A combined effect of the nitrogen dioxide and sodium nitrite on the rat organism

A combined effect of the nitrogen dioxide and sodium nitrite on the rat organism

220 Poster Session 4D. Inhalation Toxicology is frequently induced by chronic administration of a wide range of inhaled agents. Squamous metaplasia ...

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220

Poster Session 4D. Inhalation Toxicology

is frequently induced by chronic administration of a wide range of inhaled agents. Squamous metaplasia was induced at this site in the rat by chronic irthalation of pharmaceutical vehicles containing menthol. This study set out to confirm that menthol administered alone could alter the laryngeal epithelium. High resolution light microscopical evaluation was performed on samples of ventral larynx that were obtained at selected time points following exposure of rats to an acute irthaled dose of menthol. In addition, bromodeoxyuridine (BRDU) incorporation into DNA synthesising cells was also assessed. Results showed that inhalation of menthol induced selective injury and loss of ciliated epithelial cells soon after administration. This repaired by basal cell proliferation and mononuclear cell maturation into ciliated columnar epithelium to replace the lost cells. There was no consistent accompanying inflammatory cell infiltration although evidence of transient minimal squamous metaplasia was seen before return to normality by 28 days post exposure. The detection of a transitory metaplastic squamoid epithelium during repair may indicate that a chronic insult of a similar mild severity could induce a more permanent adaptive squamous metaplasia at this site.

I P4D73 I PROTECTION FROMCYTOTOXIC EFFECTS INDUCED BY MECHLORETRAMINE ON AJRWAY EPITHEUUM

S. Rappeneau *, A. Baeza, I. Giuliani, C. Jeulin, F. Marano. Laboratoire de Cytophysiologie et Toxicology Cellulaire, Universite Paris 7-Denis Diderot, 2 place Jussieu, 75 251 Paris cedex OS, France Mechlorethamine (HN2) is an alkylating agent effective in cancer chemotherapy but leading to severe side effects like lung complications. DNA strand breaks caused by HN2 hyperactivate the poly(ADP-ribose)polymerase (PARP) resulting in a rapid depletion of NAD+ and ATP. Moreover, studies on primary cultures of rabbit tracheal epithelial cells showed that HN2 early induced an oxidative stress. According to these knowledges on HN2 mode of action, the present study was realized to find protective molecules against HN2 toxicity. Different classes of protectors were studied: • molecules with antioxidant activity: - thiolsmolecules (N-acetylcysteine, WR-1065) or molecules which increase the intracellular pool of -SH (WR-272 1, N-acetylcysteine) - phenolic compounds (tocopherol, silymarin, butylhydroxytoluene) - iron chelators (O-phenanthroline, desferrioxamine) • PARP inhibitors: - niacinamide, 3-aminobenzarnide and phenanthridinone. Their protective effects were assessed by the use of differents tests on a bronchial cell line 16 HBE 140- . The MIT test was used to identify modifications in the metabolic activity of the cells treated for 4 h with 0.5 roM of HN2.The intracellular production of peroxides was mesured using a f1uorescente probe (DCFH-DA) and intracellular ATP level was determined by a bioluminescence assay. Results showed that only molecules having a free -SH group (NAC, WR-l065) and the PARP inhibitors were able to protect cell metabolism in immediate or differed cotreatments with HN2. Pretreaments were ineffective. The direct interaction between thiol molecules and electrophilic groups of HN2 as well as their antioxidant properties seem to explain their protection. The PARP inhibitors are able to inhibit the decrease of intracellular ATP pool induced by HN2. Thus, these results suggest that PARP is implicated in early toxic events induced by HN2. Supported I7y D.G.A (nO14503-07(22197).

IP4D74 I MOLECULAR MECHANISMS OF IL-8INDUCTlON BY TNF-a IN LUNG EPITHELIAL CELLS

P.P. Simeonova *, S. Leonard, M.1.Luster. NlO Sfl, Morgantown, wv. USA

INF-a is produced by variety of pulmonary cells, including macrophages, lymphocytes, mast cells and has been strongly implicated as a key mediator of the local pro-inflammatory cytokine network in the lung. TNF-a can stimulate rapid production of soluble chemotactic factors, including IL-8, which consequently results in significant chemotaxis of neutrophils across epithelial cell barriers. Such a mechanism may contribute to numerous lung diseases. We demonstrated that INF-a induces normal human bronchial epithelial cells as well as A549 cells, a prototype of type II epithelial cells, to secrete and express IL-8. The response occurs to be transcriptionally regulated, since INF-a activates CAT expression in pulmonary epithelial cells transfected with IL-8 promoter constuct, The - 99/- 66 fragment of IL-8 promoter, containing the binding sites for NF-kB and NF·lL-6 transcription factors is required for TNF-a-induction. TNF-a activates IL-8 expression in lung epithelial cells through INFRl, which is abundantly expressed in these cells. TNF-a stimulates ROS formation, measured as DMPO-OH adducts in lung AM as well as epithelial cells and consistent with the oxidative state modulation, antioxidants down-regulate NF·kBlNF-IL-6 dependent IL-8 transcription activation and the consequent IL-8 expression.

IP4D7S1 AN NITRICOXIDE INDUCED LUNG EMPHYSEMA: ASSESMENT BASED ON HISTOPATHOLOGICAL STUDIES IN SQUIRREL

A.L. Dahiya *1, P.N. Saxena. Toxicology Laboratory, Zoo logy Departm ent, Institute of Basic Sciences (Agra University) , Khandari Campus, Agra-282008 (U P.); (1present add: LAM3!7, School of Life Sciences, Jawaharlal Neh ru University, New Delhi-I /0067. India Nitrogen oxides are being in study for many years primarily as toxic air pollutants. Nitric oxide has been assigned as important bioactive species and is under extensive research due to its exogenous production from the combustion of fossils fuels and cigarette smoke and also Its endogenous formation inside bio-systems. In the present investigation squirrels were exposed (I hr/day) to atmospheres consisting nitric oxide concentration at 25 ppm and 35 ppm. Animals were sacrificed 24 hr after 5, 10, 20 exposures. Severe airway injury in present investigation is manifested by extensive sloughing and necrosis of endothelial cells. The histopathology revealed emphy sema-pathological abnormality resulting into alveolities. The concerned development is observed to increase with increased concentration of nitric oxide exposure and becomes severe on day 20 suggestive of toxic effect of gas in question resulting into a possible oxidant- antioxidant imbalance. Latter is further supported by the puffy appearance of macrophages and the inflammatory condition observed.

IP4D76 I

A COMBINED EFFECTOF THE NITROGEN DIOXIDE ANDSODIUM NITRITE ON THE RAT ORGANISM

N.P. Dmitrenko *, VA Ivanitsky, Y.Ya Varich, S.Y. Snoz. Institute of Ecohygiene and Toxicolo gy, Kyiv, Ukraine Male Wistar rats have been subjected to injection of NaN0 2 and two-hour irthalation of N02. A synergetic increase of the levels of the nitrite, nitrate, methemoglobin and hemoglobin-NO complex in the rat blood and hemoglobin-NO complex level in the rat liver were observed. The level of the oxidized form of the cytochrome P-450 in the rat liver decreased in a such way as if it were a separate injections of this substances.

Poster Session 4D. Inhalation Toxicology

The potentiation of a dangerous toxic effect of these ecological pollutants on the human organismhas been supposed.

I P4D77 I BLOOD PLASMASELENIUM CONCENTRATION AND GLUTATHIONE PEROXIDASE ACTIVITY IN BAL AND BLOODOF RATS EXPOSED TO NO.

1. Gromadziriska *, W. W~sowicz, K Rydzyriski, J. Neve", R. Swiercz. Institute ofOccupational Medicine, Lodz, Poland; 1 Free

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which represents the first part of the study is directed towards monitoring the sulphur dioxide levels due to compost manufacturing in Abu Dhabi Compost Plant. The most important finding reached through the investigation is the responsibility of the plant as a source of sulphur dioxide inside and outside it. The mean levels detected for the gas highly exceed the standards set for the two environments. Strong actions should be taken by the Authority responsible for this plant to manage the indoor and hence the outdoor air quality.

University ofBrussels, Belgium

The aim of this study was to investigate how different dietary Se intake may influencethe antioxidant status of rats exposed to NO,. Three groups of rats were fed a diet with different Se content for 16 weeks (ca. 1.3; 3.5; and 6.0 J-tg Se/day). Blood plasma Se concentration and erythrocyte glutathione peroxidase (GSH-Px) activity were monitored weekly during the study. After 12 weeks of feeding a half of the number of rats from each group were exposed to 5 ppm NO, for 4 weeks (6 h/day. It was found that plasma Se concentrations in all the exposed groups were lower than in controls (473 ± 73 J-tg/l vs. 548 ± 24 J-tg/l p. < 0.01; 364 ± 29 J-tg/l vs. 507 ± 86 J-tg/l, p. < 0.001, and 216 ± 38 J-tg/l vs. 250 ± 60 J-tg/l, NS, respectively). Erythrocyte glutathione GSH-Px activity in rats fed low-Se diet was significantly lower than in controls (26.6 ± 6.4 u1Hb vs. 38.6 ± 8.0 ulg Hb, P < 0.001). Bronchoalveolar lavage fluid (BAL) GSH-Px activity in rats fed rich-Se diet and exposed to NO, was at the similar level as in controls (21.1 ± 2.8 mu/ml vs. 20.3 ± 4.3 mu/ml) but in NO, exposed animals fed low-Se diet it was found to be significantly lower (14.9 ± 2.8 mu/ml vs 28.4 ± 0.9 mu/ml, p. < 0.001).

IP4D78 I ACID GASESIN THE ATMOSPHERE OF ABU DHABI CITY, UNITEDARAB EMIRATES

K T. Hindy *1 , S.P. AI-Wasity2. lAir Pollution Resarch Def,artment, National Resarch Centre, Tahrir St., Dokki, Cairo, Egypt; Ministry ofPublic Work and Housing, P.O. Box: 468 Abu Dhabi, United Arab Emirates The present investigation includes long-term measurements of S02 and NO, N02, and NOx in Abu Dhabi city. Those measurements were carried out during Winter and Spring of the two years 1991-1992 and 1992-1993. The sulphur dioxide and nitrogen oxides were measured by the Environment S.A. Mobile Laboratory. Through presenting and discussing the results of this investigation, it has been well acknowledged that: (a) S02 and NOx concentrations in the atmosphere of Abu Dhabi city are less than the U.S. NAAQS (30 ppb for S02 and 50 ppb for NOx), (b) There is a relatively strong inverse relationship between S02 and NOx concentrations and relative humidity levels in the atmosphere of Abu Dhabi city due to the conversion of S02 to H2SO4 and NOx to HN03, and (c) NOx in Abu Dhabi ambient air tend to be mainly in the form of N02 and to a lesser degree in the form of NO.

IP4D79!

AIR POLLUTION STUDY INDOOR AND OUTDOOR OF THE ABU DHABI COMPOST PLANT: I. SULPHUR DIOXIDE STUDY

KT. Hindy *1, J.E. AI Jabri2 . lAir Pollution Resarch Department, National Resarch Centre, Tahrir St., Dokki, Cairo, Egypt; 2 Food and Environment Control Centre. Abu Dhabi Municipality, Abu Dhabi. United Arab Emitrates Air pollution represents one of the major drawbacks of composting process. Air pollutants associated with such source include mainly sulphur dioxide, ammonia and methane. The present investigation

I P4D80 I A COMPARISON OF EFFECTS OF ACUTEAND SUBCHRONIC EXPOSURE TO S02

J. Suchankova* 1 , P. Visiiovsky 1 , V.Gersl2 , Z. Fiala. 1 Dept. Pharmacol. & Toxicol., Faculty of Pharmacy Charles University; 2 Faculty ofMedicine Charles University, Czech Republic

The present paper aims to compare the effects of acute and subchronic exposure to S02 on non-invasive cardiac parameters in guinea-pigs (changes in the values of non-invasive cardiac parameters, particularly the PEP vs. LVET ratio, reflect changes in the cardiac functional ability). In acute exposure to S02 (400 ppm, 3 hours), non-invasive cardiac parameters were examined 7 days prior to exposure and then either 3 or 24 hours after termination. In subchronic exposure to S02 (400 ppm, 3 hours a day, 28 days), measurements were made 7 days prior to the first day of exposure and then on days 7, 14, 21 and 28 of exposure (always 3 hours after terminationof exposure). This arrangementmade it possible to examine the development of the parameters under study during the experiment. In the same time intervals, measurementsof control animals exposed to the air were made. Measurements were performed in Ketamin narcosis (150 mg/kg) i.p. Results: In each time interval, S02-exposed animals were compared with controlsand the valuesobtainedbeforeand afterexposure. In an interval of 3 hours after acute exposure, no significant differences in the values of parameters under study were found. In an interval of 24 hours after acute exposure to S02, there existed a slight, but significant increase in the ratio of PEP vs. LVET, PEP and Q2, these values significantly differed from controls. During subchronic exposure to S02 there occurred an increase in the values of minute heart rate. In other parameters no significantchanges were found. Supported by grant of GA Charles University, Prague No. 30/95.

IP4D81 I CHEMILUMINESCENCE OF WHOLEBLOOD AND URINEOF THE WORKERS, WHO CONTACT WITH OZONE

N.E Abdrashitova *, EKh. Kamilov, L.Y.Krivochighina", Sh.Z. Zagidullin. Bashkir State University; I Chelyabinsk State Medical Academy, Russia

Sickness rate of the workers of undertakings straightly correlates with air pollutionof industrial premises with different oxidants from which ozone is the strongest. The aim of our investigation is the formation of Free Radicals in whole blood and urine of 148 workers of dialkilphtalates department, where ozone is the main component of the technical process. We registrated chemiluminesce (Cl.) with the help of portable device CL-003. We observed in 85% causes (length - 2 years) the rise of spontaneousluminolluminous of the capillary and venous blood in 85% causes in re-computation to one leucocyte up to 3--4 times. Metabolicactivity of phagocytes of whole blood of another group (15%) was lower, than in the control one. Spontaneous CL rose up to 6-7 times with increasing lenth of work. One of the most irnporrant characteristics of phagocytic cells is the ability for development respiratory "burst". The intensivity of respiratory "burst"of phagocyticcells in answer to zymozan decreased together