counteract the detrimental effects of dysregulated ASIC3 activity in inflammation. Here, we report the identification of novel ASIC3 modulators based on the ASIC3 agonist, 2-guanidine-4-methylquinazoline (GMQ). Through a GMQ-guided in silico screening of Food and Drug administration (FDA)-approved drugs, 5 compounds were selected and tested for their modulation of rat ASIC3 (rASIC3) using whole-cell patch-clamp electrophysiology. Of the chosen drugs, guanabenz (GBZ), an α2-adrenoceptor agonist, produced similar effects to GMQ on rASIC3, activating the channel at physiological pH (pH 7.4) and potentiating its response to mild acidic (pH 7) stimuli. Sephin1, a GBZ derivative that lacks α2-adrenoceptor activity, has been proposed to act as a selective inhibitor of a regulatory subunit of the stress-induced protein phosphatase 1 (PPP1R15A) with promising therapeutic potential for the treatment of multiple sclerosis. However, we found that like GBZ, sephin1 activates rASIC3 at pH 7.4 and potentiates its response to acidic stimulation (pH 7), i.e. sephin1 is a novel modulator of rASIC3. Furthermore, docking experiments showed that, like GMQ, GBZ and sephin1 likely interact with the nonproton ligand sensor domain of rASIC3. Overall, these data demonstrate the utility of computational analysis for identifying novel ASIC3 modulators, which can be validated with electrophysiological analysis and may lead to the development of better compounds for targeting ASIC3 in the treatment of inflammatory conditions.

Neonicotinoid insecticidal seed-treatment on corn contaminates interseeded cover crops intended as habitat for beneficial insects.

Neonicotinoid seed treatments are extensively used to systemically protect corn from invertebrate herbivory. Interseeding cover crops can promote beneficial insect communities and their ecosystem services such as predation on pests, and this practice is gaining interest from farmers. In this study, cereal rye (Secale cereale) and hairy vetch (Vicia villosa) were planted between rows of early vegetative corn that had been seed-treated with thiamethoxam. Thiamethoxam and its insecticidal metabolite, clothianidin were quantified in cover crop leaves throughout the growing season. Thiamethoxam was present in cereal rye at concentrations ranging from 0 to 0.33 ± 0.09 ng/g of leaf tissue and was detected on six out of seven collection dates. Cereal rye leaves contained clothianidin at concentrations from 1.05 ± 0.22 to 2.61 ± 0.24 ng/g and was present on all sampling dates. Both thiamethoxam and clothianidin were detected in hairy vetch on all sampling dates at rates ranging from 0.10 ± 0.05 to 0.51 ± 0.11 ng/g and 0.56 ± 0.15 to 9.73 ± 5.04 ng/g of leaf tissue, respectively. Clothianidin was measured at a higher concentration than its precursor, thiamethoxam, in both plant species on every sampling date. Neonicotinoids entering interseeded cover crops from adjacent treated plants is a newly discovered route of exposure and potential hazard for non-target beneficial invertebrates. Future research efforts should examine the effects of systemic insecticides on biological communities in agroecosystems whose goal is to diversify plant communities using methods such as cover cropping.

Determinations of dinotefuran and metabolite levels before and after household coffee processing in coffee beans using solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry.

BACKGROUND: Coffee is one of the most popular beverages in the world. However, as daily consumables, coffee beans may contain pesticide residues that are capable of causing adverse health effects. Thus, we investigated residue dynamics in coffee beans using supervised field trials under Good Agricultural Practice conditions and determined the effects of household coffee processing on the coffee-bean pesticide residues dinotefuran and its metabolites 1-methyl-3-(tetrahydro-3-furylmethyl) urea (UF) and 1-methyl-3-(tetrahydro-3-furylmethyl) guanidine (DN). RESULTS: The recovery rate of dinotefuran and its metabolites UF and DN was in the range 73.5%-106.3%, with a relative SD < 10%. The limits of detection and limits of quantification for dinotefuran, UF and DN were all 0.003 and 0.01 mg kg-1 , respectively. Dissipation experiments were conducted over 2015 and 2016 and showed a mean half-life of 40.8 days. Coffee processing procedures were performed as described for traditional household coffee processing in Ethiopia. Dinotefuran contents were reduced by 44.4%-86.7% with washing of coffee beans and the roasting process reduced these contents by 62.2%-100%. DN residues were not detected in roasted coffee beans before day 21 or in brewed coffee before day 35 and UF residues were not detected in brewed coffee before day 35. Kruskal-Wallis analyses indicated large variations in the stability of pesticide residues between processing methods (P ≤ 0.05). Reductions of pesticide concentrations with washing were also significantly lower than those following roasting (P = 0.0001) and brewing processes (P = 0.002). Moreover, processing factors were less than one for all processing stages, indicating reductions of pesticides contents for all processing stages. CONCLUSION: The cumulative effects of the three processing methods are of paramount importance with respect to an evaluation of the risks associated with the ingestion of pesticide residues, particularly those in coffee beans. © 2018 Society of Chemical Industry.

Effects of phosphogypsum, superphosphate, and dicyandiamide on gaseous emission and compost quality during sewage sludge composting.

This study investigated the effects of phosphogypsum, superphosphate, and dicyandiamide on gaseous emission and compost quality during sewage sludge composting. Results showed that phosphogypsum reduced ammonia (NH3) and methane (CH4) emissions but increased nitrous oxide (N2O) emission. Superphosphate simultaneously reduced NH3, N2O and CH4 emissions. Dicyandiamide markedly reduced N2O emission during composting. Combination of phosphogypsum and dicyandiamide reduced CH4 and N2O emissions by 75.6% and 86.4%, while NH3 emission was increased by 22.0%. Combination of superphosphate and dicyandiamide reduced NH3, CH4 and N2O emissions by 12.3%, 81.0% and 88.2%, respectively. More importantly, with the addition of 10% initial raw materials, phosphogypsum and superphosphate conserved nitrogen and improved compost quality by introducing additional nutrients.

Phosphono Bisbenzguanidines as Irreversible Dipeptidomimetic Inhibitors and Activity-Based Probes of Matriptase-2.

Matriptase-2, a type II transmembrane serine protease, plays a key role in human iron homeostasis. Inhibition of matriptase-2 is considered as an attractive strategy for the treatment of iron-overload diseases, such as hemochromatosis and ß-thalassemia. In the present study, synthetic routes to nine dipeptidomimetic inactivators were developed. Five active compounds (41-45) were identified and characterized kinetically as irreversible inhibitors of matriptase-2. In addition to a phosphonate warhead, these dipeptides possess two benzguanidine moieties as arginine mimetics to provide affinity for matriptase-2 by binding to the S1 and S3/S4 subpockets, respectively. This binding mode was strongly supported by covalent docking analysis. Compounds 41-45 were obtained as mixtures of two diastereomers and were therefore separated into the single epimers. Compound 45 A, with S configuration at the N-terminal amino acid and R configuration at the phosphonate carbon atom, was the most potent matriptase-2 inactivator with a rate constant of inactivation of 2790 m(-1) s(-1) and abolished the activity of membrane-bound matriptase-2 on the surface of intact cells. Based on the chemotyp of phosphono bisbenzguanidines, the design and synthesis of a fluorescent probe (51 A) by insertion of a coumarin label is described. The in-gel fluorescence detection of matriptase-2 was demonstrated by applying 51 A as the first activity-based probe for this enzyme.

Residues of neonicotinoids and their metabolites in honey and pollen from sunflower and maize seed dressing crops.

A study was carried out to evaluate the possible presence of thiamethoxam, clothianidin and imidacloprid, as well as the metabolic breakdown products of these three neonicotinoids in pollen and honey obtained from brood chamber combs of honeybee colonies located next to sunflower and maize crops from coated seeds. Samples were analyzed by liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry detector, in combination with accurate mass tools such as diagnostic ions by exact mass, chlorine mass filters, and MS/MS experiments. The presence of thiamethoxam and clothianidin was confirmed in some of the pollen samples analyzed. Moreover, different metabolites of neonicotinoids were tentatively detected in the pollen and honey samples collected. The results suggested that four metabolites were found in the honey samples, while for pollen samples eleven metabolites were identified; among these, five were considered for the first time as metabolic breakdown products in sunflower and maize plants.

Uptake of Neonicotinoid Insecticides by Water-Foraging Honey Bees (Hymenoptera: Apidae) Through Guttation Fluid of Winter Oilseed Rape.

The water-foraging activity of honey bees (Apis mellifera L.) on guttation fluid of seed-coated crops, such as winter oilseed rape (WOR; Brassica napus L.), has not yet been evaluated. We analyzed the uptake of active substances (a.s.) in guttation fluid by evaluating residues of honey-sac contents. In autumn, insecticide residues of up to 130 µg a.s. per liter were released in WOR guttation fluid; this concentration is noticeably lower than levels reported in guttation fluid of seed-coated maize. Until winter dormancy, the concentrations declined to <30 µg a.s. per liter. In spring, residues were linked to prewintered plants and declined steadily until flowering. The maximum release of residues in guttation fluid of seed-coated WOR occurs on the first leaves in autumn when the colonies' water demand decreases. For the first time, proof for the uptake of guttation fluid from seed-coated WOR by honey bees was provided by measuring residues in individual honey-sac contents. In total, 38 out of 204 samples (19%) showed residues of thiamethoxam at concentrations ranging from 0.3 to 0.95 µg per liter while the corresponding concentrations in guttation fluid of WOR varied between 3.6 to 12.9 µg thiamethoxam per liter. The amounts of thiamethoxam we found in the honey sacs of water-foraging honey bees were therefore below the thresholds in nectar and pollen that are considered to have negative effects on honey bees after chronic exposure.

Concentrations of neonicotinoid insecticides in honey, pollen and honey bees (Apis mellifera L.) in central Saskatchewan, Canada.

Neonicotinoid insecticides (NIs) and their transformation products were detected in honey, pollen and honey bees, (Apis mellifera) from hives located within 30 km of the City of Saskatoon, Saskatchewan, Canada. Clothianidin and thiamethoxam were the most frequently detected NIs, found in 68 and 75% of honey samples at mean concentrations of 8.2 and 17.2 ng g(-1) wet mass, (wm), respectively. Clothianidin was also found in >50% of samples of bees and pollen. Concentrations of clothianidin in bees exceed the LD50 in 2 of 28 samples, while for other NIs concentrations were typically 10-100-fold less than the oral LD50. Imidaclorpid was detected in ∼30% of samples of honey, but only 5% of pollen and concentrations were

Consequences of the matrix effect on recovery of dinotefuran and its metabolites in green tea during tandem mass spectrometry analysis.

Determining the residues of dinotefuran and its metabolites (MNG, UF, and DN) is highly problematic because of their polar characteristics. Additionally, tea contains many compounds that can interfere with residue analysis. Thus, the aim of the present study was to refine the extraction method that assures good recoveries for dinotefuran and its metabolites and removes most of the matrix components in green tea using liquid chromatography-tandem mass spectrometry (LC/MS/MS). We attempted to increase the extraction efficiency of the QuEChERS method by selecting the appropriate solvents among ethyl acetate, acetone, isopropanol, 25% methanol in acetonitrile, and methanol. We found that methanol was the best extraction solvent for dinotefuran and its polar metabolites in dry green tea samples; however, due to a limitation of an appropriate partitioning salt, acetonitrile was used as the extraction solvent. Matrix enhancement and suppression effects were observed for all analytes, which made the recovery rates variable. DN recovery was <70% when compared with matrix-matched calibration, whereas it was within the acceptable range (70-120%) when compared with solvent calibration. The opposite was observed for MNG and dinotefuran due to a matrix suppression effect. UF recovery was consistent in both matrix-matched and solvent calibrations despite having little suppressive effect. The method was successfully applied and dinotefuran and its metabolite residues were found in field-incurred green tea samples. The current findings suggest that using methanol as an appropriate QuEChERS solvent for problematic polar pesticides and investigating a suitable partitioning salt would considerably strengthen the practical impact of such data.

Degradation dynamics of the insecticide: clothianidin (Dantop 50 % WDG) in a tea field ecosystem.

The fate of clothianidin [(E)-1-(2-chloro-1, 3-thiazol-5-ylmethyl)-3-methyl-2-nitroguanidine] applied to tea plant was studied at two location in West Bengal, India. The insecticide was applied in Tea field at two doses @30 and 60 g.a.i./ha during June-July 2009. Solid-phase extraction and liquid-liquid extraction was employed for the determination of this insecticide in tea samples. Clothianidin residues were analyzed and estimated quantitatively by HPLC at λ(max) 250 nm. The observed half life values of made tea and green tea leaf ranges from 3.71 to 4.07 days and 4.07 to 4.49 days respectively.

A new arginase enzymatic reactor: development and application for the research of plant-derived inhibitors.

This work was dedicated to the development of a new micro immobilized enzyme reactor (IMER) by using an in situ procedure. Arginase was covalently immobilized on an ethylenediamine (EDA) monolithic convective interaction media (CIM) disk (12mm × 3mm i.d.) previously derivatized with glutaraldehyde. The activity of this IMER was investigated by inserting this micro-IMER in a HPLC system. The effect of the arginase inhibitors was evaluated by the simultaneous injection of each inhibitor with the nitro guanidino benzene (NGB) substrate. The relative IC50 values were found in agreement with those derived by the conventional spectrometric method. This arginase micro-IMER system was also used to study the effects of plant-derived products on the arginase activity. The pet ether extract from the stem bark of the plant Ficus glomerata Roxob. and the procyanidin oligomers of cocoa and chocolate inhibit the arginase activity. Our results confirmed the direct effect of some plant extracts on the arginase activity and their interest in therapies for treating several NO-dependent smooth disorders.

Integrating surface plasmon resonance biosensor-based interaction kinetic analyses into the lead discovery and optimization process.

Surface plasmon resonance biosensor technology has come of age and become an important tool for drug discovery. It is a label-free biophysical technique for the kinetic analysis of molecular interactions that provides exceptionally information-rich data. Recent improvements in sensitivity, experimental design, data analysis and sample throughput makes it suitable for use throughout the drug-discovery process. This article outlines the use of SPR biosensor technology for small-molecule drug discovery and exemplifies how it complements other techniques. The technology is especially valuable for fragment-based lead discovery since it has the required sensitivity and throughput for screening of fragment libraries. Hits can be identified with respect to multiple criteria, defined by the experimental design used for screening. Expansion of hits and subsequent characterization and optimization of leads can be performed with a variety of experiments exploiting the kinetic resolution of the technology. Leads identified by this strategy can therefore be extensively characterized with respect to their interactions, with their target as well as with nontarget proteins. Although it may take some time for the methods to become well established, and for the research community to reach proficiency and fully embrace the information-rich data that can be obtained, it can be predicted that this technology will be widely used for drug discovery within the near future. It is expected that the technology will be particularly important for fragment-based strategies and integrated with other experimental technologies as well as with computational methods.

Suppression of grasshopper sound production by nitric oxide-releasing neurons of the central complex.

The central complex of acridid grasshoppers integrates sensory information pertinent to reproduction-related acoustic communication. Activation of nitric oxide (NO)/cyclic GMP-signaling by injection of NO donors into the central complex of restrained Chorthippus biguttulus females suppresses muscarine-stimulated sound production. In contrast, sound production is released by aminoguanidine (AG)-mediated inhibition of nitric oxide synthase (NOS) in the central body, suggesting a basal release of NO that suppresses singing in this situation. Using anti-citrulline immunocytochemistry to detect recent NO production, subtypes of columnar neurons with somata located in the pars intercerebralis and tangential neurons with somata in the ventro-median protocerebrum were distinctly labeled. Their arborizations in the central body upper division overlap with expression patterns for NOS and with the site of injection where NO donors suppress sound production. Systemic application of AG increases the responsiveness of unrestrained females to male calling songs. Identical treatment with the NOS inhibitor that increased male song-stimulated sound production in females induced a marked reduction of citrulline accumulation in central complex columnar and tangential neurons. We conclude that behavioral situations that are unfavorable for sound production (like being restrained) activate NOS-expressing central body neurons to release NO and elevate the behavioral threshold for sound production in female grasshoppers.

Inhibition of the mitochondrial permeability transition by creatine kinase substrates. Requirement for microcompartmentation.

Mitochondria from transgenic mice, expressing enzymatically active mitochondrial creatine kinase in liver, were analyzed for opening of the permeability transition pore in the absence and presence of creatine kinase substrates but with no external adenine nucleotides added. In mitochondria from these transgenic mice, cyclosporin A-inhibited pore opening was delayed by creatine or cyclocreatine but not by beta-guanidinopropionic acid. This observation correlated with the ability of these substrates to stimulate state 3 respiration in the presence of extramitochondrial ATP. The dependence of transition pore opening on calcium and magnesium concentration was studied in the presence and absence of creatine. If mitochondrial creatine kinase activity decreased (i.e. by omitting magnesium from the medium), protection of permeability transition pore opening by creatine or cyclocreatine was no longer seen. Likewise, when creatine kinase was added externally to liver mitochondria from wild-type mice that do not express mitochondrial creatine kinase in liver, no protective effect on pore opening by creatine and its analog was observed. All these findings indicate that mitochondrial creatine kinase activity located within the intermembrane and intercristae space, in conjunction with its tight functional coupling to oxidative phosphorylation, via the adenine nucleotide translocase, can modulate mitochondrial permeability transition in the presence of creatine. These results are of relevance for the design of creatine analogs for cell protection as potential adjuvant therapeutic tools against neurodegenerative diseases.

Synthesis and in vitro evaluation of N,N'-diphenyl and N-naphthyl-N'-phenylguanidines as N-methyl-D-aspartate receptor ion-channel ligands.

A series of N,N'-diphenyl and N-naphthyl-N'-phenyl guanidine derivatives was synthesized as potential N-methyl-D-aspartate (NMDA) receptor positron emission tomography (PET) ligands. The affinity of the different compounds was determined using in vitro receptor binding assays, and their log P values were estimated using HPLC analysis. The effect of N'-3 and N'-3,5 substitution on affinity and lipophilicity was examined. The K(i) values ranged from 1.87 to 839nM, while log P values between 1.22 and 2.88 were observed.

Overexpression of arginase alters circulating and tissue amino acids and guanidino compounds and affects neuromotor behavior in mice.

Arginine is an intermediate of the ornithine cycle and serves as a precursor for the synthesis of nitric oxide, creatine, agmatine and proteins. It is considered to be a conditionally essential amino acid because endogenous synthesis only barely meets daily requirements. In rapidly growing suckling neonates, endogenous arginine biosynthesis is crucial to compensate for the insufficient supply of arginine via the milk. Evidence is accumulating that the intestine rather than the kidney plays a major role in arginine synthesis in this period. Accordingly, ectopic expression of hepatic arginase in murine enterocytes by genetic modification induces a selective arginine deficiency. The ensuing phenotype, whose severity correlates with the level of transgene expression in the enterocytes, could be reversed with arginine supplementation. We analyzed the effect of arginine deficiency on guanidine metabolism and neuromotor behavior. Arginine-deficient transgenic mice continued to suffer from an arginine deficiency after the arginine biosynthetic enzymes had disappeared from the enterocytes. Postweaning catch-up growth in arginine-deficient mice was characterized by increased levels of all measured amino acids except arginine. Furthermore, plasma total amino acid concentration, including arginine, was significantly lower in adult male than in adult female transgenic mice. Decreases in the concentration of plasma and tissue arginine led to significant decreases in most metabolites of arginine. However, the accumulation of the toxic guanidino compounds, guanidinosuccinic acid and methylguanidine, corresponded inversely with circulating arginine concentration, possibly reflecting a higher oxidative stress under hypoargininemic conditions. In addition, hypoargininemia was associated with disturbed neuromotor behavior, although brain levels of toxic guanidino compounds and ammonia were normal.

Monocharged inhibitors of mast cell tryptase derived from potent and selective dibasic inhibitors.

Truncation of potent and selective dibasic inhibitors afforded monocharged inhibitors of human mast-cell tryptase. Using two classes of analogues as lead structures, several monocharged derivatives were identified with K(i) values ranging from 0.084 to 0.21 microM against the enzyme.

Magnesium lithospermate B suppresses the increase of active oxygen in rats after subtotal nephrectomy.

Subtotally nephrectomized rats were found to have decreased activities of superoxide dismutase (SOD) and catalase, and spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) showed that the amount of hydroxyl radical in the residual kidney tissue was greater than that in normal rat kidney. This indicated both direct and indirect involvement of free radicals in renal failure. In contrast, rats given magnesium lithospermate B (10 mg/kg body weight) orally for 30 days after subtotal nephrectomy showed restoration of SOD and catalase activities to almost normal levels. Hydroxyl radical, which is highly reactive and for which there is no scavenger system in the body, was decreased markedly in kidney homogenates obtained from rats given magnesium lithospermate B and in an experimental system for hydroxyl radical production to which magnesium lithospermate B was directly added. The increased levels of uremic toxins in the blood were also low in rats given magnesium lithospermate B. This indicates that magnesium lithospermate B helps to inhibit the progression of renal failure by scavenging radicals.