bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of chronic and acute ethanol treatment on morphology, lipid peroxidation, enzyme activities and Na+ transport systems on WRL-68 cells
Authors: Gutiérrez-Ruiz MC , Bucio L. , Souza V. , Cárabez A. 
Published: December 2008

In this study we measured some parameters that are asso ciated with ethanol damage to the liver. The method allowed us to determine the injury that chronic and acute ethanol treatments produce at the cellular level without interference from homeostatic or compensatory mecha nisms. The system used is a hepatic fetal human cell line, WRL-68, which retains, in culture, many of the liver-spe cific functions. WRL-68 cells do not metabolise ethanol, and consequently we could evaluate the effect of ethanol alone. We explored two different conditions: 30 days with 0.1 M ethanol (chronic treatment) and 24 h in the presence of 0.5 M ethanol (acute treatment). 1 The transmission electron microscopy studies revealed, in both treatments, the presence of granules not usually present in the cytoplasm of control cells and morphologi cal mitochondrial alterations in chronically treated cells. 2 Lipid peroxidation, measured as the rate of malondi aldehyde production, increased three and a half times in acutely treated cells and about twofold in chronically treated cells. 3 The percentage of total activity (activity in the medi um/(activity in the medium + activity of the cells). 100) and the enzymatic activity in the culture medium of gamma glutamyl transpeptidase (GGT), alanine amino transferase (ALAT), aspartate amino transferase (ASAT) and alkaline phosphatase (AI-P), increased. 4 We measured some parameters related to the transport of sodium across the membrane. Cells chronically treated with ethanol had higher rate constants and effluxes than control cells. There was no difference between the total and passive efflux. Ethanol treated cells apparently lacked the ouabain sensitive pathway. In acutely treated cells, the total sodium efflux and the rate constant were enhanced. Sodium pools in the acutely treated cells were diminished and active sodium pumping was seven times higher than in control cells. 5 We determined the number of high affinity ouabain binding sites per cell. Ethanol did not alter the number of pumps, rather it seems to induce a functional alteration. Our results indicate that ethanol per se induces lipid per oxidation, alters enzymatic activities, sodium transport systems, sodium pools and cellular morphology, and that all these changes may be partly responsible for ethanol- induced hepatotoxicity. The data compare favourably with those reported in the literature for many different systems. Therefore our model for studying the mechanism of alco hol effects appears to be valid, with the advantage of being able to compare experiments that can be done in the same system and under the same conditions.
Investigation of immunotoxicity of supercypermethrin forte in the Wistar rat
Authors: Tulinská J. , Kubová J. , Janota S. , Nyulassy Š. 
Published: December 2008

The study was done to find out whether subacute exposure to supercypermethrin forte (SCM) affected cellular and humoral immunity. Groups of 10 male Wistar rats were given SCM by gav age for 28 days at 12.5 mg kg-1 day-1 (1/14 LD50), 8.75 mg kg-1 day-1 (1/20 LD50) and 4.38 mg kg-1 day-1 (1/40 LD50) and the response of splenocytes to mitogens, natural killer cell activity, plaque forming cell assay and phagocytosis were examined. The response of splenocytes to the mitogens phyto haemagglutin and concanavalin A, and to a T-dependent antigen (sheep red blood cells), was enhanced at 1/40 LD50 SCM, and at 1/20 and 1/14 LD50 these variables were sup pressed. In the group exposed to 1/14 LD40 SCM the sup pression was statistically significant. A non significant but dose-related increase in NK-cell activity was observed. The phagocytic activity of polymorphes was not signifi cantly affected. Thus, SCM at 1/14 LD50 had significant adverse effects on a number of immunological functions in rats, but lower doses had no effect on these activities.
Poisoning due to Chinese proprietary medicines
Authors: Chan Thomas YK , Lee Kenneth KC , Chan Albert YW , Critchley Julian AJH 
Published: December 2008

1 To determine the toxic potentials of those Chinese pro prietary medicines (CPM) which are commonly used for self-poisoning by adults in Hong Kong, all patients admit ted to four of the eight general medical wards at the Prince of Wales Hospital between January 1988 and December 1993 were retrospectively studied. 2 There were 54 women and 17 men with their age rang ing from 15 to 86 years. Twenty-three subjects (32%) also took alcohol, chemicals or drugs. Of the 51 subjects (72%) who had taken topical medicaments, 22 had no symptoms while 28 had minor features of gastrointestinal irritation ( n = 26), mild ( n = 2) or severe ( n = 1) salicylate poisoning. Of the 17 subjects (24%) who had taken CPM tablets/cap sules, nine had mild symptoms including nausea/vomiting and drowsiness. The three remaining patients (4%) who had ingested liquid CPM preparations were asymptomatic. Elevated plasma salicylate or paracetamol concentrations (> 0.1 mmol l-1l) were found in some patients who had taken topical medicaments and CPM tablets/capsules, respectively. All the 71 patients completely recovered. 3 Most of the CPM used for self-poisoning in Hong Kong were of low to moderate toxicity except for those contain ing wintergreen oil (methyl salicylate).
Potential neurotoxicity of a novel aminoacridine analogue
Authors: Walker TM , Starr B. , Dewhurst BB , Atterwill C. 
Published: December 2008

1 A class of compounds, 9-aminoacridines, have long been known to be reversible inhibitors of acetyl cholinesterase (AChE - EC 3.1.1.7), the most familiar of which is 9-amino-1,2,3,4-tetrahydroacridine (Tacrine). 2 A novel aminoacridine was synthesised: - 2-tertiary butyl-9-amino-1,2,3,4-tetrahydroacridine (2tBuTHA). 3 In vitro comparisons of the acetylcholinesterase inhibitory potential and neurotoxicity compared to Tacrine were performed using a chemically differentiated neuroblastoma cell line (Neuro 2A). 2tBuTHA, but not Tacrine, was cytotoxic to the neural cell following 20 h exposure, despite being the least potent AChE inhibitor (IC80 AChE 12.53 μM +/- 1.14 s.e.m., Neutral Red Uptake IC50 9.53 μM +/- 0.98 s.e.m., MTT Reduction IC80 14.6 μM +/- 1.43 s.e.m.). 4 In vivo studies used a novel application of a five arm radial maze to assess neuropharmacological effects on working memory in control and Scopolamine (1 mg kg-1 i.p.) treated mice. There was an impairment of short term cognitive function with 2tBuTHA (15 mg kg -1 i.p.), but not Tacrine (10 mg kg-1 i.p.) which improved the Scopolamine deficit as expected. 5 This combined in vitro and in vivo data infers a neuro toxic property for the novel compound 2tBuTHA, a close structural analogue of Tacrine.
Effect of dermal application of hexachlorocyclohexane (HCH) on male reproductive system of rat
Authors: Prasad AK , Pant N. , Srivastava SC , Kumar R. , Srivastava SP 
Published: December 2008

1 The toxic manifestations of dermally applied hexa chlorocyclohexane (50 mg or 100 mg kg-1 body weight day -1, 5 days in a week for 120 days) on testes and sperm of rat have been investigated. 2 The results indicate that exposure of HCH through the dermal route could lead to an alteration in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH), γ-glutamyl transpeptidase (γ-GT) and β-glucuronidase (βGluc.) associ ated with specific cell types. 3 Significant quantities of HCH and its isomers accumu lated in testes as well as sperm of treated rats. 4 HCH exposure also led to a decrease in serum testos terone levels, epididymal sperm count, sperm motility and an increase in the percentage of abnormal sperm. 5 These observations indicate the possibility of adverse effects of HCH on the male reproductive functions of men exposed dermally to this pesticide in industry or during spraying in the field.
Concentration-response relationships for three nonsteroidal anti-inflammatory drugs in the rat intestine
Authors: Ford J. , Houston JB 
Published: December 2008

1. The effect of diclofenac, piroxicam and (S+)-ibuprofen upon the rat intestine has been measured at constant drug plasma concentrations in the rat, using (51Cr)-EDTA intestinal permeation as a measure of damage. Initially disposition studies after sc administration of the three NSAIDs were carried out. From these studies it was found that constant-rate iv infusions were necessary to maintain plasma concentrations of diclofenac and (S+)-ibuprofen. Administration of piroxicam by sc bolus gave relatively constant plasma concentrations, thus iv infusions were not necessary to obtain concentration-response data for this drug. Relative potency was found by comparing the con centration-response profiles of the three NSAIDs and the rank order of potency obtained was: diclofenac > piroxi cam > (S+)-ibuprofen. 2. The effect of mode of administration upon intestinal damage was also investigated using diclofenac. Intestinal permeability was measured in rats given diclofenac either by sc bolus or iv infusion and dose-response data com pared. It was found that for the same dose, administration by sc bolus gave a higher degree of damage than by iv infusion.
Effect of pyridostigmine pretreatment on cardiorespiratory function in tabun poisoning
Authors: Worek F. , Kleine A. , Szinicz L. 
Published: December 2008

1 The effect of pyridostigmine on cardiorespiratory func tion after oxime+atropine injection was investigated in tabun poisoned guinea-pigs and without tabun poisoning.2 The trachea, a carotid artery and jugular vein were can nulated in female urethane-anaesthetised Pirbright white guinea-pigs. After baseline measurements the ani mals received pyridostigmine (0.05 μmol kg-1) and 30 min later atropine (29.5 μmol kg-1) plus obidoxime, HI 6 or HL6 7 (30 or 100 μmol kg-1) or tabun (1.85 μmol kg-1= 5 x LD50) followed by oxime+atropine treatment (all i.v.). Erythrocyte, brain and diaphragm acetyl cholinesterase (AChE) activity were determined. Similar groups without pretreatment were included for compar ison.3 Pyridostigmine aggravated the oxime+atropine induced hypotension and prevented the increase in heart rate but not the respiratory stimulation. The pyridostigmine inhibited AChE recovered only in the 100 μmol kg-1kg oxime groups at the end of the experiment.4 In tabun poisoning, pyridostigmine reduced the oxime+atropine induced circulatory recovery and decreased the survival time and rate. It did not affect the therapeutic oxime+atropine effect on respiratory function.5 These results suggest that pyridostigmine enhances oxime+atropine related circulatory depression which may be the reason for the reduced efficacy of oxime+atropine treatment in tabun poisoning. The pos sible mechanisms are discussed.
Effect of oral administration of carbofuran on male reproductive system of rat
Authors: Pant N. , Prasad AK , Srivastava SC , Shankar R. , Srivastava SP 
Published: December 2008

1 Carbofuran was administered orally to adult male rats at dose levels of 0.1, 0.2, 0.4 or 0.8 mg kg -1 body weight, 5 d wk-1 for 60 days. A dose dependent decrease was observed in body weight of rats treated with 0.2-0.8 mg carbofuran kg -1 body weight 2 A significant decrease in the weight of epididymides, seminal vesicles, ventral prostate and coagulating glands was observed at various test doses of carbofuran except at the lowest dose. 3 Decreased sperm motility, reduced epididymal sperm count along with increased morphological abnormali ties in head, neck and tail regions of spermatozoa were observed in rats exposed to 0.2, 0.4, or 0.8 mg carbo furan kg-1 body weight. 4 In addition, significant alterations were observed in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH) (decreased), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT) (increased) depending on dose. 5 Histologically, the results indicated the toxicity of carbo furan on testes depending on dose. The changes pre dominantly consisted of moderate oedema, congestion, damage to Sertoli cells and germ cells, along with the accumulation of cellular debris and presence of giant cells in the lumen of a few seminiferous tubules which showed disturbed spermatogenesis with the higher doses of carbofuran. 6 These observations determined a no effect level dose of 0.1 mg kg-1 body weight of carbofuran on the biochemi cal and morphological indices studied for male repro ductive toxicity assessment in the rat model. The results of the present study provide first hand information on the reproductive toxicity of carbofuran in male rats.
Small-intestinal transfer mechanism of prunasin, the primary metabolite of the cyanogenic glycoside amygdalin
Authors: Strugala GJ , Stahl R. , Elsenhans B. , Rauws AG , Forth W. 
Published: December 2008

1 The small-intestinal transfer of prunasin (D-mandelo nitrile-β-D-glucoside), the primary metabolite of amyg dalin which is not absorbed in the small intestine as such, was studied in rat jejunum and ileum in vitro. 2 As shown by high pressure liquid chromatography, prunasin is transferred essentially intact across the intesti nal wall, without cleavage of the glycosidic bond and thus no formation of benzaldehyde or cyanide during the mucosal passage. 3 Only the jejunal transfer of prunasin followed satura tion kinetics (vmax = 1.6 μmol cm-1 min-1; KT = 460 μmol l-1) and exhibited a clearsodium-ion dependence. As indicated by the temperature dependence, only the jejunal mucosa- to-serosa transfer and the corresponding tissue uptake of prunasin required apparently high activation energies. Transfer in the terminal ileum showed diffusion character istics. 4 Jejunal methyl α-D-glucoside transfer was inhibited by the presence of prunasin. Furthermore, the tissue uptake of methyl α-D-glucoside in rat jejunum was competitively inhibited by prunasin. 5 The results indicate that prunasin is absorbed unmetabolised in the jejunum of the rat via the transport system of glucose.
Usage and adverse effects of Chinese herbal medicines
Authors: Chan Thomas Y K , Critchley Julian A J H 
Published: December 2008

The great majority of Chinese herbal preparations are safe, and in the past, some useful Western drugs have been derived from these herbs. Nearly all serious poisonings are due to the few preparations containing aconitine, podophyllin or anti cholinergics or else proprietary preparations containing dangerous Western drugs or heavy metals. Both medical professionals and the general public should be alerted to the potential toxicity of herbal remedies. There should be frequent monitoring of Chinese herbal medicines or their derivatives, such as some Chinese proprietary medicines, for undeclared Western drugs and heavy metals. Mothers should be discouraged from treating their children with herbal or proprietary medicines. There should be con tinuing efforts to collect safety information on these widely used products.
Complexation of intracellular cyanide by hydroxocobalamin using a human cellular model
Authors: Astier Alain , Baud Frederic J 
Published: December 2008

1 The rational for administering hydroxocobalamin (OHCbl) as an antidote to cyanide poisoning is based on the high affinity ofCN ion for cobalt compounds. However, only few data are available on the influence of OHCbl on the intracellular cyanide pool.2 In human fibroblasts incubated for 10 min with 500 μM of [14C] cyanide, the accumulation ratio was 25 at 37°C (10.45 ± 1.51 mM) and 11.9 at 4°C.3 Using the monoblastic U-937 cell line, a rapid uptake of radioactive cyanide was observed with a maximum accumulation ratio of 1.97 at 5 min.4 A linear relationship between cyanide uptake by U-937 cells and cyanide concentration in incubation medium (10-500 μM; 5 min) was found suggesting a first order process (k= 0.25 min-1).5 After incubation of fibroblasts with 500 μM of OHCbl, a 75% decrease of intracellular cyanide was observed, with concomittant formation of intracellular cyanocobalamin CNCbl (intracellular/extracellular ratio: 158).6 These findings suggest that OHCbl is able to penetrate into heavily cyanide loaded cells and to complex cyanide to the non-toxic CNCbl form.
Immunohistochemical properties of dipyrone-induced cytochromes P450 in rats
Authors: Kraul H. , Pasanen M. , Sigusch H. , Stenbäck F. , Park S-S. , Gelboin HV , Pelkonen O. 
Published: December 2008

1 Rat hepatic cytochrome P450s induced by dipyrone were studied enzymatically, immunochemically and immunohistochemically.2 Dipyrone administered to male Wistar rats increased pentoxyresorufin O-depentylation (PROD), ethoxyresor ufin O-deethylation (EROD) and 7-ethoxycoumarin O- deethylation (ECOD) activities up to 44-, 1.9-, and 2.6-fold, respectively. Aryl hydrocarbon hydroxylase (AHH) activ ity was not affected.3 Immunoinhibition with the monoclonal antibody (Mab) 2-66-3 (to CYP2B1/2) markedly decreased PROD and EROD activities, but not AHH activity. The Mab 1-7-1 (to CYP1A1/2) was without effect.4 Histochemically, the Mab 2-66-3 gave a strong and uniform staining in livers from dipyrone-treated rats, whereas the Mab 1-7-1 gave a positive reaction in a narrow perivenous strip.5 The induction pattern as well as inhibition by the Mabs convincingly demonstrate the predominant production of CYP2B1/2 in the induction spectrum of dipyrone. The increase in enzyme activities other than PROD may be due to the overlapping substrate specificity of CYP2B1/2 enzymes. The immunohistochemical analysis also indi cated the participation of CYP1A1/2.
Effect of short-term dietary administration of eugenol in humans
Authors: Rompelberg Cjm , Vogels Jtwe , de Vogel N. , Bruijntjes-Rozier Gcdm , Stenhuis WH , Bogaards Jjp , Verhagen H. 
Published: December 2008

1 In order to study the antigenotoxic potential of eugenol in humans, ten healthy non-smoking males ingested a daily amount of 150 mg eugenol or the placebo for seven consecutive days. After a washout period of one week, groups ingesting eugenol or the placebo were crossed and received the other treatment for seven consecutive days. 2 On days 8 and 22 blood samples were taken for the assessment of standard clinical biochemical parameters. To study the possible antigenotoxic effect of eugenol, on day 8 and 22 blood samples were collected and exposed in vitro to the established genotoxic agents mitomycin C and vinblastine. After exposure the percentage of cells with chromosome aberrations and micronuclei was deter mined in cultured white blood cells. On days 8 and 22 paracetamol (500 mg p.o.) was administered as test substance to measure phase-II biotransformation capa city. Glutathione-S-transferase (GST) activities were determined in erythrocytes and blood plasma. 3 No significant differences in the clinical biochemical parameters were detected between the eugenol-period and the placebo-period, indicating that daily administration of 150 mg eugenol for 7 days has no toxic affects. 4 No significant differences on the cytogenetic para meters were found after ingestion of eugenol. Thus, there are no indications for an antigenotoxic potential of eugenol in humans, consuming daily 150 mg eugenol for 7 days. 5 A significant reduction in α-class GSTs in plasma (P<0.05), but not in the other measured biotransformation parameters, was found in volunteers during the eugenol- period as compared to the placebo-period. This may either reflect GST-inhibition by eugenol or protection against background damage of liver cells by eugenol.
Alternatives to the 2-species bioassay for the identification of potential human carcinogens
Authors: Ashby J. 
Published: December 2008

It is proposed that the standard 2-species rodent cancer bioassay protocol, as perfected by the US National Toxicology Program (NTP), has already fulfilled its most useful role by providing an unequalled carcinogenicity database by which to re-assess the type of carcinogen worthy of definition. Continued use of this resource and time consuming protocol can no longer be justified, except in rare circumstances of high and protracted human exposure to a chemical of unknown carcinogenicity. In those rare instances an enlarged bioassay of three or four test species should perhaps be considered, there being nothing fundamental about the rat/mouse combination. In the large majority of cases, however, a practical estimation of the carcinogenic potential of a chemical can be formed in the absence of lifetime carcinogenicity bioassay data. This can be achieved by its sequential study, starting with an appreciation of its chemical structure and anticipated reactivity and mammalian metabolism. After the short- term evaluation of a range of additional properties of the agent, including its genetic toxicity, rodent toxicity and tissue-specific toxicity, confident predictions of the genotoxic and/or non-genotoxic carcinogenic potential of the agent can be made. In most situations these predictions will be suitable for framing hazard reduction measures among exposed humans. In some situations it may be necessary to evaluate these predicted activities using limited bioassays, a range of which are considered. Extensions of these limited carcinogenicity bioassays to a standard 2-year/2-species bioassay can only be supported in cases where the non-carcinogenicity of the agent becomes the important thing to define.The US NTP have evaluated the carcinogenicity of ∼400 chemicals over the past 20 years, at a cost of hundreds of millions of US dollars. The experience gained by that and related initiatives, worldwide, can now be harnessed to classify thousands of priority chemicals as being either probable carcinogens or probable non- carcinogens. That can now be achieved using a fraction of the earlier resources and in a fraction of the time that would be required for the conduct of 2-species bioassays.The comfort factor for one group of people of the order of the present system, coupled to the comfort factor for another group of the delay in carcinogenicity assessment enforced by the present council of perfection, are the two main factors delaying transfer to a streamlined system for assessing the carcinogenic potential of chemicals to humans. A third delaying factor in the need for new and focused test data. Coordinated acquisition of such data could rapidly remove the first two obstacles.
Triphenyltin acetate toxicity : a biochemical and ultrastructural study on mouse thymocytes
Authors: Bollo E. , Ceppa L. , Cornaglia E. , Nebbia C. , Biolatti B. , Dacasto M. 
Published: December 2008

1 Triphenyltin acetate (TPTA) has been shown to exert in vivo a selective toxic effect on the immune system. To assess in vitro possible alterations induced by TPTA exposure, primary cultures of mouse thymocytes were incubated up to 24 h with graded amounts (1-12 μM) ofthe organotin. 2 The cytotoxic activity has been evaluated with the MTT colorimetric assay, the neutral red (NR) assay and the lactic dehydrogenase (LDH) cellular release. Cell pellets were fixed with 2.5% glutaraldehyde, resin-embedded and ultrathin sections were observed through transmission electron microscopy. 3 After 2 h of incubation, dose-dependent increases of cytotoxicity were observed in thymocytes submitted to MTT and NR tests (up to 41.43% and 18.9%, respectively), while 22 h later this overt effect on cell viability was noticed merely in cells exposed to 12 μM TPTA. Dose- dependent increases of LDH leakage in the culture medium were observed all throughout the study. 4 Morphological investigations revealed features (chro matin condensation, cell membranes fragmentation and formation of membrane bound apoptotic bodies) sugges tive of apoptosis. 5 This study indicates that TPTA is cytotoxic to mouse thymocytes: morphologically, the rising of apoptosis is likely to be recognized, as previously reported in different in vitro studies with other immunosuppressive agents as dioxin and corticosteroids.