Effect of Short—Term Exposure to Mercuric Chloride on the Air—Breathing Catfish,Heteropneusted fossilis

Histopathological effects of sublethal(0.1,0.2,0.3ppm)and lethal (0.5,1.0ppm)solutions of mercuric chloride(HgCl2)have been studied on the gills of the air breathing catfish,Heteropneustes fossilis at the intervals ranging from 6h to 15 days.Thickening of the epithelium,swelling and hyperplasia of the mucous cells,fusion of secondary lamellae,formation of interlamellar bridge and eposition of mucous over the entire surface are some noteworthy features of mercury poisoning in sublethal concentrations.Acute pathological manifestations are formation of formation of subepithelial space,sloughing of the epithelial layer,hemorrhage and hypertrophy of the mucous cells.Causes and impact of these cellular alterations affecting survival of the fish have been discussed.     

Modified sternal elevation for children with pectus excavatum

Objective To investigate the relationship between intestinal mucus IgA content and mucus barrier function after surface burns. Methods Detection of IgA content in mucus was performed by enzyme linked immunosorbent assay (ELISA) at different time points after burns.Bacterial adherence to cultured epithelial cells (IEC-6) in vitro using E.coli was assessed for each group. Results The intestinal mucus barrier function declined, parallel to a decrease in IgA content after surface burn in mice.In the normal control group, mucus IgA content was 2.32 Dλ, and 2.51, 1.76, 1.49, 1.06 Dλ at 0.5 h, 1 h, 6 h and 24 h after burn, respectively.Bacterial adherence rate was 0.53 in control group, and 0.46, 0.69, 0.58, 0.81 at 0.5 h, 1 h, 6 h, 24 h after burn, respectively. Conclusion The decrease of intestinal mucus IgA contents is one of the reasons why intestinal mucus barrier function declines after burns.     

Estimation of Acute Toxicity of Ammonium Sulphate to the Fresh—Water Catfish,Heteropneustes fossilis——Ⅱ.A Histopathological Analysis of the Epidermis

The toxicity of 4000 ppm(96h LC50 value)of the inorganic fertilizaer ammonium sulphate on the epidermis of Heteropneustes fossilis(H.fossilis)at different intervals of time has been studied.The destruction induced by the ammonium salt is massive.Secretion of a copious amount of slime from the goblet mucous cells leading to their exhaustion and/or shedding and subsequent disappearance is perhaps the first reaction to the toxicity of the irritant.Later,the polygonal epithelial cells of the outermost layer show cyclic stages of necrosis and sloughing followed by their regeneration and repair.The contents of the club cells show enormous shrinkage and condensation with subsequent replacement of their areas with a hazy substance.In the earlier stages of exposure,regeneration takes place quickly,side by side with the degenerative changes at different stages of experimentation.Later after 8 50 10d,the degenerative changes slow down and the epideris appears identical to that of the normal skin.Goblet mucous cells also showed several cyclic increases followed by decreases in number and activity.     

Damage to Hippocampus of Rats after Being Exposed to Infrasound

Objective The objective was to observe damage of hippocampus in rats after exposure to infrasound, and to assess HSP70 expression in hippocampus.
Methods SD rats in the experimental group were exposed to 140 dB (8 Hz) infrasound for 2 h per day for 3 days. The morphology of the hippocampus was examined by transmission electronic microscopic (TEM). Cell apoptosis was observed by TUNEL staining at 0 h, 24 h, 48 h, and 2 w after exposure. HSP70 expression was detected by immunohistochemistry (IHC) and Western blotting (WB).
Results TEM showed that hippocampus was significantly damaged by exposure, and exhibited recovery 1 week after exposure. The TUNEL data showed that neuronal apoptosis after exposure was significantly higher than in the control rats at 24 h and 48 h, and the apoptotic cells decreased one week after exposure. IHC and WB showed HSP70 expression was significantly higher in the exposed rats, peaked at 24 h.
Conclusion Exposure to 140 dB (8 Hz) infrasound for 2 h per day for 3 days appeared to induce damage to the hippocampus of rats, based on changes in ultrastructure and increased cell apoptosis. However, recovery from the damage occurred overtime. HSP70 expression also increased after the exposure and decreased by 48 h.     

Acute inhalation toxicity study of 2-fluoroacetamide in rats

One of the most potent rodenticides is 2-fluoroacetamide)2-FA).Toxicity of this chemical is well documented.However,its inhalation toxicity data is not available in the literature.Hence,acute inhalation toxicity study was carried out by exposing male and female rats to aerosols of 2-FA at different concentrations for 4h in a dynamically operated whole body inhalation exposure chamber.During and after the inhalation exposure the rats were less active,and showed mild tremors and convulsions.At higher concentrations the rats died after2-3 days.The estimated 4-h LC50 for male and female rats was 136.6 and 144.5mg.m^-3 respectively.Exposure to 0.7 LC50 for 4h duration showed an increase in the liver weight of male and female rats 7 days after exposure.Various haematological and biochemical variables determined were within the normal limits.Howerver,histological findings showed injured lung as indicated by desquamtion and necrosis of the epithelium of the respiratory tract.Marked hypertorphy of hepatocytes displaying strong acidophilic granulated cytoplasm was observed.Focal dilatation of renal proximal tubules in kidney with cytoplasmic vacuolation,and irregularly placed pyknotic nuclei were seen.The present study shows that 2-FA is a highly toxic chemical through the inhalation route based on the LC50 value.Consequently necessary precautions should be taken during its handling.     

Voltage-gated potassium channel Kv1.3 in rabbit ciliary epithelium regulates the membrane potential via coupling intracellular calcium

Background The cell layer of the ciliary epithelium is responsible for aqueous humor secretion and maintenance. Ion channels play an important role in these processes. The main aim of this study was to determine whether the well-characterized members of the Kvl family （Kv1.3） contribute to the Kv currents in ciliary epithelium. Methods New Zealand White rabbits were maintained in a 12 hours light/dark cycle. Ciliary epithelium samples were isolated from the rabbits. We used Western blotting and immunocytochemistry to identify the expression and location of a voltage-gated potassium channel Kvl.3 in ciliary body epithelium. Membrane potential change after adding of Kvl.3 inhibitor margatoxin （MgTX） was observed with a fluorescence method. Results Western blotting and immunocytochemical studies showed that the Kv1.3 protein expressed in pigment ciliary epithelium and nonpigment ciliary epithelium, however it seemed to express more in the apical membrane of the nonpigmented epithelial cells. One nmol/L margatoxin, a specific inhibitor of Kv1.3 channels caused depolarization of the cultured nonpigmented epithelium （NPE） membrane potential. The cytosolic calcium increased after NPE cell depolarization, this increase of cytosolic calcium was partially blocked by 12.5 μmol/L dantrolene and 10 μmol/L nifedipine. These observations suggest that Kv1.3 channels modulate ciliary epithelium potential and effect calcium dependent mechanisms. Conclusion Kv1.3 channels contribute to K＋ efflux at the membrane of rabbit ciliary epithelium.     

MORPHOLOGIC CHANGES IN THE BRONCHIOLAR EPITHELIA OF RATS EXPOSED TO VOLCANIC ASHES

This study reports the quantitative,and qualitative changesin the small airways after exposure to volcanic ash and quartz,and fol-lowed by an additional nine months of clean air.Three matched groupsof 75 rats were exposed to volcanic ash,quartz,and clean air in a Ro-chester exposure chamber 6 hours daily for 14 days.Animals were sac-rificed and studied,at pariodic intervals.Morphologic and morphometricevaluations were made using light microscope,transmissional electron mi-croscope and scanning electron microscope.The results showed:a.volcanicash produced the same damage in the small ailway as quartz did but lesssevere,b.Clara cells were the most severely damaged cell type occuringmost often at the end of exposure,and c.the damaged epithelial cellsmight be repaired by means of proliferation and differentiation of re-maining Clara cells,and perhaps type Ⅱ cells and Clara cells couldtransform mutually,and d.peribronchiolar fibrosis was greater after3 month exposure which may be persistent.These evidences indicate the exposure to either quartz or volcanic ashhas a persistent fibrogenic effect on the small airways in rats,butbronchiolar epithelium can be repaired as the stimulus is terminated.     

Effects of chloramphenicol preconditioning on oxidative respiratory function of cerebral mitochondria in rats exposed to acute hypoxia

To investigate the roles of chloramphenicol (CAP) preconditioning in the oxidative respiratory function of cerebral mitochondria in rats exposed to acute hypoxia during acute hypoxia by observing the changes of mitochondrial oxidative respiratory function and cytochrome C oxidase (COX) activity. Methods: Adult male Wistar rats were randomly divided into 4 groups: control (C), medication (M), hypoxia (H), and medication plus hypoxia (MH). Rats in groups M and MH were administered by peritoneal injection of CAP (50 mg/kg) every 12 h for 7 d before decapitation, but those in groups H and MH were exposed to a hypobaric chamber simulating 5 000 m high altitude for 24 h. The rat cerebral cortex was removed and mitochondria were isolated by centrifugation. Mitochondrial respiratory function and COX activity were measured by Clark oxygen electrode. Results: Compared with Group C, Group H showed significantly elevated state 4 respiration (ST4), decreased state 3 respiration (ST3), and respiratory control rate (RCR) in mitochondrial respiration during acute hypoxic exposure. ST3 in Group MH was significantly lower than that in Group C, but was not significantly different from that in Groups H and M, while ST4 in Group MH was significantly lower than that in groups C and H. RCR in Group MH was higher than that in Group H, but lower than that in Group C. COX activity in Group H was significantly lower than that in Group C. In Group MH, COX activity increased and was higher than that in Group H, but was still lower than that in Group C. Conclusion: Acute hypoxic exposure could lead to mitochondrial respirator3 dysfunction, suggesting that CAP preconditioning might be beneficial to the recovery of rat respiratory function. The change of COX activity is consistent with that of mitochondrial respiratory function during acute hypoxic exposure and CAP-administration, indicating that COX plays an important role in oxidative phosphorylation function of mitochondria from cerebral cortex of hypoxic rats.     

Simvastatin attenuates lipopolysaccharide-induced airway mucus hypersecretion in rats

Background Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases. This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide （LPS）. Methods Mucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS. Rats treated with or without LPS were administered intra-peritoneally simvastatin （5 and 20 mg/kg） for 4 days. Expression of Muc5ac, RhoA and mitogen-activated protein kinases （MAPK） p38 in lung were detected by real-time polymerase chain reaction （PCR）, immunohistochemistry or Western blotting. Tumor necrosis factor （TNF）-α and IL-8 in bronchoalveolar lavage fluid （BALF） were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay （ELISA）. Results Simvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung （P 〈0.05）. Moreover, simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-α and IL-8 in BALF follows LPS stimulation （P 〈0.05）. The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression, neutrophil accumulation and inflammatory cytokine release. Simultaneously, the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung （P 〈0.05）. Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation （P 〈0.05）. However, the increased expression of p38 protein in LPS-treated lung was not affected by simvastatin administration. Conclusions Simvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS. The inhibitory effect of simvastatin on airway mucus hypersecretion may be through, at least in part, the suppression of neutrophil accumulation and     

THE RECOGNITION OF UV-IRRADITION MELANOCYTE WITH HMB-45 MONOCLONAL ANTIBODY

Monnclonal antibody HMB-45 was previously thought to be melanoma specific antibody and was taken recently as a marker for melanocyte proliferation or activation. A single UV-irradiation system which may induce a functional activity change in melanocytes was used to test the irradiated epidermal melanocyte for expression of HMB-45.Melanocytes, in the epidermis of the biopsies taken 7 days after a single UV exposure, showed markedly stained HMB-45,accompanied by morphological changes such as enlarged size,rich cytoplasma and elongated dendrites. We conclude that since morphological changes in irradiated melanocytes may be interpreted as signs of functional activity changes, melanocytes are exposed to sthnulatory factors induced by UV light and get into a functional activating state to produce melanosome and HMB-45 antigen. Besides, the presence of HMB-45 in a single UV exposed epidermal melanocyte may support the hypothesis that its expression is inducible and is closely related to the functional activity     

Induction of heme oxygenase-1 in human hepatocytes to protect them from ethanol-induced cytotoxicity

We investigated the relationship between ethanol exposure and heme oxygenase (HO-1) in human hepatocytes in order to ascertain if induction of HO-1 can prevent ethanol induced cellular damage. Methods Dose-dependent (25-100 mmol/L) and time-dependent (0-24 h) ethanol exposure were used in the present study. HO-1 mRNA and protein expression were detected by PT-PCR and Western blot respectively. HO-1 activity was indicated by bilirubin and Fe^2 formation. Cytotoxicity was investigated by means of lactate dehydrogenate (LDH) and aspartate transaminase (AST) level in culture supematants, as well as the intracellular formation of malondialdehyde (MDA), cellular glutathione (GSH) status and CYP 2El activity. Results We first demonstrated a dose-dependent response between ethanol exposure and HO-1 mRNA and protein expression in human hepatocytes. We further observed a time-dependent increase of HO-1 mRNA expression using 100 mmol/L ethanol starting 30 minutes after ethanol exposure, reaching its maximum between 3 h and 9 h, Being similar to what had been demonstrated with the mRNA level,increased protein expression started at 6 h after ethanol exposure, and kept continuous elevated over 18 h. In addition, we found that ethanol exposure to hepatocytes markedly increased HO-1 enzyme activity in a time-dependent manner measured as bilirubin and Fez formation in human hepatocytes.Our results clearly showed that ethanol exposure caused a significant increase of LDH, AST, and MDA levels, while the antioxidant GSH was time-dependently reduced. Furthermore, we demonstrated that pre-administration of cobalt protoporphyrin (CoPP) induced HO-1 in human hepatocytes, and prevented an increase of MDA and a decrease of GSH. These effects could be partially reversed by zinc protoporphyfin (ZnPP), an antagonist of HO-1 induction. Conclusion HO-1 expression in cells or organs could lead to new strategies for better prevention and treatment of ethanol-induced oxidative damage in human liver.     

Progress of experimental study on treatment of psoriasis by Chinese medicinal monomer and single or compound recipe in Chinese materia medica

Psoriasis is a common,chronic,recurrent inflammatory skin disorder whose etiology is still unknown.It is believed that a multiple-gene inheritance is involved and it also involves various factors such as immunity,inflammation,cell proliferation,apoptosis,neural media,etc.Since cytokines are key mediators in inflammation,a number of Chinese medicines(CMs)have been reported to have certain antagonist effects on pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α),platelet active factor(PAF)and interleukin-8(IL-8).Some researches on CMs have made significant breakthroughs in psoriasis by intervening with cytokines.Abnormalities with keratinocyte proliferation and apoptosis are considered to be present in patients with psoriasis and a number of studies show that the mechanism of CMs on psoriasis may be through the inhibition of the keratinocyte proliferation and induction of apoptosis.Other studies also show that the inhibition of fibroblast-secreted cytokines could regulate keratinocyte proliferation and differentiation and reduce the level of Calcitonin gene-related peptide(CGRP)in plasma and in lesions so as to slow down the process of inflammation and proliferation in psoriasis.The most commonly used models for psoriasis are the scaled tails or the vaginal epithelium of mice in China.They were used to observe the histopathological changes after the model mice were treated with CMs with the inhibition on the mitosis of vaginal epithelium or promotion of granular layer in rat tail taken as the indices of clinical efficacy.A variety of signs occur in psoriasis patients with TCM blood-stasis syndrome type and the effect of CMs in activating blood circulation to remove blood stasis on psoriasis suggested that the mechanism of CMs may be partially correlated to hemorrheology and microcirculation.Along with the continuous development of the biosciences,some TCM theories for psoriasis have been confirmed by laboratory studies.However,the exploration into traditional Chinese medicines'biomechanics in psoriasis and the therapeutic mechanism of CMs by integrative medicine still requires further studies.     

Enzymatic and Ultrastructural Studies in a Freshwater Catfish: Impact of Methyl Parathion

Exposure to a sublethal concentration of methyl parathion (MEP) reduced the activity of cytoplasmic malate dehydrogenase. mitochondrial malate dehydrogenase, and lactate dehydrogenase by 30 to 49% in the liver and the skeletal muscle of the freshwater catfish, Clarias batraclms, after 7 days. The activities then began to recover and reached the control levels on the 28th day of MEP exposure. A complete recovery occurred on the 7th day when MEP was withdrawn from the medium after an exposure for 1 week. The withdrawal-dependent recovery in the activities was inhibited partially or completely by actinomycin Dandcycloheximide, suggesting de nova synthesis of the enzymes during the recovery period. A conjoint treatment of MEP and triiodolhyronine (T_3) restored the activities to control levels, indicating T_3 protection against the pesticide toxicity. SDS-PAGE of the cytoplasmic fraction of the liver showed some noticeable changes in the protein pattern after an exposure to MEP. Ultrastructural studies on MEP-treated liver cells showed disappearance of the glycogen granules and appearance of numerous smooth endoplasmic reticulum, lysosomal dense bodies, and swollen mitochondria. These changes in the liver are an indication of hepatic toxicity leading toward necrosis.(c) 1990 Academic Press.Inc.     

Proto-oncogenes expression in the process of asthma airway remodeling

Objective: To observe the expression of proto-oncogenes in the process of airway remodeling in asthma. Methods: Guinea pig was used as an asthma model challenged by ovoglobulin. Dot-blot, Northern-blot molecular hybridization and immunohistochemistry techniques were used to detect the expression of c-fos, c-myc, c-jun and c-sis. Results: Expression of c-fos and c-myc mRNA could not be detected or detected at very low level in the control group. There were greatly increased expression of c-fos and c-myc mRNA after guinea pigs were challenged by ovoglobulin. Thirty minutes after the challenge, the expression of c-fos and c-myc mRNA reached to the peak and returned to normal level 4 h after the challenge. Immunohistochemistry studies showed that Fos, Myc, Jun and Sis expressed at low level in control group and increased after ovoglobulin stimulation. Immunohistochemically positive cells laid in the plasma of airway epithelium, in cell nucleus of bronchial epithelium and in the inflammatory cells. Pathologic     

Immune responses to trichloroethylene and skin gene expression profiles in Sprague Dawley rats

Objective To characterize the immune reaction in SD rats exposed to trichloroethylene （TCE） and to identify the gene expression profiles involved in skin after TCE exposure. Methods Fifteen percent of TCE was injected intradermally into the rat back （100 μL/120 g） at intervals of 7 days. Whole blood was collected 24 h after the fifth or seventh intradermic administration of TCE. The percentages of CD4＋ and CD8＋ of T lymphocytes were measured by a flow cytometer. The concentrations of IFN-gamma and 1L-4 in the serum were semi-quantified by ELISA. Total RNAs of skin samples at 3 h or 24 h after the seventh dose of TCE in SD rats were extracted, and gene expression proftles of these tissues were analyszed by rat toxicology U34 array of Affymetrix. Results Obvious decline of CD4＋ in T lymphocytes was observed in the TCE-administer group. No significant concentration differences in IFN-gamma and IL-4 were found between TCE-treated and control rats. Gadd45a and Mel were significantly up regulated in skin tissue 24 h after TCE exposure. The expression regulation of immune response factors was as active as proteins associated with lipid metabolism and synthesis process in these skin samples of SD rats exposed to TCE. Conclusion T-helper type 1 cells mediate immune response can not be elicited in TCE-treated SD rats, but certain immune disorder can be induced.     

Effect of gamma irradiation on nuclear factor—kappa B in cultured bone marrow stromal cells

Objective: To explore the effect of gamma irradiation on nuclear factor-kappa B in cultured bone marrow stromal cells. Methods: Immunocytochemistry, Western blot and electrophoretic mobility shift assay (EMSA) were used. Results: The expression of NF-kB in cultured mouse bone marrow stromal cells (BM-SCs) on the level of protein was elevated after exposure to 60Co in the dosage of 8. 0 Gy with the use of im-munocytochemistry and Western blot. The activity of nuclear factor-kappa B in cultured BMSCs was significantly increased after exposure to gamma irradiation by using EMSA. The activity peak was at the 4th h after irradiation. Conclusion: Our results suggest that the activation of nuclear factor-kappa B in the BMSCs after irradiation may be involved in the protection of BMSCs against apoptosis and in the recovery of hematopoiesis after radiation.     

Changes of Tumor Necrosis Factor, Surfactant Protein A, and Phospholipids in Bronchoalveolar Lavage Fluid in the Development and Progression of Coal Workers’ Pneumoconiosis

INTRODUCTION Coal workers’ pneumoconiosis (CWP) is characterized by interstitial pulmonary fibrosis induced by inhalation of coal dust. Pneumoconiosis is traditionally diagnosed on the basis of a known exposure history, altered chest radiographs, and pulmonary malfunction. However, the use of these methods is limited in the diagnosis of early pneumoconiosis because fibrotic changes are usually manifested after a long latency process of inflammation and tissue impairment leading to clini…     

Detrimental Effect of Electromagnetic Pulse Exposure on Permeability of In Vitro Blood-brain-barrier Model

Objective To study the effect of electromagnetic pulse (EMP) exposure on permeability of in vitro blood-brain-barrier (BBB) model. Methods An in vitro BBB model, established by co-culturing brain microvascular endothelial cells (BMVEC) and astroglial cells (AC) isolated from rat brain, was exposed to EMP at 100 kV/m and 400 kV/m, respectively. Permeability of the model was assayed by measuring the transendothelial electrical resistance (TEER) and the horseradish peroxidase (HRP) transmission at different time points. Levels of BBB tight junction-related proteins were measured at 0, 1, 2, 4, 8, 12, 16, 20, 24 h after EMP exposure by Western blotting. Results The TEER level was lower in BBB model group than in control group at 12 h after EMP, exposure which returned to its normal level at 24 h. The 24 h recovery process was triphasic and biphasic respectively after EMP exposure at 100 kV/m and 400 kV/m. Following exposure to 400 kV/m EMP, the HRP permeability increased at 1-12 h and returned to its normal level at 24 h. Western blotting showed that the claudin-5 and ZO-1 protein levels were changed after EMP exposure. Conclusion EMP exposure at 100 kV/m and 400 kV/m can increase the permeability of in vitro BBB model and BBB tight junction-related proteins such as ZO-1 and claudin-5 may change EMP-induced BBB permeability.     

Radiation hormesis in relation to radiation protection.

A radiation-induced adaptive response has been convincingly demonstrated in a variety of cultured cells. It is associated with the activation of genes and the up-regulation of protein enzymes, resulting in a delay in cell-cycling and the opportunity to repair radiation-damaged DNA as a transient phenomenon. Just how the adaptive response operates in a multi-cellular organism is still obscure, but there is little or no evidence in rodents and the beagle dog of a shortening of lifespan after exposure to acute doses up to a few hundreds of mGy or after chronic daily exposure resulting in accumulated doses of up to a few Gy. Nevertheless there is an increase in both non-neoplastic and neoplastic diseases which need not be life-threatening. A prudent approach has been used by the 1CRP in deriving a value for radiation-induced detriment at low doses from which to recommend individual dose and risk limits in their system of radiological protection. This is not to deny the possible existence of an adaptive respo     

Acute Toxicity and Cardio-Respiratory Effects of 2-Deoxy-D-Glucose： A Promising Radio Sensitiser

Objective To evaluate the acute toxicity of 2-deoxy-D-glucose （2DG） by oral （p.o.） and intravenous （i.v.） routes, and also the cardio-respiratory effects following high doses of 2DG in animal models. Methods The LD50 of 2DG （in water） was determined in rats and mice by p.o. route and in mice by i.v. route. The effect of 2-DG （250 mg/kg, 500 mg/kg, and 1000 mg/kg, i.v.） was studied on various cardio-respiratory parameters viz., mean arterial blood pressure, heart rate and respiratory rate in anaesthetised rats. The effect of 2DG （500 mg/kg, 1000 mg/kg, and 2000 mg/kg, p.o.） was also studied on various respiratory parameters viz., respiratory rate and tidal volume in conscious rats and mice using a computer program. Results The p.o. LD50 of 2DG was found to be 〉8000 mg/kg in mice and rats, and at this dose no death was observed. The LD50 in mice by i.v. route was found to be 8000 mg/kg. At this dose 2 out of 4 mice died and the death occurred within 6 h. A significant increase in the body weight was observed after p.o. administration of 2DG in rats at 500 mg/kg, 1000 mg/kg, and 2000 mg/kg doses. There was no significant change in the body weight at 4000 mg/kg and 8000 mg/kg by the p.o. route in rats and up to 8000 mg/kg by p.o. as well as i.v. routes in mice. Intravenous administration of 2DG （250 mg/kg, 500 mg/kg, and 1000 mg/kg） in anaesthetised rats showed a time-dependent decrease in the mean arterial blood pressure. There was no change in the heart rate in any of the treatment groups. The tidal volume was not changed significantly by p.o administration in conscious rats, but a significant decrease in the respiratory frequency at 500 mg/kg and 1000 mg/kg doses was observed. In the mice also there was no change in the tidal volume after p.o, administration, but the respiratory frequency decreased significantly at 2000 mg/kg dose. Conclusion 2DG is a safe compound but can cause a fall in the blood pressure and a decrease in respiratory frequency at high doses.