bluuebunny/crossref_metadata_2025 huggingface dataset:
Trichothecene toxicity on human megakaryocyte progenitors (CFU-MK)
Authors: Froquet R , Sibiril Y , Parent-Massin D
Published: April 2003

Trichothecenes are mycotoxins produced by various species of fungi, which can occur on various agricultural products. Among these compounds, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and deoxynivalenol (DON) are the most naturally encountered and the most potent trichothecenes. Consumption of trichothecene contaminated foods by farm animals and humans leads to mycotoxicosis. Trichothecenes are known to induce haematological disorders such as neutropenia, aplastic anemia and thrombocytopenia in humans and animals. Four trichothecenes, T-2 toxin, HT-2 toxin, DAS and DON have been tested on human platelet progenitors (CFU-MK) using a culture model of CFU-MK optimized for toxicological studies. Trichothecenes cause, at low concentrations, cytotoxic effects in megakaryocyte progenitors, which could induce thrombocytopenia. Sensitivity of human CFU-MK is compared to respective sensitivities of human red blood cell progenitors (BFU-E) and white blood cell progenitors (CF-U-GM) that were described in previous works.
The efect of hexafluorocyclobutene on rat bronchoalveolar lavage fluid surfactant phospholipids and alveolar type II cells
Authors: Jugg B , Jenner J , Hughes J N , Rice P
Published: April 2003

Hexafluorocyclobutene (HFCB), a reactive organohalogen gas, causes overwhelming pulmonary oedema. We investigated its effect on the rat lung surfactant system, comparing its action on type II pneumocytes with airexposed rats. The inflammatory cell population and protein content of bronchoalveolar lavage fluid was analysed following exposure to air or HFCB (LCt30). Six rat lung phospholipids were measured by high-performance liquid chromatography, following solid phase extraction (SPE) from lavage fluid. Transmission electron microscopy (TEM) was used to visualise effects on alveolar type II cell ultrastructure. HFCB caused changes in cell populations and increased lavage fluid protein compared to controls, suggesting a permeability oedema. Changes in the total amount and percentage composition (sustained decrease in phosphatidylglycerol and phosphatidylcholine) of surfactant phospholipids also occurred. TEM observations indicated no direct ultrastructural damage to the type II cells, but showed initial, rapid release of surfactant into the alveolar space. HFCB altered the surfactant system in a manner similar to that shown following another reactive organohalogen gas, perfluoroisobutene (PFIB), but differently to that after phosgene. These differences suggest different mechanisms of action even though pulmonary oedema is the final injury for all gases. Better knowledge of the mechanisms involved will improve prospects for prophylactic/therapeutic intervention.
Changes in zinc and copper homeostasis in human livers and kidneys associated with exposure to environmental cadmium
Authors: Satarug S , Baker J R , Reilly P Eb , Moore M R , Williams D J
Published: April 2003

This study was undertaken to assess changes in zinc and copper homeostasis in human tissues that could be attributed to human exposure to environmental cadmium, using samples of lung, liver and kidney cortex of 61 Queensland residents, aged 2 to 89 years, who had died of accidental causes. None of the subjects were exposed to cadmium in the workplace. Levels of zinc in liver and kidney cortex samples showed inverse associations with donor age whereas zinc in lung only showed inverse association with gender. Lung zinc levels in females were 14% lower than in males. Zinc in liver and kidney cortex samples were found to exist in at least two pools; one was associated with cadmium that bound to metallothionein (MT) and the other was associated with non-MTbound copper. Inliver, the amounts ofzinc inthe MT pool were smaller compared to those in non-MT pool given that only 7% of zinc variations were explained by cadmium whereas 22% of the liver zinc variations were accounted for by non-MTbound copper. In sharp contrast, larger amounts of zinc in kidney cortex samples were in the MT pool, compared to those in the non-MT pool given that cadmium was found to explain 69% of total zinc variation whereas copper explained only 17% of kidney zinc variations. The levels of copper in liver were found to be increased by 45-50% in subjects with high cadmium exposure level, compared to subjects ofsimilar ages with medium exposure level. The levels of zinc and copper in kidney cortex samples in the subjects with high cadmium exposure were both found to be significantly elevated compared to those found in the medium-exposure group whereas copper contents were about 19-23% greater than in medium-as well as low-exposure groups. Taken together these results indicate increased sequestration of zinc and copper in liver and kidney cortex samples. The increases in metal sequestra-tions were observed in liver samples having cadmium contents of greater than 1 μg/g wet weight and in kidney cortex having cadmium contents of greater than 26 μg/g wet weight. Zinc and copper contents in lung of this sample group, however, were not associated with cadmium due probably to lower exposure levels compared to those of liver and kidney.
Carbamazepine poisoning: treatment with plasma exchange
Authors: Duzova A , Baskin E , Usta Y , Ozen S
Published: April 2003

Lethal cases due to carbamazepine overdose have been reported. There are contradicting reports about the efficiency of hemodialysis, hemoperfusion and plasmapheresis for the treatment of carbamazepine poisoning. We present a case of carbamazepine intoxication successfully managed with plasma exchange. The patient was a 15-year-old girl. On admission there was no evidence of trauma, Glascow Coma Scale scored 6. Further questioning of the parents revealed the patient had taken at least 23 tablets of Tegretol® (4.6 g) 6 h before the admission. The carbamazepine level was 190μmol/l. Orogastric lavagewasfollowedby activated charcoal. Within 20 h after admission there was no improvement in her neurological status. It was thus decided to perform plasmapheresis. At the end of the procedure she started to respond to verbal stimuli. Carbamazepine level immediately after the procedure was 101 μmol/l, and at the 36th, 60th and 84th hours were 72, 33 and 20 μmol/l, respectively. The patient was discharged on the fourth day. We have not observed any rebound in our patient. Thus we suggest that simple plasma exchange by plasma replacement is a cheaper and effective method for the treatment of intoxication with carbamazepine orsimilar drugs.
The effects of alcohol and diallyl sulphide on CYP2E1 activity in humans: a phenotyping study using chlorzoxazone
Authors: Loizou G D , Cocker J
Published: April 2003

The effects of acute administration of dietary levels of ethanol and the garlic oil extract, diallyl sulphide (DAS), on cytochrome P450 2E1 (CYP2E1) activity in volunteers were studied using the selective probe substrate, chlorzoxazone (CZX). The ratio of the CZX metabolite 6-hydroxychlorzoxazone (6-OHCZX) to CZX was taken to indicate CYP2E1 activity. The mean differences between the baseline and DAS-treated (0.2 mg/kg) CYP2E1 activities were significantly different (two-tailed p value=0.0242, n =8). Likewise, the mean differences between the baseline and ethanol-treated (0.8 g/kg) CYP2E1 activities were also significantly different (two-tailed p value=0.0005, n=7). The reduction in invivo CYP2E1 activity by DAS is consistent with reported inhibition observed in vitro. The marked reduction in CYP2E1 activity following acute ingestion of ethanol is consistent with a competitive inhibition mechanism of CZXmetabolism.The inhibitory effect of DAS maybe additive with daily consumption of Allium vegetables in particular. This may explain the lower 6-OHCZX/CZX metabolic ratios measured in various European and Mexican cohorts and is consistent with the lower incidence of stomach, liver and colon cancers observed in southern Europeans.
Effects of water-soluble antioxidant from spinach, NAO, on doxorubicin-induced heart injury
Authors: Breitbart E , Lomnitski L , Nyska A , Malik Z , Bergman M , Sofer Y , Haseman J K , Grossman S
Published: April 2003

Doxorubicin (DOX) produces clinically restorative responsesinnumeroushumancancers,butitscardiotoxicity has limited its usefulness. Because reactive oxygen species may affect DOX-induced antitumor activity and cardiotoxicity, weevaluated the prophylactic effect ofspinachnatural antioxidant (NAO) on DOX-induced cardiotoxicity and oxidative stress in female Balb/c mice using histological, electron microscopical and biochemical parameters. Mice were treated with NAO for 7 days prior to and/or for 6 days after DOX administration. Pretreatment with NAO (cumulative dose: 130 mg/kg) did not hinder the effectiveness of DOX. Light and electron microscopy of DOX-treated heart revealed myocardial degeneration. When administered combined before and after DOX, NAO conferred the most significantcardiacprotection.TheeffectsofNAOonthelipid peroxidation product, malondialdehyde, and on H2O2 / hydroperoxides were examined on day 6 following DOX administration; levels of both were elevated in DOX-treated mice, compared to control. Pretreatment with NAO prevented these changes. Pretreatment with NAO before DOX administration decreased catalase and increased super oxide dismutase activities compared to the DOX group. Our results suggest usage of NAO in combination with DOX as a prophylactic strategy to protect heart muscle from DOX inducedcellulardamage.
Chronicity of neurological features in ciguatera fish poisoning
Authors: Chan T YK , Kwok T CY
Published: April 2003

A 43-year-old woman complained of colicky abdominal pain, followed by numbness, myalgias, and muscle weakness in the four limbs after eating a grouper (Epinepheius spp.). She presented to our hospital 36 hours later with increased myalgias, muscle weakness, and malaise. On examination, the muscle power and sensation in her four limbs appeared to be normal. She was given an intravenous infusion of mannitol 20% (200 ml over 1 hour) and an intramuscularinjection ofdiclofenac (75mg).Hermyalgias then improved andshe was discharged. She presented to our hospital again 1 week later with poor appetite, malaise, numbnessofthefourlimbs,andincreasedmuscleweakness. On examination, the muscle weakness was more marked in the lower limbs (4+/5) than in the upper limbs (5 /5) and proximally than distally. She also had some difficulty in getting up from a squatting position. She was given another intravenous infusion of mannitol 20% (200 ml over 1 hour), following which there was subjectively slight improvement inhermuscleweakness.Herplasmacreatinephosphokinase level was normal. Electromyography performed 4 weeks later revealed no abnormalities. When she was reviewed 45 days after the consumption of the grouper, her muscle weakness and malaise had improved considerably. She could then stand up from a squatting position. However, mild impairment of finger grip was still present. Chronicity of neurological features in other reported cases (e.g., chronic fatigue, relapse of symptoms after exposure to ciguateric fish or alcohol, and peripheral neuropathy) may also indicate a lengthy persistence of ciguatoxins in the body.
Chlorzoxazone: a probe drug the metabolism of which can be used to monitor one-point blood sampling in the carbon tetrachloride intoxicated rat
Authors: Tanaka E
Published: April 2003

In this study, we have carried out an investigation to determine if chlorzoxazone (CZX) is a suitable probe drug for predicting hepatic injury in carbon tetrachloride (CCl4)-intoxicated rats. The animals received oral doses of CCl4 (0.25, 0.5 and 1 ml/kg) 24 h prior to intraperitoneal administration of CZX. The total CYP and CYP2E1 content, as well as the aniline and CZX hydroxylase activity (V max and CLint), was reduced depending on the dose of CCl4 administered. At the highest concentration (128 mM) of diethyldithiocarba mate, a specific inhibitor of CYP2E1, the production of 6-hydroxychlorzoxazone (HCZX) in microsomes from CCl4 treated rats was reduced by about 85%. The IC50value in microsomes from CCl4 treated rats was between 3 and 5 M. The production of HCZX and the activity of aniline hydroxylase in CCl4 treated rats correlated with the amount of rat CYP2E1 protein (r =0.881, P <0.001 and r =0.822, P <0.001, respectively). The elimination of CZX by CCl4 treated rats was reduced and the HCXZ production in the CCl4 treated group was less than that in the olive oil-treated control group. The correlations between the intrinsic clearance (CLint:V max /Km) in vitro and the total body clearance (CLtot) of CZX hydroxylation and the elimination half-life (t1/2) of CZX in vivo in CCl4 treated rats were high (r =0.839, P <0.001 and r = 0.828, P <0.001, respectively). In addition, the metabolic plasma HCZX/CZX ratio did not require multiple blood sampling and, 2 h after CZX administration in vivo, there was also a high correlation with the CLint (V max / K m) in vitro (r = 0.909, P<0.01). In conclusion, these results from this study demonstrate that CZX is a good probe for monitoring the inhibition of metabolism in rats due to CCl4 treatment.
Decreased plasma and cerebrospinal fluid glutamine concentrations in a patient with bialaphos poisoning
Authors: Ohtake T , Yasuda H , Takahashi H , Goto T , Suzuki K , Yonemura K , Hishida A
Published: April 2003

A 47-year-old Japanese woman undergoing maintenance hemodialysis (HD) was admitted to our hospital because of poisoning with the herbicide bialaphos. Respiratory arrest and loss of consciousness ensued rapidly, accompanied by convulsions and nystagmus. Treatment with HD and direct hemoperfusion, followed by HD alone, effectively removed bialaphos and its chief toxic metabolite (L-AMPB) from the circulation (bialaphos decreased from 0.33 to <0.05 g/ml andL-AMPBfrom14to0.86 g/ml). The glutamate concentration improved gradually after the removal of bialaphos and L-AMPB from plasma (plasma glutamate concentration: 250.4 nmol/l on day 5 to 120.6 nmol/l on day 26). Decreased glutamine concentration in cerebrospinal fluidwasdemonstratedforthefirsttimeaswellasinplasma, indicating glutaminesynthetase inhibition notonlyinplants but also in humans by bialaphos poisoning.
Stimulation of C32 and G361 melanoma cells using oleoyl acetyl glycerol and its effect on sulphur mustard cytotoxicity
Authors: Smith C N , Lindsay C D
Published: April 2003

Epidermal melanocytes have a higher sensitivity to sulphur mustard (HD) compared with other skin cell types.1 This may be due to the enzymatic production of melanin precursors exerting an additional cytotoxic effect following HD depletion of the cellular protectant, GSH.2,3 Stimulation of the protein kinase C pathway in melanocytes is known to increase melanin production in melanocytes and melanoma cell lines.4,5 In order to investigate the role of pigment synthesis in HD toxicology, cultures of an unpigmented melanoma cell line (C32) and of a pigmented melanoma line (G361) were treated with the potent diacyl glycerol analogue, oleoyl acetyl glycerol (OAG), in order to determine if protein kinase C-mediated increases in pigment production could increase sensitivity to subsequent HD exposure. Stimulation of C32 cells with OAG exerted a significant protective effect against the cytotoxic effects of HD. However, this was not due to increased melanin synthesis because this cell line cannot synthesize melanin pigments. The protective action observed is postulated to be due to modulation of protein kinase C activity. In contrast, stimulation of G361 melanoma cells with OAG resulted in an increased level of cytotoxicity upon subsequent exposure to HD. Protein kinase C controls several cellular pathways including checkpoints in the cell cycle, stalling the cell in G1 and promoting transition through the G2 /M boundary. Given the genotoxic properties of HD, these two points in the cell cycle are important in determining the overall cytotoxic effect of HD. Control of the cell cycle by protein kinase C modulation and manipulation of melanin synthetic pathways may have therapeutic benefits.
An in vitro comparison of the cytotoxicity of sulphur mustard in melanoma and keratinocyte cell lines
Authors: Smith C N , Lindsay C D , Hambrook J L
Published: April 2003

In vivo, the pigment producing melanocytes are the most susceptible cell type to sulphur mustard (HD) in the epidermal region of pig skin. It has been postulated that this is due to the melanogenic pathway producing a cytotoxic, free radical cascade within the melanocyte following HD poisoning, leading to cellular necrosis and subsequent inflammation. To test this hypothesis, the cytotoxicity of HD was tested in three human melanoma cell lines and compared to SVK-14 human keratinocytes, a cell line in which the response to HD has already been characterised. The results of both neutral red (NR) and gentian violet (GV) assays showed that all three melanoma cell lines, particularly the G361 line, were less susceptible to the toxic effects of HD than the SVK-14 keratinocyte cell line. Preliminary data indicate that the expression level of the DNA repair cofactor, proliferating cell nuclear antigen (PCNA), is up to 13-fold greater in the HD-resistant cell line G361 compared to the HD-sensitive SVK-14 cell line. The data point to the importance of DNA lesions in HD-induced cell death and to potential mechanisms associated with increased resistance to HD. A dose–response study was carried out to confirm the differences between these two cell lines. It was found that the G361 line is 5-fold more resistant to HD and 5.5-fold more resistant to the cytotoxic effects of H2O2 than the SVK-14 line, as determined by the MTT assay. The results suggest that differences in the relative efficiency of DNA repair processes may underlie these responses. Whilst the study indicates the limitations of using melanoma cell lines (in vitro) to model melanocyte responses to HD, analysis of the biochemical basis of the observed differences in sensitivity to HD could assist in the identification of novel therapeutic strategies against HD.
Three case reports of the use of haemodiafiltration in the treatment of salicylate overdose
Authors: Wrathall G , Sinclair R , Moore A , Pogson D
Published: April 2003

Aspirin (acetylsalicylic acid) is widely available without prescription. Although self-poisoning is rare, if severe it may be life threatening. Haemodialysis has been recommended in severe cases when salicylate levels exceed 7.3 mmol l-1. We describe three cases of severe salicylate poisoning, which were treated with continuous veno-venous haemodiafiltration (CVVHDF). All patients survived. The first case had already undergone haemodialysis before transfer to the ICU, where CVVHDF was commenced because salicylism persisted at 3 mmol l-1. A small reduction in serum salicylate was noted. In the second case, serum salicylate decreased from 8.5 to 3.5 mmol l-1 after 3 h of CVVHDF even though only minimal urine was produced. Our third case is a chronic overdose in whom serum salicylate decreased from 6.2 to 4 mmol l-1 after 4 h and to 1.4 mmol l-1 after a further 7 h. No bicarbonate was administered to this patient and elimination can only be attributed to CVVHDF and urinary clearance, which is known to be slow. We discuss the pathogenesis of severe salicylate toxicity and postulate that CVVHDF, which is widely used in the intensive care setting, may be a useful therapy in severely poisoned patients who are unstable and cannot undergo haemodialysis or in situations where haemodialysis is unavailable.
Applying hormesis in aging research and therapy
Authors: Rattan Sis
Published: April 2003

Biology of aging is well understood at a descriptive level. Based on these data, biogerontological research is now able to develop various possibilities for intervention. A promising approach for the identification of gerontogenes and gerontogenic processes is through the hormetic effects of mild stress on slowing down aging. Although there are several issues remaining to be resolved, specially with regard to the notion of mild stress, application of hormesis in aging research and therapy is a powerful new approach.
The implications of hormesis to ecotoxicology and ecological risk assessment
Authors: Chapman P M
Published: April 2003

Changes required for the explicit recognition of hormesis are outlined for both ecotoxicology and ecological risk assessment (ERA). A major research need is the extension of hormesis beyond chemical stressors to abiotic (e.g., habitat) and biotic stressors (e.g., species introductions, organism interactions). An overreaching research need is to determine for all stressors with model organisms, populations, and communities whether hormesis has positive, neutral, or adverse effects. The latter are the least likely; however, neutral effects cannot be ruled out. Based on our present state of knowledge, hormesis is likely to have more of an impact on ecotoxicology than on ERA. In the case of the latter, it is most likely to make a difference only in a detailed-level ecological risk assessment (DLERA), the most complex form of ERA. Further, for hormesis to be accepted fully into ecotoxicology or ERA will require a paradigm shift. Three ongoing paradigm shifts to which hormesis could be linked are: recognition of the low utility of no-observed-effects concentrations (NOECs); recognition of the need for special treatment of essential element dose–concentration responses, which are similar to hormesis; and the replacement of environmental toxicology with ecological toxicology (ecotoxicology).
Defining a tolerable concentration of methanol in alcoholic drinks
Authors: Paine A J , Dayan A D
Published: April 2003

Methanol, a potent toxicant in humans, occurs naturally at a low level in most alcoholic beverages without causing harm. However, illicit drinks made from “industrial methylated spirits” [5% (v/v) methanol:95% (v/v) ethanol] can cause severe and even fatal illness. Since documentation of a no-adverse-effect level for methanol is nonexistent in the literature a key question, from the public health perspective, is what is the maximum concentration of methanol in an alcoholic drink that an adult human could consume without risking toxicity due to its methanol content? Published information about methanol-intoxicated patients is reviewed and combined with findings in studies in volunteers given small doses of methanol, as well as occupational exposure limits (OELs), to indicate a tolerable (“safe”) daily dose of methanol in an adult as 2 g and a toxic dose as 8 g. The simultaneous ingestion of ethanol has no appreciable effect on the proposed “safe” and “toxic” doses when considering exposure over several hours. Thus, assuming that an adult consumes 425-ml standard measures of a drink containing 40% alcohol by volume over a period of 2 h, the maximum tolerable concentration (MTC) of methanol in such a drink would be 2% (v/v) by volume. However, this value only allows a safety factor of 4 to cover variation in the volume consumed and for the effects of malnutrition (i.e., folate deficiency), ill health and other personal factors (i.e., ethnicity). In contrast, the current EU general limit for naturally occurring methanol of 10 g methanol/l ethanol [which equates to 0.4% (v/v) methanol at 40% alcohol] provides a greater margin of safety.
Combined effects of acetaminophen, isopropylantipyrine and caffeine on pregnant and nonpregnant liver
Authors: Burdan F , Siezieniewska Z , Urbanowicz Z
Published: April 2003

The common effects of acetaminophen (APA), isopropylantipyrine (IPA) and caffeine on liver were examined in rats. The preparations were given in Tween-80 solution once daily, in a constant proportion of 5:3:1, during days 8 to14 of gestation (S1, S2, S3 groups) or between days 8 and 14 of the experiment in nonpregnant female Wistar rats (S1-NP, S2-NP, S3-NP groups). The administration was in three different doses: doses S1, S1-NP — 3.5 mg/kg APA, 2.14 mg/ kg IPA, 0.7 mg/kg caffeine; doses S2, S2-NP were 10 times higher; and doses S3, S3-NP 100 times higher than doses S1, S1-NP. There were two control groups (T, T-NP) with Tween-80. At day 21 of gestation/experiment blood was taken for determination of activity of alanine (ALA) and aspartate (AST) aminotransferase, lactate (LDH) and glutamate (GLDH) dehydrogenase, levels of bilirubin (BIL), urea (URE), total protein (TP) and thymol turbidity test (TTT). The liver sections were examined by light microscopy with four stains: hematoxylin and eosin (H+E), silver Gomori, van Gieson and periodic acid-Schiff (PAS). There was a statistically significant (P<0.05) increase in the GLDH (S3-NP, S2, S3 groups) and AST, LDH (S3 group) activity, a decrease in URE (S2, S3 groups) and decrease in TP (S3-NP, S2, S3 groups) compared to the corresponding control group. Significant differences were noted in activity of AST, GLDH, and levels of the URE and TP between pregnant and nonpregnant females. The treatment resulted in minimal reactive and degenerative changes in light microscopic pattern of liver.
Trichloroethylene induced testicular toxicity in rats exposed by inhalation
Authors: Kumar P , Prasad A K , Mani U , Maji B K , Dutta K K
Published: April 2003

Trichloroethylene (TCE) is an organic solvent used in dry cleaning, metal degreasing, thinner for paints and varnishes, anesthetic agent, and so forth. Human beings are appreciably exposed to TCE vapours by inhalation route. The present study has been undertaken to investigate whether TCE inhalation may also bring about testicular toxic effects. Our results indicate that inhalation of TCE by male rats for 12 and 24 weeks brings about significant reduction in absolute testicular weight, and alters marker testicular enzymes activity associated with spermatogenesis and germ cell maturation, along with marked histopathological changes showing depletion of germs cells and spermatogenic arrest.
Platelet dopamine receptors and oxidative stress parameters as markers of manganese toxicity
Authors: Husain M , Khanna V K , Roy A , Tandon R , Pradeep S , Seth P K
Published: April 2003

The present study has been undertaken to investigate whether neurotoxic effects of manganese (Mn) are reflected in platelets in rats to monitor the usefulness of platelet as peripheral model. Exposure of rats to Mn (10 or 15 mg/kg bw, i.p.) for 45 days caused a significant increase in membrane fluidity as evidenced by decrease in fluorescence polarisation in platelets (11% and 14%) and striatum (9% and 13%). These rats exhibited a significant increase in superoxide dismutase activity both in platelets (24% and 37%) and striatum (31% and 42%), respectively, in comparison to controls. Exposure of rats to Mn for 45 days (15 mg/kg bw, i.p.) caused a significant decrease in reduced glutathione content (platelets 20%, striatum 24%) and catalase activity (platelets 35%, striatum 44%) compared to control rats. Rats exposed to Mn (10 or 15 mg/ kg bw, i.p.) for 15 days exhibited a significant increase in dopamine receptors both in platelets (55% and 40%) and striatum (38% and 31%). The results suggest that exposure to Mn may alter the membrane functions and impair the anti-oxidant defense mechanism both in platelets and brain. The study also suggests that dopaminergic mechanisms are impaired following Mn exposure and such changes are reflected in platelets. Interestingly, parallel changes both in striatum and platelets, as observed in the present study, strengthen the usefulness of platelets as a peripheral neuronal model.
Protective effects of Emblica officinalis Gaertn. in cyclophosphamide-treated mice
Authors: Haque R , Bin-Hafeez B , Ahmad I , Parvez S , Pandey S , Raisuddin S
Published: April 2003

Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs in spite of its toxic side effects including immunotoxicity, hematotoxicity, mutagenicity and a host of others. The present study was undertaken to assess the protective effects of total aqueous extract of a medicinal plant, Indian gooseberry (Emblica officinalis Gaertn.) in mice treated with CP. These protective effects were studied on immunological parameters and kidney and liver antioxidants. Plant extract treatment at a dose of 100 mg/kg body weight per os (p.o.) for 10 days resulted in the modulation of these parameters in normal as well as CP (50 mg/kg)-treated animals. Plant extract in particular was very effective in reducing CP-induced suppression of humoral immunity. Plant extract treatment in normal animals modulated certain antioxidants of kidney and liver. In CP-exposed animals, plant pretreatment provided protection to antioxidants of kidney. Not only were the reduced glutathione levels significantly (p<0.001) increased but plant extract treatment resulted in restoration of antioxidant enzymes in CP-treated animals. It is suggested that E. officinalis or its medicinal preparations may prove to be useful as a component of combination therapy in cancer patients under CP treatment regimen. Human & Experimental Toxicology (2001) 20, 643–650.
Detection of poisoning by Impila (Callilepis laureola) in a mother and child
Authors: Steenkamp V , Stewart M J , Zuckerman M
Published: April 2003

Poisoning with impila (Callilepis laureola) is a recurring phenomenon in South Africa. Cases of poisoning with other plants which contain atractyloside also occur in Europe and the Americas. Since poisoning leads to rapid death from renal and/or hepatic failure, it is suspected that many cases are undiagnosed; this is especially so in South Africa, where patients may die without reaching hospital and do not often admit to ingestion of a traditional remedy.

We have developed a thin layer chromatographic method for the detection of impila constituents in urine. We describe the clinical symptoms and the application of the screening method to diagnosis in the case of a mother and child, who both showed symptoms of impila poisoning; the mother died but the child survived. This method is rapid and may be used for the definitive diagnosis in cases of poisoning with atractyloside-containing plants.
Identification of acrolein from the ozone oxidation of unsaturated fatty acids
Authors: Medina-Navarro R , Mercado-Pichardo E , Herńndez-Pérez O , Hicks J J
Published: April 2003

By-products of lipoperoxidation reactions may be associated with the genesis or the progression of several diseases as arteriosclerosis, diabetes and cancer, among many others. Acrolein, at first a widely distributed environmental pollutant, is currently known as a compound capable of being generated as a result of metabolic reactions within biological systems, highly toxic and the most electrophilic of the a, b-unsaturated aldehydes formed during lipoperoxidation. In the present study:

1 The separation of acrolein and malondialdehyde was achieved at alkaline pH with the use of high voltage capillary electrophoresis in uncoated fused-silica capillaries. 2 It was demonstrated how the oxidation of fatty acids (arachidonic/linoleic) with ozone generates, in dose-dependent form, acrolein as one of the by-products of the lipoperoxidation process. The oxidation of open human erythrocyte membranes with ozone also generated acrolein. 3 After aldolic condensation, aldol-acrolein derivative has a positive reaction with 2-thiobarbituric acid (TBA) and shows a maximum absorption at 498 nm. This novel characteristic is used in its identification after the separation of the by-products. 4 It is possible to suggest that in the classic reaction of the denominated thiobarbituric acid reactive substances (TBARS), when used as an indicator of the degree of peroxidation in biological systems, a portion of acrolein could be present but dwarfed by the TBAMDA adduct.
Species differences in arsenic-mediated renal copper accumulation: a comparison between rats, mice and guinea pigs
Authors: Hunder G , Schaper J , Ademuyiwa O , Elsenhans B
Published: April 2003

1 Administration of arsenite leads to an accumulation of copper in the rat kidney. Owing to the high retention of arsenic in the erythrocytes, however, the rat is considered to possess special toxicokinetics of arsenic and is therefore considered less comparable with other species in this respect. 2 Therefore, we compared the effect of dietary arsenite in mice and guinea pigs with that in rats. Each species was divided into four groups of animals according to the diets fed which contained increasing concentrations of sodium arsenite (NaAsO2;0,10,30and60mg As/kg of diet). Animals were killed after 1, 2 and 3 weeks. Tissues were sampled and analyzed for arsenic and other trace metals (Cu, Fe, Zn and Mn). 3 Compared to controls with copper levels of about 10 mg Cu/g wet wt. in the renal cortex, dietary administration of arsenite up to 60 mg As/kg of diet for 3 weeks to rats increased cortical levels to 65 mgCu/gwetwt.An increase of renal copper levels similar to that in rats, was only observed in guinea pigs but not in mice. Renal copper accumulation in guinea pigs was timeand concentration-dependent as in rats. Feeding a diet with 60 mg As/kg for 3 weeks increased cortical copper levels from about 6-40 mgCu/gwetwt.Renal copper levels in mice as well as other trace metal levels in guinea pigs and mice were not essentially altered by dietary arsenite. 4 The study shows that the renal copper-arsenic interaction is not restricted to the rat. Since in rats and guinea pigs, but not in mice, arsenic accumulated in the kidney rather similarly, a common mechanism is suggestive. As it was previously shown in rats that only inorganic arsenic is involved in this interaction, a rapid conversion of the inorganic form into methylated metabolites as in mice may diminish the extent of the renal copper accumulation whereas the lack of, or a less efficient, methylation as in guinea pigs or rats increases it.
Comparative acute toxicity of o-chlorobenzylidene malononitrile (CS) and oleoresin capsicum (OC) in awake rats
Authors: Debarre S , Karinthi L , Delamanche S , Fuché C , Desforges P , Calvet J-H
Published: April 2003

Tear gases are largely used to control civil unrest. Their incapaciting effects involve eyes, skin and respiratory tract. This study was performed to compare acute respiratory effects of o-chlorobenzylidene malononitrile (CS), oleoresin capsicum (OC) and their respective solvents in awake rats, using an integrated system of nose-only exposure and multiple monitoring of breathing. Aerosols were generated by a Collison Nebulizer from the solutions held in tear gas sprays. The reduction of minute ventilation, observed during a 5 min exposure, was significantly more important with CS than with OC: minute ventilation represented 29 + 8 and 50 + 6% of preexposure minute ventilation respectively (P <0.05). The reduction of minute ventilation observed with CS and OC solVents alone was not significantly different from that observed with the tear gases themselves. The decrease in minute ventilation observed, between the second and the fifth minute of exposure, was of the same level for repeated exposure separated by 24 h. Time necessary to recover to 80% of pre-exposure minute ventilation was not significantly different between the two tear gases: 722 + 272 and 691 + 262 s for CS and OC respectively (NS). Histological analysis of the trachea, performed at the end of exposures, revealed an increase in mucus secretion after exposure to OC and cytoplasmic vacuoles in epithelial cells after exposure to CS. In the lungs, interstitial oedema was observed after exposure to OC and emphysema after exposure to CS.
Tiopronin protects against the nephrotoxicity of cisplatin in the rat
Authors: Zhang J-G , Viale M , Esposito M , Lindup W E
Published: April 2003

1 Tiopronim (N-(2-mercaptopropionyl)-glycine) is a drug with a free thiol (sulphydryl) group that is used clinically. We have reported previously that tiopronin protects rat kidney slices in vitro from the nephrotoxic effects of cisplatin and does not reduce the antitumour activity of cisplatin. Tiopronin has been investigated therefore for its protective effects in rats in vivo. 2 The extent of kidney damage was studied 5 days after the administration of cisplatin. A single injection (i.p.) of cisplatin (6 mg/kg; 20,umollkg) to female Wistar albino rats caused a sustained decrease in body weight and, after 5 days, plasma urea, creatinine and kidney weight were increased. Tiopronin (2.5 mmol/kg, p.o.) ameliorated cisplatin nephrotoxicity when given 1 h before cisplatin. Tiopronin provided marked protection against cisplatin-induced increases in urea (from 237+19 mg to 48+23 mg/100 ml; control: 17+1) and creatinine (from 6.5+0.5 to 1.7+0.5 mg/100 ml control: 1.0 + 0.1). Tiopronin did not, prevent the body weight loss caused by cisplatin. In addition, an intraperitoneal dose (1 mmol/lkg) oftiopronin afforded similar protection to that of an oral dose. Rats that received an i.p. mixture of cisplatin (6 mg/kg) and tiopronin (65 mg/kg) displayed generally less toxicity, as indicated by a small fall in body weight and smaller increases in urea and creatinine and kidney weight. 3 The results show that tiopronin protects against cisplatin-induced nephrotoxicity. Oral administration of tiopronin may be a clinically useful way to prevent cisplatin nephrotoxicity.
From in utero and childhood exposure to parental smoking to childhood cancer: a possible link and the need for action
Authors: Sasco Annie J , Vainio Harri
Published: April 2003

The objective ofthe present work is to critically summarize published studies and reassess the state of knowledge on a highly controversial topic: the potential association between prenatal exposure to passive smoking as well as maternal active smoking and postnatal exposure to environmental tobacco smoke (ETS) and enhanced incidence of childhood cancer. Elements to be considered include the substantial proportion of pregnant women who remain smokers, the widespread nature of exposure to ETS during pregnancy as well as during childhood, the known toxicology of tobacco smoke, and in particular sidestream smoke, characterized by a rich carcinogen content, the specific metabolism of foetuses and new-borns and finally the amount of epidemiologic data already available. We conducted a thorough review of the literature to identify studies either exclusively dealing with the effects of passive smoking on the occurrence of childhood cancers or more generally etiologic studies of cancer, be it overall or site-specific. We identified close to 50 publications presenting pertinent results from epidemiological investigations and about 50 more on mechanisms and metabolism, smoking in pregnancy and exposure to ETS as well as selected reviews and commentaries. Collaborative epidemiological studies were conducted in the United Kingdom (UK), USA, Sweden, Netherlands and internationally (France, Italy). In addition, other studies were also available from the USA, UK, Canada, Australia, Sweden, Italy, Denmark and People' Republic of China. The vast majority were case-control studies dealing with all cancers, leukaemia and lymphomas, central nervous system (CNS) tumours, Wilms' tumour, retinoblastoma, neuroblastoma, hepatoblastoma, rhabdomyosarcoma, bone and soft tissues tumours, germ cell tumours, as well as specific histological types of leukaemias, lymphomas or CNS tumours. No strong association between maternal smoking in pregnancy and/or exposure to ETS and childhood cancer is found. Yet, several studies found slightly increased relative risks, generally smaller than 1.5, i.e. the order of magnitude associated with some recognized hazards of exposure to ETS (1.2 to 1.3 for adult lung cancer and cardiovascular diseases). Tumours most often found associated with maternal smoking in pregnancy or ETS exposure are childhood brain tumours and leukaemia-lymphoma, with risks up to two or greater in selected studies. In a few studies, risks associated with paternal smoking are higher than the maternal ones. This evidence from human studies coupled with demonstration ofgenotoxic effects on the foetus of exposure to metabolites of tobacco smoke, and demonstrable presence of adducts should lead to strong recommendations aiming at fully protecting foetuses, new-borns and infants from tobacco smoke.
Perinatal sidestream cigarette smoke exposure and the developing pulmonary surfactant system in rats
Authors: Subramaniaml Sriram , Srinivasan Suseela , Bummer Paul M , Gairola C Gary
Published: April 2003

1 Epidemiological studies have strongly implicated passive smoking with increased incidence of various respiratory diseases in children. Our earlier studies have shown that chronic exposure to tobacco smoke significantly changes the composition and the surface activity of the pulmonary surfactant in adult rats. The aim of the present study was to determine if perinatal exposure to sidestream cigarette smoke influences the composition and function of pulmonary surfactant system in developing rat pups. 2 Pregnant Sprague Dawley rats were exposed to sidestream cigarette smoke in a whole body exposure chamber for a total of 6 h each day and the pups born to these dams were further exposed to sidestream smoke for 2 h/day during postnatal period. Exposure of animals to smoke was ascertained by measuring their plasma cotinine. Surfactant analysis was performed on bronchoalveolar lavage fluids (BALF) collected from pups on postnatal day 1, 3, 7, 14, 21 and 35. The phospholipid (PL) content, percentage disaturated phosphatidylcholine (DSPC) and surfactant proteins (SP-A and SP-B) in BALF surfactant preparations from sham and smoke-exposed pups were compared. 3 Significant differences between the two groups were observed at two exposure points: a reduced level of SPA on day 1, and, a higher level of SP-A and PLs on day 21, in smoke-exposed pups. Surface activity analysis of the surfactant films by pulsating bubble surfactometer did not show any significant differences between the sham and smoke-exposed groups at any exposure point. 4 The results indicate that perinatal exposure to sidestream smoke is capable of producing biochemical changes in the composition of pulmonary surfactant at different stages of development but these changes do not influence surface tension reducing properties of the surfactant.
The experimental investigations of the toxic influence of tobacco smoke affecting progeny during pregnancy
Authors: Florek Ewa , Marszalek Andrzej , Biczysko Wieslawa , Szymanowski Krzysztof
Published: April 2003

1 Tobacco smoke contains around 4000 substances, most of which are described as toxic, and they may have an influence on the development of progeny. 2 The present studies concentrate on the measurement and calculation of indices describing the new-born' survival, rearing of pups, weight of foetuses, young animals, placenta and females in relation to different doses of tobacco smoke (carbon monoxide levels). The morphological studies of placenta, foetal and newborn lungs were done as a supplement. Biochemical placenta study was also done. 3 The results of the experiment proved that some indices for animals in groups which were passively exposed to the highest concentrations of tobacco smoke were lower, others fluctuated (4 day, 12 day and total survival) and some did not reveal any changes (rearing). Direct correlation between maternal passive exposure to tobacco smoke and the presence of acute respiratory distress syndrome symptoms in new-boms was observed. A decrease of body weight of pregnant females passively exposed to tobacco smoke was also observed. An increase of placenta-foetal factor was found. A decrease of rat weight was observed after passive exposure to tobacco smoke. 4 We concluded that there is correlation between passive exposition to tobacco smoke during pregnancy and delayed lung maturation in the offspring. Exposure of the pregnant rats to cigarette smoke increases the activity of isocitric and glucose-6-phosphate dehydrogenases in placenta.
Maternal passive smoking during pregnancy and fetal developmental toxicity. Part 1: gross morphological effects
Authors: Nelson Ed , Jodscheit Karin , Guo Yuanjian
Published: April 2003

1 Prenatal exposure of human fetus to tobacco smoke through maternal passive smoking has been epide-miologically linked to reduced birth weight, enhanced susceptibility to respiratory diseases and changes in immune system. However, no data exists indicating teratogenicity of involuntary smoking. Since sidestream smoke of cigarettes makes the most constituent of whole smoke inhaled by nonsmokers, we performed experiments to determine whether passive inhalation of sidestream smoke by rats causes malformations in newborns. 2 Pregnant 230-300 g Wistar rats were each placed in a 150 dm3 glass chamber with two holes, each 3 cm in diameter in two opposite walls to provide unforced exchange of fresh air. A third hole was connected to an automatic smoking machine. The head of a commercial filter blond cigarette (13 mg Tar, 0.9 mg Nicotine) was introduced to the chamber through this later hole. Cigarettes were smoked by smoking machine at the rate and volume resembling human smoking and the mainstream smoke was separately collected and discarded. Each rat thus received the sidestream smoke self-diluted in the chamber air. Experiments were performed with either 1, 2, 3 or 4 cigarettes/day during either first, second or third week of a total 21-day pregnancy period. The interval between smoking of cigarettes was 2 h. 3 COHb in blood of negative controls was about 1.2% and after exposure to 1 or 4 cigarettes were 6% and 12.2%, respectively. A dose-dependent reduction of birth weight was observed in newborns (P<0.001); bitem-poral diameters and body lengths were reduced accordingly. No macroscopically visible gross anomaly could be observed. After removing the fat tissue and staining the skeleton with alizarin, a widespread ossification retardation could be observed in all exposed groups regardless of the dose. Such a retardation was not limited to a particular bone. 4 These results support epidemiologic data on developmental toxicity of passive smoking and further provide evidence on an unfavorable osteopathic effect of sidestream exposure of mother on fetal development.
Passive smoking and pregnancy outcome in central Poland
Authors: Hanke W , Kalinka J , Florek E , Sobala W
Published: April 2003

1 The present investigation was undertaken to evaluate the effect of environmental tobacco smoke (ETS) on the risk of preterm delivery (PD) and small-for-gestational age (SGA) infants in a female non-smoking population of central Poland. 2 The study group were 1751 women classified as non-smokers in the comprehensive project on 'ocio-economic and environmental risk factors of preterm delivery and small-for-gestational-age babies in cen-tral Poland' conducted on a randomly selected population of 2080 women who gave birth to a child between June 1, 1996 and May 31, 1997. The PD group comprised 95 non-smoking women who delivered before 37 weeks of pregnancy and the SGA group included 111 non-smoking mothers of babies with birthweight below the loth percentile of the standard curves for central Poland. Passive exposure to tobacco smoke was determined based on a structured interview. 3 In the stepwise multiple logistic regression model maternal passive smoke exposure lasting 7 h or more was found to be a significant risk factor for preterm delivery. No significant effect of passive smoking on the risk of SGA was observed. 4 The information about the adverse effects of ETS exposure on pregnancy duration and outcome should be incorporated in the health promotion programmes for women.