bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aluminium deposition in liver and kidney following acute intravenous administration of aluminium chloride or citrate in conscious rats
Authors: Spencer AJ , Wood JA , Saunders HC , Freeman MS , Lote CJ 
Published: December 2008

1 Plasma, urinary, liver and kidney cell aluminium (Al) levels were monitored in the rat, 1h after intravenous administration of 29630 nmol (800 μg) Al as either Al chloride or as Al citrate (Al chloride plus excess sodium citrate). Al levels were measured in plasma, urine and liver by atomic absorption spectroscopy (AAS). Liver and kidney Al content was measured at the cellular and subcellular level by electron probe X-ray microanalysis (EPXMA).2 Urinary excretion of Al was significantly higher ( P < 0.01), when Al was given as the citrate than as the chloride. After 1h, plasma Al levels were significantly lower in the Al citrate group than the Al chloride group (59 ± 3.7 vs 877 ± 214 nmol ml-1, respectively; P< 0.01).3 Al concentrations were significantly higher in the livers of rats receiving Al chloride (818 ± 252 nmol g-1wet weight; P < 0.05), than in either control or Al citrate groups (122 ± 41 and 107 ± 26 nmol g-1wet weight, respectively). Al concentrations derived from EPXMA measurements were in agreement with AAS values for the three groups, with significantly higher Al concentra tions in the Al chloride group (1.7 ± 0.4 nmol mg-1dry weight; P < 0.05) than in the control or Al citrate groups, where Al was not detectable. EPXMA analysis showed that Al was distributed in all liver organelles analysed (cytoplasm, mitochondria, nucleus, ER) and was not preferentially taken up by any one organelle in Al chloride treated rats.4 Significant amounts of Al were found in cytoplasm and mitochondria of proximal tubule cells of rats given Al citrate (0.64 ± 0.15 and 0.80 ± 0.11 nmol mg-1dry weight, respectively), but not in nuclei or lysosomes of these cells. Al levels were not detectable in control kid neys, in proximal tubule cells after Al chloride adminis tration or distal tubule cells after either Al treatment.
Effect of urinary alkalinisation and acidification on the tissue distribution of hexachlorophene in rats
Authors: Flanagan RJ , Ruprah M. , Strutt AV , Malarkey P. , Cockburn A. 
Published: December 2008

1 Urinary alkalinisation may be helpful in treating acute poisoning with uncouplers of oxidative phosphorylation containing a phenolic hydroxyl (pKa 4-6) or other acidic moiety. 2 We studied the effects of urine alkalinisation and acidi fication on the tissue distribution of hexachlorophene (HCP, pKa 5.7) in male Sprague Dawley rats (10 rats/group). 3 Ammonium chloride (10 mL kg-1, 2% m/v) or sodium bicarbonate (10 mL kg-1, 2% m/v) were administered by gavage on three occasions over 24 h, prior to a single gavage dose of HCP (180 mg kg-1). Controls received aqueous sodium chloride (10 mL kg-1, 0.9% m/v) fol lowed by either HCP (180 mg kg-1) or vehicle alone. 4 Urine pH, body mass and body temperature were moni tored during the study and, at the conclusion of the experiment (12 h post-HCP dose), organ mass (liver, kidney, brain), and plasma, urine and tissue HCP concentrations were measured. 5 No clinical features of toxicity were observed in any group. However, sodium bicarbonate significantly reduced median HCP in liver — median plasma and kidney HCP concentrations were also reduced but not significantly. Conversely, ammonium chloride signifi cantly increased median HCP concentrations in liver and kidney — median plasma HCP was also increased but not significantly. 6 The results provide some support for the hypothesis that blood pH influences the tissue distribution of uncou plers of oxidative phosphorylation containing an acidic moiety. Urinary alkalinisation may be useful in treating acute poisoning with these compounds.
Review : Neuropsychopathological changes by organophosphorus compounds — a review
Authors: Eyer P. 
Published: December 2008

1 Available literature dealing with neuropsychopathologi cal changes after exposure to organophosphate insecti cides is reviewed.2 Subacute neurological sequelae following acute organophosphate intoxication include the 'intermediate syndrome', probably a myopathy elicited by excess acetylcholine, and the 'organophosphate-induced delayed neuropathy' (OPIDN), which is caused by particularly neurotoxic organophosphates that inhibit neuropathy target esterase.3 Long-term toxic effects affecting behaviour as well as mental and visual functions are occasionally observed after exposure to high doses of organophosphates with repeated acute, clinically significant intoxications.4 The available data do not indicate that asymptomatic exposure to organophosphates is connected with an increasing risk of delayed or permanent neuro psychopathological effects.
Immunotoxicity study of repeated small doses of dimethoate and methylparathion administered to rats over three generations
Authors: Institóris L. , Siroki Olga , Dési I. 
Published: December 2008

Immunotoxic effects of chronic, equitoxic doses (1/50, 1/75, and 1/100 LD50) of two organophosphorus pesticides dimethoate (DM) and methylparathion (MPT) (14.1, 9.39, and 7.04 mg kg-1DM; and 0.436, 0.291, and 0.218 mg kg-1MPT) were investigated in a three generation study in out- bred Wistar rats. Treatment of the first generation (G1) with these doses began in animals 4 weeks of age; the parental males were dosed until separation of females, and after mating the females were treated until separation of their G2 offspring (at the age of 4 weeks), and the G3 generation was produced in the same way from treated parental G2 animals. Selected 4 week old males from each generation were also treated with DM and MPT for 4 weeks (experimental groups) before determination of certain conventional toxicological (body weight gain, birth weight and number, organ weights), haematological (absolute and differential WBC, RBC, Ht, MCV, nucleated cell content of femoral bone marrow), and immune func tion parameters (IgM-PFC number of spleen, DTH reac tion).Effects of both substances on immunological variables were detectable at the 1/75 LD50 dose level, but different parameters were affected in the three consecutive genera tions.
Effects of fish oil and sunflower oil supplementations on gentamicin-induced nephrotoxicity in rat
Authors: Abdel-Gayoum AA , Bashir AA , El-Fakhri MM 
Published: December 2008

1 Nephrotoxicity was induced in rats by intramuscular administration of gentamicin (80 mg kg-1d-1) for 6 days.2 Oral supplementation with fish oil (5 ml kg-1d-1), for 2 weeks prior to and during gentamicin exposure, markedly ameliorated the drug-induced nephrotoxici ty. The beneficial effects of oil were evidenced by sig nificantly reduced serum creatinine and urea concen trations, increased renal cortical alkaline phosphatase activity and improved renal tubular histology, com pared with the non oil-treated animals, receiving gen tamicin.3 Similar supplementation with sunflower oil, rich in ω-6 fatty acids, failed to reverse any of the parameters of nephrotoxicity induced by gentamicin.4 Hypercholesterolaemia and reduced cortical GSH associated with gentamicin nephrotoxicity were both normalised by supplementation with fish oil, but not by sunflower oil.5 The beneficial effects of fish oil on gentamicin-induced nephrotoxicity were not related to the extent of uptake and accumulation of the drug by the kidney.
Optimising the removal of inhaled plutonium and americium from the rat by administration of ZnDTPA in drinking water
Authors: Gray SA , Pearce MJ , Stradling GN , Wilson I. , Hodgson A. , Isaacs KR 
Published: December 2008

1 The efficacy of ZnDTPA administered in drinking water has been investigated for removing 238 Pu and 241Am from the rat after their simultaneous inhalation as nitrates. 2 The continual administration of ZnDTPA 95 μmol kg-1 d-1 over a 21 d interval commencing 1 h after exposure reduced the 238Pu content of the lungs and total body to 2% and 8% of those in untreated animals; the corresponding values for 241Am were 3% and 5%. 3 The continual intakes of 950 μmol kg-1 d-1, intermittent intakes of 3600 μmol kg-1 d-1 and the repeated injection of 30 μmol kg-1 body weight were considered no more effective. 4 All orally administered concentrations of ZnDTPA, commencing 7 d after exposure, reduced the total body contents of 238Pu and 241Am to 17% and 20% of controls by 28 d. 5 Histopathological examination of the kidneys, liver and gastrointestinal tract showed no apparent effects of these treatment protocols. 6 It is concluded that the oral administration of ZnDTPA could be an effective treatment for the removal of inhaled transportable forms of Pu and Am after human exposure.
Comparison of the efficacy of HI-6 and obidoxime against cyclohexyl methyl phosphonofluoridate (GF) in rats
Authors: Kassa J. , Bajgar J. 
Published: December 2008

1 The efficacy of HI-6 and obidoxime in combination with atropine on cyclohexyl methylphosphonofluoridate (GF)- induced cholinergic and stressogenic effects in rats was studied. 2 HI-6 sufficiently reactivated cholinesterase activity in blood as well as acetylcholinesterase activity in brain and diaphragm following GF intoxication, and practically eliminated stressogenic effects of GF (an increase in plas ma corticosterone level and liver tyrosine aminotrans ferase activity). 3 Obidoxime had practically no effect on enzyme activity or stressogenic effects of GF agent. 4 These findings confirm that HI-6 has definite advan tages over obidoxime in the treatment of intoxication with GF.
Renal excretion of aluminium in the rat: effect of citrate infusion
Authors: Lote CJ , Willmott K. , Wood Jeanne A , Thewles A. , Freeman M. 
Published: December 2008

When aluminium is administered intravenously to rats, the speciation of the aluminium has a major effect on its renal excretion. Aluminium administered as citrate is much more effectively excreted than that administered as chloride or sulphate. This suggests that citrate could be therapeutically useful in patients who have been exposed to aluminium. Accordingly, we have performed two series of experi ments in rats, in which a citrate infusion (intravenous), was begun either immediately after, or one hour after, the administration of an intravenous aluminium sulphate bolus. Both protocols led to markedly enhanced alumini um excretion compared to controls in which only 0.7% NaCl was infused. The enhancement of aluminium excre tion was 783% if citrate infusion was begun immediately after aluminium administration, and 335% if the citrate infusion began after an hour delay. The increased excre tion was due to an increase in the freely filterable fraction of aluminium. In the control experiments, in which aluminium sul phate administration was followed by 0.7% NaCl infusion, aluminium was found to be deposited in the liver. Administration of citrate one hour after the aluminium bolus did not reduce this liver deposition. The results indicate that a fraction of the plasma alu minium is accessible to the citrate infused and can thereby be converted into a filterable form which can be excreted. It appears that, for maximum therapeutic effect, citrate should be infused as rapidly as possible after an alumini um load, to limit aluminium binding to ligands which allow it to enter cells.
Distribution of nickel in body fluids and organs of rats chronically exposed to nickel sulphate
Authors: Severa J. , Vyskocil A. , Fiala Z. , Cizkova M. 
Published: December 2008

1 Male and female rats were given 100 mg Ni L-1 (as nick el sulphate) in drinking water for 6 months. 2 The feeding of nickel was associated with an increased concentration of nickel in body fluids and organs. The highest concentrations of nickel were found in the liver of both male and female rats. In male rats nickel levels decreased in the order: liver > kidney = whole blood = serum > testes > urine. In female rats the decreasing order was similar: liver > kidney = whole blood = serum = plasma > urine > ovaries. 3 No significant differences were found between nickel concentrations in organs (except ovaries), blood and urine of rats exposed for 3 months and those exposed for 6 months indicating the reaching of a steady state of nickel in the rat during long-term exposure. 4 The urinary excretion of the orally administered nickel was only 2% of absorbed dose (supposing 1% Ni absorp tion).
Bolesatine induces agglutination of rat platelets and human erythrocytes and platelets in vitro
Authors: Gachet C. , Ennamany R. , Kretz O. , Ohlmann P. , Krause C. , Creppy EE , Dirheimer G. , Cazenave JP 
Published: December 2008

Bolesatine is a toxic glycoprotein isolated from the mushroom Boletus satanas Lenz, which has been shown to inhibit protein synthesis in cell-free systems and cell culture. It is toxic to rodents, the LD50% 24 h being 1 mg kg-1 (i.p.) and 0.15 mg kg-1 (i.v) in the rat in which it induces hepatic blood stasis. Bolesatine possesses lectinic properties with in parti cular a sugar binding site for D-galactose and mitogenic activity toward lymphocytes. Tested for cell agglutination on red blood cells and platelets, bolesatine agglutinates both human and rat platelets from threshold concentrations of 30 and 300 nM respectively. EDTA and PGI2 (aggregation inhibitors) do not decrease the agglutination induced by bolesatine, indicating that the process does not involve platelet activation. In contrast, fibrinogen decreases platelet agglutination in duced by bolesatine, most likely by masking the binding sites on platelets or by interacting with the toxin. Bolesatine agglutinates all red blood cells without any blood group specificity in the concentration range of 20 to 40 nM. This haemagglutination cannot be prevented by sugars, including D-galactose at a concentration of 0.5 M.
Some immunological parameters in workers occupationally exposed to n-hexane
Authors: Karakaya A. , Yücesoy B. , Burgaz S. , Sabir HU , Karakaya AE 
Published: December 2008

1 To estimate the quantitative relation between exposure to airborne n-hexane and various markers of immune function, 35 male workers were examined and compared with unexposed controls. 2 Urinary 2,5-hexanedione concentrations were signifi cantly higher in the exposed group than in the unexposed. 3 A significant suppression was observed in the serum immunoglobulin (IgG, IgM and IgA) levels between two populations. Also, a significant correlation was found between urinary 2,5-hexanedione concentrations and serum Ig level of the exposed group. 4 No significant difference between white blood cell counts was found in the two groups.
Transplacental passage of [3H]-okadaic acid in pregnant mice measured by radioactivity and high-performance liquid chromatography
Authors: Matias WG , Creppy EE 
Published: December 2008

Okadaic acid (OA) is the main toxin produced by dinoflagellates, which can accumulate in the hepatopan creas of mussels and cause diarrhoetic shellfish poisoning in consumers. This toxin is also a tumour promoter and a specific potent inhibitor of protein phosphatases 1 and 2A. The results in this study show for the first time that this marine toxin is able to cross the transplacental barrier. Foetal tissue contains more okadaic acid than the liver or kidney: 5.60% compared to 1.90 and 2.55% respectively as measured by HPLC and fluorescent detection after derivatization with 9-Anthryldiazomethane (ADAM). In view of its adverse effects, okadaic acid might impair foetal development and promote tumours in neonates.
Concentrations of trichloroethylene and its metabolites in blood and urine after acute poisoning by ingestion
Authors: Yoshida M. , Fukabori S. , Hara K. , Yuasa H. , Nakaaki K. , Yamamura Y. , Yoshida K. 
Published: December 2008

A 58-year-old man fell into a trichloroethylene reservoir bath head first, during a maintenance degreasing bath and accidentally ingested the solvent. Although he showed deep coma, chemical burns and pneumonia on admission, these symptoms gradually subsided. The concentrations of trichloroethylene (TRI) and its metabolites, trichloroethanol (TCE) and trichloroacetic acid (TCA) in blood and urine were measured during hospitalization. Eight hours after the accident, the concentrations ofTRI and its metabolites in serum were 31.4 μ g/ml TRI, 16.5 μg/ ml TCE and 79.5 μg/ml TCA. The serum TRI concentration decreased to 4.3 μg/ml on the following day. Elimination of TCE and TCA from serum occurred biphasically, the estimated half-lives of each metabolites being about 52.6 and 50.4 h in an initial fast phase and 268.3 and 277.2 h in a subsequent slow phase, respectively. Urinary TRI excretion persisted for the first 2 days. The urinary TCE and TCA excretions were longer than that of TRI with a biphasic decrease and the total amount of TCE excreted during the first 2 days was about two times that of TCA. The half-life of urinary TCE excretion (t½ 25.7 h) was shorter than that of TCA (t½ 52.1 h) in the fast phase but did no difference during the slow phase, with each half-time being about 166.3 h. The kinetics of TRI metabolites in blood and urine in this case were in slight agreement with the results following inhalation exposure previously reported in the literature.
Single fibre electromyographic changes in man after organophosphate exposure
Authors: Baker DJ , Sedgwick E Michael 
Published: December 2008

1 Neuromuscular (NM) changes resulting from organo phosphate exposure are known to be complex. After severe acute poisoning recovery from initial depolar isation paralysis may be followed in a limited number of cases by onset of a non-depolarisation paralysis (the Intermediate Syndrome). It is not clear whether this block arises subclinically in all cases of poisoning as a sequel to the initial depolarisation. 2 Single fibre electromyography (SFEMG) is a sensitive clinical neurophysiological technique allowing detec tion of subclinical changes at the neuromuscular junction. In the study reported it has been used to examine changes in NM transmission in the forearm of fit volunteers exposed to a low level of sarin (isopropyl methyl phosphonofluoridate). 3 Small changes in SFEMG were seen at three hours and three days after an exposure sufficient to cause a reduction in red cell acetyl cholinesterase to 60% of normal. The SFEMG changes were not accompanied by any clinical neuromuscular symptoms or signs and returned to normal 2 years after exposure. 4 The results indicate that there are reversible subclini cal changes compatible with the development of non depolarising NM block without frank clinical expres sion. In the small population examined there were individual variations in response which may reflect differences in safety margin at the neuromuscular junction.
The influence of pharmacological pretreatment on efficacy of HI-6 oxime in combination with benactyzine in soman poisoning in rats
Authors: Kassa Jiří , Bajgar Jiří 
Published: December 2008

1 The influence of pharmacological pretreatment (pyr idostigmine, benactyzine and trihexyphenidyle), de signated PANPAL, on soman-induced cholinergic and stressogenic effects as well as on the efficacy of antidotal treatment (HI-6 plus obidoxime) in rats was studied. 2 PANPAL prophylaxis significantly decreased soman- induced cholinesterase inhibition in blood, brain and diaphragm as well as stressogenic effects of soman (an increase in plasma corticosterone level and liver tyrosine aminotransferase activity). 3 PANPAL pretreatment did not improve the efficacy of HI-6 in combination with benactyzine on soman- induced anticholinesterase and stressogenic effects. 4 These findings confirm that PANPAL prophylaxis can improve prognosis of soman poisoning especially by protection of cholinesterases.
Cadmium-induced alterations in blood- brain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat
Authors: Shukla Arti , Shukla Girja S , Srimal RC 
Published: December 2008

1 Male albino rats of 21 days age were exposed to 10 p.p.m. cadmium (CdCl2 salt) in drinking water, ad libitum, for 90 days. It increased the brain cadmium levels by 76% ( P < 0.05) and 165% ( P < 0.001) respec tively at 30 and 90 days of exposure compared to controls. 2 Cadmium increased blood - brain barrier permeability of fluoroscein dye (24%, P < 0.02) and the levels ofbrain microvessel malondialdehyde (31%, P<0.01) at 90 days of exposure. However, these parameters did not alter significantly at 30 days of exposure. 3 Increased activities of microvessel superoxide dismu tase (18%, P<0.02), glutathione peroxidase (20%, P<0.01) and catalase (28%, P<0.01) were observed at 30 days of exposure. 4 The continuation of the Cd treatment for 90 days decreased the levels of superoxide dismutase (30%, P<0.001), glutathione peroxidase (23%, P<0.005), catalase (25%, P < 0.005), glutathione reductase (18%, P < 0.02), vitamin E (20%, P < 0.01), glutathione (26%, P < 0.01), ascorbic acid (18%, P < 0.05) and ceruloplas min (13%, P<0.05) in the microvessal preparation compared to controls. 5 It appears that Cd-induced blood-brian barrier dysfunction may be related to the depletion of microvessel antioxidant substances along with in crease in lipid peroxidation at 90 days of exposure.
Mitigation of nitrofurantoin-induced toxicity in the perfused rat liver
Authors: Wei Shen  , Hoener Betty-ann 
Published: December 2008

1 Nitrofurantoin is an antimicrobial agent which pro duces hepatotoxicity caused by the redox cycling of the nitro group and its radical anion. This futile cycling triggers a complex series of events known collectively as oxidative stress.2 Our goal was to determine treatment strategies which could mitigate nitrofurantoin-induced toxicity in the isolated perfused rat liver. We co-infused various agents which blocked early or late events in the progression to toxicity. Tissue levels of glutathione and protein thiols were measured as indicators of the progression to toxicity and lactate dehydrogenase leakage into the perfusate was used as a marker of irreversible cell death.3 Five treatments significantly ( P < 0.05) decreased LDH leakage (reported as thousands of units accumulated in perfusate at 300 min, mean ± standard error, n=3- 4) when compared to nitrofurantoin alone (274 ±37). These treatments were adenosine-2'-monophosphate (120 ± 53), penicillamine (90 ± 29), N-(2-mercaptopro pionyl)-glycine (120 ± 49) and bromosulfophthalein with (80 ± 29) or without 5,5'-difluro-1,2-bis(O-amino phenoxy)ethane-N,N,N'N'-tetraacetic acid (101 ± 46). Two other treatments, N-acetylcysteine (183 ± 7) and dithiothreitol (166 ± 59) delayed the onset of toxicity. Finally, calpeptin (319 ± 34) which blocks activation of nonlysosomal proteases was ineffective.4 We concluded that early intervention on the pathway to toxicity was most effective. The strategies detailed here may prove beneficial in treating hepatotoxicity seen following nitrofurantoin therapy.