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Background Serum chloride derangements are associated with poor clinical outcomes, including acute kidney injury (AKI) and mortality. We sought to determine the association between persistent hyperchloremia and renal recovery in critically ill children with AKI. Methods We performed a retrospective cohort study of all patients with day 2 AKI admitted to a large academic pediatric intensive care unit from January 2014 to December 2015. After applying exclusion criteria, 348 patients were categorized as (1) hyperchloremia on both day 2 and day 7 (PersistentCl), (2) hyperchloremia on day 2 with normochloremia on day 7 (RecoveredCl), (3) normochloremia on day 2 with hyperchloremia on day 7 (DelayedCl), and (4) no hyperchloremia on day 2 nor day 7 (NormalCl). Hyperchloremia was defined as [greater than or equal to] 110 mEq/L. The primary outcome was renal recovery on day 7, defined as the absence of AKI criteria. Secondary outcomes included discharge renal recovery, mortality, duration of mechanical ventilation, and hospital length of stay. Results Day 7 renal recovery rates for PersistentCl, RecoveredCl, DelayedCl, and NormalCl were 37%, 66%, 71%, and 52% respectively. PersistentCl had lower odds of day 7 renal recovery (aOR = 0.29; 95% CI, 0.14 to 0.60; p = 0.0009), lower odds of discharge renal recovery (aOR = 0.22; 95% CI, 0.11 to 0.48; p = 0.0001), and higher odds of mortality (aOR = 3.50; 95% CI, 1.11 to 11.10; p = 0.03) when compared with RecoveredCl after adjusting for confounders. Conclusions Persistent hyperchloremia is independently associated with impaired renal recovery as well as higher mortality. Prospective studies are indicated to determine if serum chloride represents a modifiable risk factor for poor outcomes., Author(s): Matthew F. Barhight [sup.1] , John T. Brinton [sup.2] , Danielle E. Soranno [sup.3] [sup.4] , Sarah Faubel [sup.4] , Peter M. Mourani [sup.5] , Katja M. Gist [sup.6] [...]

Intravenous 0.9% saline has saved countless lives since it was introduced over a century ago. It remains the most widespread crystalloid in both adult and pediatric practice. However, in recent years, evidence of deleterious effects is accruing. These include increased mortality, acute kidney injury (AKI), metabolic acidosis, and coagulopathy. The predominant cause for these sequelae appears to be the excess chloride concentration of 0.9% saline relative to plasma. This has led to development of balanced isotonic solutions such as PlasmaLyte. This review summarizes current evidence for adverse effects of chloride-rich intravenous fluid and considers whether 0.9% saline should still be used in 2018 or abandoned as a historical treatment in favor of balanced crystalloid solutions., Author(s): Wesley Hayes [sup.1] [sup.2] Author Affiliations: (Aff1) grid.420468.c, Great Ormond Street Hospital, , London, UK (Aff2) 0000000121901201, grid.83440.3b, University College London Institute of Child Health, , London, UK Introduction [...]

The aim of this study was to investigate the hepatoprotective role of azadirachtin-A in carbon tetrachloride (C[Cl.s ub.4]) induced hepatotoxicity in rats. The group allotment for the animals used in the hepatoprotective study included a vehicle treatment group, C[Cl.sub.4] [(1 mL x (kg body mass).sup.-1]) treatment group, silymarin (100 µg x [(kg body mass).sup.-1] x [day.sup.-1]) + C[Cl.sub.4] treatment group, and groups treated with different doses of azadirachtin-A (100 or 200 µg x [(kg body mass).sup.-1] x [day.sup.-1]) + C[Cl.sub.4]. On the 9th day, blood was obtained for measuring the biochemical parameters, and liver tissue was obtained for pathological examination. The acute toxicity test with azadirachtin-A (500, 1000, or 2000 µg x [(kg body mass).sup.-1]) indicated no mortality after 14 days of treatment; further, there was no change in behavior, food consumption, or organ mass. However with the higher dose, some hematological parameters showed changes. Hepatoprotective studies revealed that the C[Cl.sub.4] treatment group exhibited a decrease in total protein and albumin levels, whereas a significant increase in BUN, AST, ALT, and ALP levels were noticed compared with the vehicle-treated control, indicating that there was liver damage caused by C[Cl.sub.4]. Histology and ultrastructure study confirmed that pretreatment with azadirachtin-A dose-dependently reduced hepatocellular necrosis and, therefore, protected the liver against toxicity caused by C[Cl.sub.4]. The results from this study indicate that pretreatment with azadirachtin-A at the higher dose levels, moderately restores the rat liver to normal. This study confirms that azadirachtin-A possesses greater hepatoprotective action; however, the effective concentration needs to be determined. Key words: azadirachtin-A, acute toxicity, C[Cl.sub.4], hepatoprotection, silymarin, rat. But de l'etude etait d'examiner le role hepatoprotecteur de azadirachtin-A, le tetrachlorure de carbone (C[Cl.sub.4]) hepatotoxicite chez les rats. Attribution de groupe dans l'etude hepatoprotective inclus vehicule, C[Cl.sub.4] (1 mL x [(kg de masse corporelle).sup.-1]), silymarine (100 ug x [(kg body mass).sup.-1]-jour-1) C[Cl.sub.4] et des doses progressives de azadirachtin-A (100 et 200 µg x [(kg body mass).sup.-1] x [jour.sup.-1]) C[Cl.sub.4]. Le 9eme jour, le sang a ete obtenu pour la determination des parametres biochimiques et les tissus du foie pour examen anatomo-pathologique. Toxicite aigue indique l'absence de mortalite apres 14 jours de traitement; plus il n'y a pas de changement dans son comportement, la consommation alimentaire et le poids des organes. Cependant, certains parametres hematologiques ont montre des alterations de leur valeur au niveau de dose superieur. Hepatoprotecteurs etudes ont revele que C[Cl.sub.4] groupe presentaient une diminution des taux de proteines totales et de l'albumine ou une augmentation significative de BUN, AST, ALT niveaux et ALP ont ete constatees par rapport a la maitrise du vehicule indiquant des dommages au foie causes par C[Cl.sub.4]. Histologie et l'etude de l'ultrastructure confirment que la dose pre-administration depend de azadirachtin-A reduit la necrose hepatocellulaire et donc proteger le foie contre la toxicite causee par C[Cl.sub.4]. Les resultats actuels indiquent que le pretraitement avec azadirachtin-A aux doses les plus elevees, moderement recuperer vers la normalisation dans le foie de rat. Cette etude confirme que azadirachtin-A possede une action rape hepatoprotective cependant, la concentration efficace appropriee doit etre fixe. Mots-cles: azadirachtin-A, la toxicite aigue, C[Cl.sub.4], hepatoprotection, silymarine, rat., Introduction In spite of tremendous advances in modern medicine, there are hardly any drugs that stimulate liver function, protect the liver from damage, or help to regenerate hepatic cells (Chaterjee [...]

This study investigated the effect of penehyclidine hydrochloride (PHC) on regulatory mediators during the neuroinflammatory response and cerebral cell apoptosis following cardiopulmonary bypass (CPB). Forty-eight rats were randomly divided among 4 groups as follows: sham-operation, vehicle, low-dose PHC (0.6 mg x [(kg body mass).sup.-1]), and high-dose PHC (2.0 x [(kg body mass).sup.-1]). CPB was performed in the latter 3 groups. The plasma levels of neuron specific enolase (NSE) and S-100B were tested with ELISA. Real-time PCR and Western blotting were used to evaluate the expression levels of matrix metalloproteinase-9 (MMP-9), IL-10, caspase-3, Bcl-2, and p38 in brain tissue. The ultrastructure of hippocampus tissue was examined under an electron microscope. PHC attenuated the increase of plasma NSE and S-100B following CPB. MMP-9, cleaved caspase-3, and phosphorylated p38 expression were substantially increased in the vehicle group compared with the shamoperation group and gradually diminished with increasing doses of PHC. IL-10 and Bcl-2 expression were markedly lower in the vehicle group than in the sham-operation group and gradually recovered with increasing doses of PHC. PHC attenuated the histopathological changes of cerebral injury following CPB. PHC favorably regulates the inflammatory response and reduces markers of neuronal injury following CPB, potentially by reducing p38 and caspase-3 activation. Key words: penehyclidine hydrochloride, cardiopulmonary bypass, cerebral injury. Cette etude a examine l'effet du chlorhydrate de penehyclidine (CPC) sur les mediateurs regulateurs lors de la reponse neuroinflammatoire et l'apoptose des cellules cerebrales qui suivent une derivation cardio-pulmonaire (DCP). Quarante-huit rats ont ete distribues au hasard en quatre groupes : fausse operation, vehicule, CPC a faible dose (0,6 mg x [([kg de poids corporel).sup.-1]) et CPC a forte dose (2,0 mg x [kg.sup.-1]). La DCP a ete realisee chez les trois derniers groupes. Les niveaux plasmatiques d'enolase specifique des neurones (NSE) et de S-100B ont ete mesures par ELISA. La PCR en temps reel et le buvardage Western ont ete utilises pour evaluer les niveaux d'expression de la metalloprotease matricielle 9 (MMP-9), de l'IL-10, de la caspase-3, de Bcl-2 et de p38 dans le tissu cerebral. L'ultrastructure de l'hippocampe a ete examinee par microscopie electronique. Le CPC attenuait l'augmentation des niveaux plasmatiques de NSE et de S-100B a la suite de la DCP. L'expression de la MMP-9, de la caspase-3 clivee et de la p38 phosphorylee etait accrue de maniere substantielle dans le groupe ayant recu le vehicule seul comparativement au groupe fausse operation, et elle diminuait graduellement en fonction de l'augmentation de la dose de CPC. L'expression de l'IL-10 et de Bcl-2 etait beaucoup plus faible dans le groupe ayant recu le vehicule comparativement au groupe fausse operation, et elle etait progressivement retablie en fonction de l'augmentation de la dose de CPC. Le CPC attenuait les changements histopathologiques lies au dommage cerebral suivant une DCP. Le CPC regule favorablement la reponse inflammatoire et reduit les marqueurs du dommage neuronal apres une DCP, possiblement par l'intermediaire de la reduction de l'activation de p38 et de la caspase-3. [Traduit par la Redaction] Mots-cles: chlorhydrate de penehyclidine, derivation cardio-pulmonaire, dommage cardiaque., Introduction Cardiopulmonary bypass (CPB) is an essential component of intracardiac surgical procedures during cardiac surgery. Patients who undergo CPB surgery are particularly prone to adverse cerebral outcomes, including stroke, hypoxic [...]

Salt reabsorption by the loop of Henle controls NaC1 handling and blood pressure regulation. Increased oxidative stress stimulates NaC1 transport in one specific segment of the loop of Henle called the thick ascending limb (TAL). The isoprostane 8-iso-prostaglandin-F2[alpha] (8iso-PGF2[alpha]) is one of the most abundant nonenzymatic lipid oxidation products and has been implicated in the development of hypertension. However, it is not known whether 8-iso-PGF2[alpha] regulates transport or the mechanisms involved. Because protein kinase A (PKA) stimulates NaCI transport in several nephron segments, we hypothesized that 8-iso-PGF2[alpha] increases NaC1 transport in the cortical TAL (cTAL) via a PKA-dependent mechanism. We examined the effect of luminal 8-iso-PGF2[alpha] on NaC1 transport by measuring chloride absorption ([J.sub.C1]) in isolated microperfused cTALs. Adding 8-iso-PGF2[alpha] to the lumen increased [J.sub.CI] by 54% (from 288.7 [+ or -] 30.6 to 446.5 [+ or -] 44.3 pmol x [min.sup.-1] x [mm.sup.-1]; P < 0.01), while adding it to the bath enhanced [J.sub.C1] by 35% (from 236.3 [+ or -] 35.3 to 319.2 [+ or -] 39.8 pmol x [min.sup.-1] x [mm.sup.-1]; P < 0.05). This stimulation was blocked by Na-K-2C1 cotransporter inhibition. Next, we tested the role of cAMP. Basal cAMP in the cTAL was 18.6 [+ or -] 1.6 fmol x [min.sup.-1] x [mm.sup.-1], and 8-iso-PGF2[alpha] raised it to 35.1 [+ or -] 1.4 fmol x [min.sup.-1] x [mm.sup.-1], an increase of 94% (P < 0.01). Because cAMP stimulates PKA, we measured [J.sub.C1] using the PKA-selective inhibitor H89. In the presence of H89 (10 [micro]M), 8-iso-PGF2[alpha] failed to increase transport regardless of whether it was added to the lumen (216.1 [+ or -] 16.7 vs. 209.7 [+ or -] 23.8 pmol x [min.sup.-1] x [mm.sup.-1]; NS) or the bath (150.4 [+ or -] 32.9 vs. 127.1 [+ or -] 28.6 pmol x [min.sup.-1] x [mm.sup.-1]; NS). We concluded that 8-iso-PGF2[alpha] stimulates cAMP and increases C1 transport in cTALs via a PKA-dependent mechanism. salt reabsorption; cortico-medullary osmotic gradient doi: 10.1152/ajprenal.00225.2010

Neuropeptide Y (NPY), an important proabsorptive hormone of the gastrointestinal tract has been shown to inhibit chloride secretion and stimulate NaCl absorption. However, mechanisms underlying the proabsorptive effects of NPY are not fully understood. The present studies were designed to examine the direct effects of NPY on apical [Cl.sup.-]/H[CO.sup.-.sub.3](O[H.sup.-]) exchange activity and the underlying mechanisms involved utilizing Caco2 cells. Our results showed that NPY (100 nM, 30 min) significantly increased [Cl.sup.-]/H[CO.sup.-.sub.3](O[H.sup.-]) exchange activity (~2-fold). Selective NPY/Y1 or Y2 receptor agonists mimicked the effects of NPY. NPY-mediated stimulation of [Cl.sup.-]/H[CO.sup.-.sub.3](O[H.sup.-]) exchange activity involved the ERK1/2 MAP kinase-dependent pathway. Cell surface biotinylation studies showed that NPY does not alter DRA (apical [Cl.sup.-]/H[CO.sup.-.sub.3](O[H.sup.-]) exchanger) surface expression, ruling out the involvement of membrane trafficking events. Interestingly, DRA was found to be predominantly expressed in the detergent-insoluble (DI) and low-density fractions (LDF) of human colonic apical membrane vesicles (AMVs) representing lipid rafts. Depletion of membrane cholesterol by methyl-[beta]-cyclodextrin (M[beta]CD, 10 mM, 1 h) remarkably decreased DRA expression in the DI fractions. Similar results were obtained in Triton-X 100-treated Caco2 plasma membranes. DRA association with lipid rafts in the DI and LDF fractions of Caco2 cells was significantly enhanced (~45%) by NPY compared with control. M[beta]CD significantly decreased [Cl.sup.-]/H[CO.sup.-.sub.3](O[H.sup.-]) exchange activity in Caco2 cells as measured by DIDS- or niflumic acid-sensitive [sup.36][Cl.sup.-] uptake (~50%). Our results demonstrate that NPY modulates [Cl.sup.-]/ H[CO.sup.-.sub.3](O[H.sup.-]) exchange activity by enhancing the association of DRA with lipid rafts, thereby resulting in an increase in [Cl.sup.-]/ H[CO.sup.-.sub.3](O[H.sup.-]) exchange activity. Our findings suggest that the alteration in the association of DRA with lipid rafts may contribute to the proabsorptive effects of NPY in the human intestine. chloride absorption; human intestine; downregulated in adenoma; ERK 1/2 MAP kinase doi: 10.1152/ajpgi.00039.2010.

BACKGROUND: Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is [...]

Chloride homeostasis in Saccharomyces cerevisiae has been characterized with the goal of identifying new [Cl.sup.-] transport and regulatory pathways. Steady-state cellular [Cl.sup.-] contents (~0.2 mEq/liter cell water) differ by less than threefold in yeast grown in media containing 0.003-5 inM [Cl.sup.-]. Therefore, yeast have a potent mechanism for maintaining constant cellular [Cl.sup.-] over a wide range of extracellular [Cl.sup.-]. The cell water:medium [[Cl.sup.-]] ratio is >20 in media containing 0.01 mM [Cl.sup.-] and results in part from sequestration of [Cl.sup.-] in organelles, as shown by the effect of deleting genes involved in vacuolar acidification. Organellar sequestration cannot account entirely for the [Cl.sup.-] accumulation, however, because the cell water:medium [[Cl.sup.-]] ratio in low [Cl.sup.-] medium is ~10 at extracellular pH 4.0 even in vmal yeast, which lack the vacuolar [H.sup.+]-ATPase. Cellular [Cl.sup.-] accumulation is ATP dependent in both wild type and vmal strains. The initial [sup.36][Cl.sup.-] influx is a saturable function of extracellular [[sup.36][Cl.sup.-]] with [K.sub.1/2] of 0.02 mM at pH 4.0 and >0.2 mM at pH 7, indicating the presence of a high affinity [Cl.sup.-] transporter in the plasma membrane. The transporter can exchange [sup.36][Cl.sup.-] for either [Cl.sup.-] or [Br.sup.-] far more rapidly than S[O.sub.4] , phosphate, formate, HC[O.sub.3.sup.-] , or N[O.sub.3.sup.-] . High affinity [Cl.sup.-] influx is not affected by deletion of any of several genes for possible [Cl.sup.-] transporters. The high affinity [Cl.sup.-] transporter is activated over a period of ~45 min after shifting cells from high-[Cl.sup.-] to low-[Cl.sup.-] media. Deletion of ORFYHL008c (formate-nitrite transporter family) strongly reduces the rate of activation of the flux. Therefore, Yhl008cp may be part of a [Cl.sup.-]-sensing mechanism that activates the high affinity transporter in a low [Cl.sup.-] medium. This is the first example of a biological system that can regulate cellular [Cl.sup.-] at concentrations far below 1 mM.

Active [Na.sup.+] absorption across rumen epithelium comprises [Na.sup.+]/[H.sup.+] exchange and a nonselective cation conductance (NSCC). Luminal chloride is able to stimulate [Na.sup.+] absorption, which has been attributed to an interaction between [Cl.sup.-]/HC[O.sup.-.sub.3] and [Na.sup.+]/[H.sup.+] exchangers. However, isolated rumen epithelial cells also express a [Cl.sup.-] conductance. We investigated whether [Cl.sup.-] has an additional effect on electrogenic [Na.sup.+] absorption via NSCC. NSCC was estimated from short-circuit current ([I.sub.sc]) across epithelia of goat and sheep rumen in Ussing chambers. Epithelial surface pH (p[H.sub.s]) was measured with 5-N-hexadecanoyl-aminofluorescence. Membrane potentials were measured with microelelectrodes. Luminal, but not serosal, [Cl.sup.-] stimulated the [Ca.sup.2+] and [Mg.sup.2+] sensitive [I.sub.sc]. This effect was independent of the replacing anion (gluconate or acetate) and of the presence of bicarbonate. The mean pHs of rumen epithelium amounted to 7.47 [+ or -] 0.03 in a low-[Cl.sup.-] solution. It was increased by 0.21 pH units when luminal [Cl.sup.-] was increased from 10 to 68 mM. Increasing mucosal pH from 7.5 to 8.0 also increased the [Ca.sup.2+] and [Mg.sup.2+] sensitive [I.sup.sc] and transepithelial conductance and reduced the fractional resistance of the apical membrane. Luminal [Cl.sup.-] depolarized the apical membrane of rumen epithelium. 5-Nitro-2-(3-phenylpropylamino)-benzoate reduced the divalent cation sensitive [I.sub.sc], but only in low-[Cl.sup.-] solutions. The results show that luminal [Cl.sup.-] can increase the microclimate pH via apical [Cl.sup.-]/HC[O.sup.-.sub.3] or [Cl.sup.-]/O[H.sup.-] exchangers. Electrogenic [Na.sup.+] absorption via NSCC increases with pH, explaining part of the [Cl.sup.-] effects on [Na.sup.+] absorption. The data further show that the [Cl.sup.-] conductance of rumen epithelium must be located at the basolateral membrane. electrolyte transport; sodium absorption; forestomach; ruminants; microclimate doi:10.1152/ajpgi.00419.2005

Byline: F. Schier (1), M. Bondartschuk (1), E. Danzer (1) Keywords: Keywords Tetrachlorodecaoxide; Intra-abdominal adhesions Abstract: Tetrachlorodecaoxide (TCDO) is a negatively-charged complex of chlorine and oxygen commonly used for the treatment of infected external wounds. However, it displays antiadhesive properties when applied intra-abdominally. In rats, small-bowel and a large-bowel anastomoses were performed and one-half of the animals received TCDO. It was found that TCDO did not alter the bursting pressures of small and large-bowel anastomoses at 1, 3 and 9 days postoperatively. Author Affiliation: (1) Department of Pediatric Surgery, University Medical Center Jena, Bachstrasse 18, 07740 Jena, Germany, DE Article note: Accepted: 12 May 2000

This study was undertaken to determine the occurrence, fate and origin of 1,2-dichloropropane in water samples from a shallow aquifer that has different redox zones with an overlay of intensive agricultural activity. The study was conducted by the U.S. Geological Survey, the School of Civil and Environmental Engineering, Georgia Institute of Technology and Environment Canada.

Byline: M. Hayhoe (1), R. Bellomo (1), G. Liu (2), L. McNicol (2), B. Buxton (3) Keywords: Key words Metabolic acidosis; Cardiopulmonary bypass; Polygeline; Chloride; Cardiac surgery; Lactate Abstract: Objective: The pathogenesis of the metabolic acidosis of cardiopulmonary bypass (CPB) is not fully understood. New quantitative methods of acid-base balance now make it possible to describe it more clearly. Accordingly, we studied acid-base changes during CPB with polygeline pump prime and defined and quantified the factors which contribute to metabolic acidosis. Design: Prospective cohort study. Setting: Tertiary institution. Participants: 10 cardiac bypass graft surgery patients. Interventions: Sampling of arterial blood at four time intervals: post-induction, on CPB during cooling and rewarming, and at skin closure. Measurement of serum Na.sup.+, K.sup.+, Mg.sup.+ +, Ca.sup.+ +, Cl.sup.--, bicarbonate, and phosphate concentrations, arterial blood gases, and serum albumin, lactate, and pyruvate concentrations at each collection point. Analysis of findings according to quantitative physicochemical principles, including calculation of the strong ion difference apparent, the strong ion difference effective, and the strong ion gap (SIG). Measurements and main results: All patients developed a mild metabolic acidosis. The median serum standard bicarbonate concentration decreased from 25.0 mEq/l post-induction to 22.3 mEq/l at cooling and 22.2 mEq/l at rewarming (p < 0.05). The standard base excess decreased from a median of 1.55 mEq/l prior to CPB, to --2.50 mEq/l at cooling, --1.65 mEq/l at rewarming and, --0.85 mEq/l at skin closure (p < 0.001). This mild metabolic acidosis occurred despite a decrease in the median serum lactate concentration from 3.20 mEq/l post-induction to 1.83, 1.80, and 1.58 mEq/l at the three other time points. The increase in the median serum chloride concentration from 104.9 mEq/l post induction to 111.0, 111.1, and 110.0 mEq/l at the subsequent time points (p < 0.0001) was the main cause of the acidosis. There was also a significant increase in the SIG of 3.8 mEq/l at cooling and rewarming (p < 0.0001), suggesting a role for other unmeasured anions (polygeline) in the genesis of this acidosis. Conclusions: Using quantitative biophysical methods, it can be demonstrated that, in patients receiving a pump prime rich in chloride and polygeline, the metabolic acidosis of CPB is mostly due to iatrogenic increases in serum chloride concentration and unmeasured strong anions (SIG). Its development is partially attenuated by iatrogenic hypoalbuminaemia. Changes in lactate concentrations did not play a role in the development of metabolic acidosis in our patients. Author Affiliation: (1) Intensive Care Unit, Department of Intensive Care Medicine, Austin and Repatriation Medical Centre, Heidelberg Vic 3084, Australia Tel.: + 61 (3) 9496--5992 Fax: + 61 (3) 9496--3932 email: rb@austin.unimelb.edu.au, AU (2) Department of Anaesthesia, Austin and Repatriation Medical Centre, Heidelberg Vic 3084, Australia, AU (3) Department of Cardiac Surgery, Austin and Repatriation Medical Centre, Heidelberg Vic 3084, Australia, AU Article note: Received: 21 October 1998 Final revision received: 16 March 1999 Accepted: 26 March 1999

1,2-Dichloropropane (DCP) is toxic to mammals when ingested or inhaled. DCP poisoning in humans is frequent in Italy where DCP is commonly used in commercial solvents and dry cleaners. DCP causes liver toxicity and may also affect the heart, kidneys and the central nervous system. However, the mechanism underlying this toxicity is unknown. A study was performed to determine the mechanism of DCP toxicity. The body can detoxify compounds by attaching glutathione (GSH) to the compound, which allows the compound to be excreted in urine. When rats were given oral doses of DCP there was a dramatic decrease in tissue and serum GSH levels. Administration of a chemical which depletes GSH (buthionine-sulfoximine, BSO) significantly increased mortality in DCP-treated rats compared with rats receiving DCP alone. On the other hand, rats treated with a GSH precursor (N-acetylcysteine, NAC) to increase GSH levels, were protected from DCP toxicity. These results indicate that DCP toxicity is a result of GSH depletion and that drugs which increase GSH levels, such as NAC, may be useful in treating DCP poisoning in humans. (Consumer Summary produced by Reliance Medical Information, Inc.)

Author(s): Uwe Querfeld [sup.1] , Silvia Lechner [sup.2] , Andreas R. Janecke [sup.3] Author Affiliations: (1) grid.6363.0, 0000 0001 2218 4662, Department of Pediatric Nephrology, Charité Berlin, , Augustenburger Platz [...]