Introduction. The widely used antiarrhythmic amiodarone (AD) has been linked to many health problems, including pulmonary toxicity. The objective of the study. In the present study we assessed the protective effect of 21-aminosteroid U-74389 G due to its antioxidative and membrane-stabilizing potency on amiodarone-induced pneumotoxicity in rats. Material and methods. The study was carried out on 72 male Wistar rats, divided into four groups: (1) – control; (2) – treated with AD intratracheally; (3) – treated with AD and U-74389G; (4) – treated with U-74389G alone. AD was instilled twice on days 0 and 2 (6.25 mg/kg with a concentration 3.125 mg/mL). U-74389G was injected intraperitoneally on days 0, 1 and 2 in a dose of 5 mg/kg. The activity of super-oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GP), malondialdehyde (MDA) content and hydroxyproline content were performed on days 3, 7, 14 and 28 in lung homogenate. Hydroperoxide concentrations were measured in the plasma. Results. AD administration affected antioxidant defense system in the lungs, promoted lipid peroxidation, and caused pulmonary fibrosis. Conclusions. The 21-aminosteroid U-74389G significantly inhibited lipid peroxidation and mitigated fibrous changes in rat lungs provoked by AD.

Website: www.phcog.com DOI: 10.4103/0973-1296.131024 Quick Response Code: P H C O G M A G . O R I G I N A L A R T I C L E Valcheva-Kuzmanova, et al.: Effect of AMFJ in amiodarone-induced pneumotoxicity Pharmacognosy Magazine | April-June 2014 | Vol 10 | Issue 38 133 of the release of pro-infl ammatory cytokines such as tumor necrosis factor alpha and interleukins (interleukin IL-1 beta, IL-6, IL-8).[19,20] There are numerous pathologic similarities between human and rodent lungs and as such, rodent model presents an excellent tool to investigate pathologic changes in vivo.[21] The aim of the study was to investigate the effect of A. melanocarpa fruit juice (AMFJ) in a rat model of AD-induced pulmonary toxicity. MATERIALS AND METHODS Experimental substances AD hydrochloride and all other chemicals and reagents wereof analytical grade and were purchased from Sigma-Aldrich Company (Germany). The Quantikine Rat IL-6 and IL-10 immunoassay kits were from R and D Systems (USA). AMFJ was produced from A. melanocarpa Elliot fruits grown in the Balkan Mountains, Bulgaria. They were handpicked in September, crushed and squeezed. The juice was fi ltered, pasteurized at 80°C for 10 min and stored at 0°C until the experiment. The contents of phenolic substances in 100 mL AMFJ were: Total phenolics, 709.3 ± 28.1 mg as gallic acid equivalents, determined spectrophotometrically according to the Folin-Ciocalteu procedure;[22] total fl avonoids, 189.4 ± 8.6 mg as catechin equivalents, measured by a colorimetric assay developed by Zhishen et al.;[23] total anthocyanins, 106.8 ± 6.2 mg as cyanidin-3-glucoside equivalents, determined by a pH-differential spectrophotometry at pH 1.0 and pH 4.5;[24] quercetin, 11.8 mg, measured by a high-performance liquid chromatography method.[25] The values were the mean of duplicate determinations of three samples. Animals and experimental treatments The study was carried out on 96 male Wistar rats (weight 220-250 g, age 4 months). The animals were obtained from the Research and Laboratory Animal Breeding Center of Slivnitsa (Bulgaria) and were housed in the university animal quarters for 1 month at a temperature of 22°C ± 2°C and humidity of 50 ± 10%, given normal pelleted diet and water AD libitum. All procedures concerning animal treatment and experimentation were conducted in compliance with the national laws and policies, in conformity with the international guidelines (European Economic Community EEC Council Directive 86/609, IL 358, 1, December 12, 1987). The animals were divided into four groups of 24 rats. Each group was subdivided into four subgroups of six rats. One subgroup of each group was sacrifi ced on days 3, 5, 10, and 28 under thiopental anesthesia (50 mg/kg) after receiving the respective treatment in the course of 2, 4, 9, and 10 days, respectively. Group 1 (Control) received two intratracheal (i.t.) instillations of sterile distilled water (2 mL/kg) on days 0 and 2. The four subgroups of Group 1 received distilled water (10 mL/kg) orally through an orogastric cannula from day 1 to days 2, 4, 9, and 10, respectively. Group 2 (AD) received two i.t. instillations of AD (6.25 mg/kg, as a 3.125 mg/mL water solution) on days 0 and 2.[26] The subgroups of Group 2 received distilled water (10 mL/kg) orally through an orogastric cannula from day 1 to days 2, 4, 9, and 10, respectively. Group 3(AD + AMFJ5) was treated with AD i.t. on days 0 and 2, and from day 1 to days 2, 4, 9, and 10 the respective subgroups received AMFJ orally at a dose of 5 mL/kg diluted with distilled water to a total volume of 10 mL/kg. Group 4 (AD + AMFJ10) was treated with AD i.t. on days 0 and 2, and from day 1 to days 2, 4, 9, and 10 the respective subgroups received AMFJ orally at a dose of 10 mL/kg. AD was dissolved in distilled water at 60°C and allowed to cool to room temperature before the i.t. instillation. Lung weight coeffi cient The body weight and lung weight were measured for each animal. The lung weight coeffi cient (organ weight in mg/100 g body weight) was calculated. Bronchoalveolar lavage Bronchoalveolar lavage fl uid (BALF) was obtained on days 3, 5, and 10. Rats were sacrifi ced by exsanguination through cutting v. renalis. The chest was opened, and the lungs were perfused in situ via the right heart ventricle with saline (30 mL). Triple lavage of the left lung through the trachea with a total of 5 mL of saline was performed. The volume of fl uid recovered ranged from 80% to 90% of the fl uid introduced. Cytological assays of BALF One aliquot of the BAL F was used for total cell count ×105/L. The cells were removed by centrifugation at 300 × g for 10 min. The cell pellet was resuspended in 1 mL of saline. The cell differentials were analyzed using the procedure of Danos and Keebler, modifi ed by Saltini et al.[27] Cells were collected on nitrocellulose fi lters 25 mm in diameter with 5 μm pores (SWP-025-00 Catalogue number SMWP02500; Millipore Corp.) and were stained with H and E. Biochemical assays of BALF After centrifugation of BALF, the supernatant was used for the measurement of enzyme activities such as lactate Valcheva-Kuzmanova, et al.: Effect of AMFJ in amiodarone-induced pneumotoxicity 134 Pharmacognosy Magazine | April-June 2014 | Vol 10 | Issue 38 dehydrogenase (LDH), acid phosphatase (AcP), and alkaline phosphatase (AlP) by the methods of Bergmeyer et al.[28] Total protein content was measured by the method of Lowry et al.[29] The enzyme activities are represented in U/L, and total protein in mg/mL of BALF. Biochemical assays of lung homogenate Lung homogenate was obtained from the right lung. The tissue was homogenized with potassium chloride KCl (1.15%) in 1:10 ratio. The homogenate was centrifuged (9000 × g, 30 min), and the supernatant was stored on ice. Malondialdehyde (MDA) content i n nmol/g tissue was measured on days 3, 5, and 10 by the method of Ohkaw a et al.[30] Hydroxyproline (HP) levels (in μg/mL) were measured in lung homogenate of rats sacrifi ced on day 28 as described by Bergman and Loxley.[31] The method is based on the release of free HP from collagen by acid hydrolysis. Immunological assays of rat serum The serum of the experimental animals was used for the measurement of IL-6 and IL-10 in pg/mL on days 3, 5, and 10 by the ELISA method in accordance with the immunoassay kits manufacturer’s instructions. Statistical analysis Results are presented as mean ± SEM. The data were tested by one-way ANOVA, followed by Dunnett’s multiple comparison post-test to identify signifi cant difference. A level of P < 0.05 was considered signifi cant. All analyses were performed using GraphPad Prism Statistical Software.

Background: The fruits of Aronia melanocarpa (Michx.) Elliot is extremely rich in biologically active polyphenols. Objective: We studied the protective effect of A. melanocarpa fruit juice (AMFJ) in a model of amiodarone (AD)-induced pneumotoxicity in rats. Materials and Methods: AD was instilled intratracheally on days 0 and 2 (6.25 mg/kg). AMFJ (5 mL/kg and 10 mL/kg) was given orally from day 1 to days 2, 4, 9, and 10 to rats, which were sacrificed respectively on days 3, 5, 10, and 28 when biochemical, cytological, and immunological assays were performed. Results: AMFJ antagonized AD-induced increase of the lung weight coefficient. In bronchoalveolar lavage fluid, AD increased significantly the protein content, total cell count, polymorphonuclear cells, lymphocytes and the activity of lactate dehydrogenase, acid phosphatase and alkaline phosphatase on days 3 and 5. In AMFJ-treated rats these indices of direct toxic damage did not differ significantly from the control values. In lung tissue, AD induced oxidative stress measured by malondialdehyde content and fibrosis assessed by the hydroxyproline level. AMFJ prevented these effects of AD. In rat serum, AD caused a significant elevation of interleukin IL-6 on days 3 and 5, and a decrease of IL-10 on day 3. In AMFJ-treated rats, these indices of inflammation had values that did not differ significantly from the control ones. Conclusion: AMFJ could have a protective effect against AD-induced pulmonary toxicity as evidenced by the reduced signs of AD-induced direct toxic damage, oxidative stress, inflammation, and fibrosis.

The effect of Aronia melanocarpa fruit juice (AMFJ) on the activity of antioxidant enzymes in a model of amiodarone (AD)-induced pneumotoxicity in rats was studied. AD was instilled intratracheally on days 0 and 2 (6.25 mg/kg as a 3.125 mg/mL water solution). AMFJ (5 mL/kg and 10 mL/kg) was given orally from day 1 to days 2, 4 and 9. The activities of catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in lung tissue were measured on days 3, 5 and 10, respectively. AD decreased significantly CAT activity on days 3, 5 and 10. It caused a decrease of GPx activity which was significant on day 3. It decreased SOD activity but not significantly. AMFJ antagonized the effects of AD to such an extent that the enzyme activities at all time points did not differ significantly from the control values. The effect of AMFJ is probably due to its polyphenolic ingredients which serve as powerful radical scavengers. AMFJ probably decreased of the oxidative damage of cells by AD-induced overproduction of reactive oxygen species thus preserving the capacity of cells to produce antioxidant enzymes which, in turn, could further reduce oxidative stress.

The effect of Aronia melanocarpa fruit juice (AMFJ) on indices of inflammation and fibrosis was studied in a model of amiodarone (AD)-induced pneumotoxicity in rats. AD was instilled intratracheally on days 0 and 2 (6,25 mg/kg as a 3,125 mg/mL water solution). AMFJ (10 mL/kg) was given orally to rats either from day 1 to day 10, or from day 11 to day 27. Thus, the animal groups were: control, AD, AD+AMFJ (day 1-10), and AD+AMFJ (day 11-27). The rats were sacrificed on day 28. The levels of IL-6 and IL-10 were measured in rat serum as markers of inflammation, and hydroxyproline (HP) level was determined in lung tissue as a marker of fibrosis. AD caused a tendency to elevate IL-6 and decrease IL-10. AMFJ counteracted these effects of AD. In rats from group AD+AMFJ (day 1-10), IL-6 level was significantly lower (p<0,05) than that of AD group, lower (p<0,05) even than the control value. AD significantly increased (p<0,05) HP content in lung homogenate. AMFJ antagonized that effect, and in AMFJ-treated rats HP levels did not differ significantly from the control value. Any AMFJ effects were more prominent in rats that were treated with the juice during the first 10 days after AD instillation. In conclusion, AMFJ reduced the signs of inflammation and could have a protective effect against AD-induced pulmonary fibrosis, especially if administered in the early phase after AD instillation. Scripta Scientifica Medica 2012; 44(2): 37-40.

The effect of dexamethasone on some markers for cytotoxicity and proliferation in rat intestine after total body gamma irradiation was studied. Seventy-two male rats were divided into three groups: group 1 (controls); group 2 (receiving a single 6 Gy total body irradiation); group 3 (receiving dexamethasone and 6 Gy ionizing radiation). The animals in group 3 were injected i.p. with dexamethasone at a dose of 3 mg/kg four hours before irradiation, as well as on days 2 and 3 after exposure. The levels of IL-6 and CINC-1 were determined in the plasma by the ELISA method. Immunohistochemical and histological studies were performed in rat intestine. Ionizing radiation increased the levels of IL-6 and CINC1 considerably in comparison to that in controls on day 3. Dexamethasone significantly decreased the level of IL-6 on day 7, as compared to both controls and irradiated group. The level of CINC-1 in group 3 was significantly lower on days 3 and 7 than that in the control group. Immunohistochemical testing with the marker for proliferative activity Ki-67 in group 2 showed a total suppression of the proliferative activity, in contrast to the controls. In group 3, the same testing showed a decrease, though the activity was still present. Dexamethasone produced moderate anti-inflammatory protection from radiation injury.

Aim. To investigate the effects of MnTE-2-PyP on some markers of antioxidant defence system in asthma mice model. Material and Methods. The animals were divided into four groups: group 1, controls; group 2, injected with ovalbumin, group 3, treated with MnTE-2-PyP, and group 4, treated with ovalbumin and MnTE-2-PyP. The activities of superoxide dismutase, catalase, glutathione peroxidase and nonprotein sulfhydryl groups content (NPSH) were determined in lung homogenate. Results. The activities of superoxide dismutase and catalase in group 2 decreased significantly as compared to control group. The decrease of the same enzymes in group 4 was lower and significant as compared to group 2. Changes in the glutathione peroxidase activity showed a similar dynamics. The NPSH groups content decreased in group 2. In group 4 this decrease was relatively lower as compared to group 2. Conclusions. The application of MnTE-2-PyP mitigated the effects of oxidative stress in asthma mice model.

We aimed to study the MnTnHex-2-PyP effect on some markers of lung antioxidant defence system in mice asthma model.The study was carried out on 28 C57B1/6 mice divided into four treatment groups: group 1 - controls; group 2 - injected and inhaled with ovalbumin; group 3 - treated with MnTnHex-2-PyP and inhaled with phosphate buffered saline; group 4 - injected with ovalbumin and MnTnHex-2-PyP but also inhaled with ovalbumin. On days 24, 25 and 26, mice from groups 1 and 2 were inhaled with PBS for 30 min, and those from groups 2 and 4 were given a 1% ovalbumin solution. One hour before inhalation, and 12 hours later the animals from groups 1 and 2 were injected i.p. with 100 μl PBS, and those from groups 3 and 4 received a 100 μl MnTnHex-2-PyP solution in PBS, сontaining 0,05mg/kg. The animals were killed by exsanguination 48 hours after the last inhalation for obtaining a lung homogenate. The activities of superoxide dismutase, catalase, glutathione peroxidase and the non-protein sulphhydryl group content in the lung homogenate were investigated. Ovalbumin decreased the activities of superoxide dismutase (p=0.01), catalase (p=0.002), glutathione peroxidase and non-protein sulphhydryl groups content (p<0.001) in comparison to controls. In group 4 (ovalbumin and MnTnHex-2-PyP) the activities of superoxide dismutase (p=0.044), catalase (p=0.045), glutathione peroxidase (p=0.002), and the non-protein sulphhydryl groups content (p<0.001) were significantly increased compared to ovalbumin (group 2).MnTnHex-2-PyP restored the activities of basic enzymes in the lung antioxidant defence system in ovalbumin-induced asthma mice model, 48 hours after the last nebulization.

Our aim was to investigate the effects of MnTE-2-PyP on some markers of inflammation and lipid peroxidation in mouse asthma model. 24 female mice were divided into four groups: group 1, controls; group 2, injected with ovalbumin (OVA); group 3, treated with MnTE-2-PyP; and group 4, treated with ovalbumin and MnTE-2-PyP. The mice from groups 2 and 4 were injected with 10 μg OVA and 1 mg Imject Alum? in 100 μL phosphate buffered saline (PBS) on days 0 and 14. The animals from groups 1 and 3 were injected with 100 μL PBS + Imject Alum? (1:1). The animals from groups 2 and 4 were subjected to a 30 min aerosol challenge of 1% ovalbumin on days 24, 25 and 26 and those from groups 1 and 3 were subjected to aerosol challenge of PBS at the same time and duration. One hour before inhalation, and 12 hours later the animals from groups 3 and 4 were injected with 100 μL MnTE-2-PyP solution in PBS containing 5 mg/kg. The total cell number, total protein content and 8-isoprostane, IL-4 and IL-5 levels in the bronchialveolar lavage fluid increased in group 2 as compared to the control group. Malone dialdehyde content in the lung homogenate and IgE levels in the serum also increased in this group. The total cell number, total protein content, and levels of 8-isoprostane, IL-4, IL-5 and IgE decreased significantly in group 4 as compared to the OVA group. The parameters set out above in group 3 did not differ significantly from those of the control group. MnTE-2-PyP administered intraperitoneally, 48 hours after the last nebulization, reduced the inflammation and lipid peroxidation in mouse asthma model.

We aim ed to study the effect of a glutathione precursor, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on the lung antioxidant defense system in an animal asthma model. Materials and methods: The study was carried out on 24 female C57BL/6 mice. The mice were divided into 4 treatment groups: group 1 - control group; group 2 - injected with ovalbumin (OVA) and given an OVA inhalant; group 3 - treated with OTCA and phosphate-buffered saline inhalant; and group 4 -injected with OVA and OTCA and given an OVA inhalant. Under sodium pentobarbital anesthesia the animals were killed by exsanguination 48 h after the last inhalation to obtain a lung homogenate. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GP) and the content of nonprotein sulfhydryl (NPSH) groups in lung homogenate were investigated. Results: OVA decreased the activities of SOD (P = 0.007), CAT (P = 0.004), and GP (P = 0.05) and the NPSH content (P = 0.0008) in the lung homogenate compared with the control animals. Treatment with OVA and OTCA (group 4) resulted in a significant increase in the activities of CAT (P = 0.01) and GP (P = 0.05) and the NPSH content (P = 0.002) compared to the OVA group (group 2). Conclusion: OTCA (160 mg/kg) restored the activities of basic enzymes in the lung antioxidant defense system in an OVA-induced asthma mouse model 48 h after the last nebulization.

Background and objective: Iinvestigation of the effects of MnTnHex-2-PyP on some markers of inflammation and lipid peroxidation in an asthma mice model.Methods: The experiment was carried out on 24 female mice C57Bl/6, divided into four groups: group 1, controls; group 2, injected with ovalbumin (OVA); group 3, treated with MnTnHex-2-PyP and group 4, treated with OVA and MnTnHex-2-PyP. The animals from groups 1 and 3 were injected i.p. on days 0 and 14 with a 100 μl phosphate-buffered saline (PBS), and those from groups 2 and 4 were injected with a 100 μl ovalbumin solution, containing 20 μg OVA. On days 24, 25 and 26 the mice from groups 1 and 2 were inhaled with PBS for 30 min, and those from groups 2 and 4 were given a 1% ovalbumin solution. One hour before inhalation, and 12 hours later the animals from groups 1 and 2 were injected i.p. with 100 μl PBS, and those from groups 3 and 4 received a 100 μl MnTnHex-2-Pyp solution in PBS сontaining 0.05mg/kg.Results: Ovalbumin alone (group 2) increased the total cell number, total protein content, the levels of IL-4, IL-5 and 8-isoprostane in bronchoalveolar lavage. Elevations were observed in IgE level in serum, and the malone dialdehyde (MDA) content in the lung homogenate. These markers were decreased significantly in group 4 as compared to the OVA group.Conclusions: MnTnHex-2-Pyp reduces the inflammation and lipid peroxidation in Ovalbumin-induced mice asthma model.

EUK-134 is one of the most promising of the superoxide dismutase (SOD)/catalase mimetic compounds. The antioxidant effects of EUK-134 were tested in a rat model of paraquat pneumotoxicity.Male Wistar rats (n = 72) were divided into three groups: group 1, controls; group 2, paraquat alone; group 3, paraquat + EUK-134. Paraquat dichloride was administered per os at a dose of 80 mg/kg. EUK-134 was injected intraperitoneally at 10 mg/kg 2 h before the paraquat and again 4 h later at 5 mg/kg.On days 1, 3 and 5 after treatment with paraquat alone the LDH activity increased (P = 0.0001, P = 0.00001 and P = 0.03, respectively), and the total protein content increased (P = 0.00002, P = 0.001 and P = 0.01, respectively). The levels of acid phosphatase (AcP) in BAL fluid increased on days 1 and 3 (P = 0.006 and P = 0.04). In lung homogenates paraquat alone increased SOD activity on day 1 and decreased it on days 3 and 5. Combined treatment with paraquat and EUK-134 elevated LDH activity on day 3 (significantly less than paraquat alone) and day 5, elevated the total protein content on day 5 only, and did not change AcP activity. The combination of both agents did not alter SOD activity and decreased catalase activity on day 5 significantly less than treatment with paraquat alone (P = 0.05).EUK-134, a superoxide dismutase/catalase mimetic compound decreased the pneumotoxic effect of paraquat in rats.

Paraquat is a very toxic herbicide and a dangerous pollutant of the environment. It forms reactive oxygen species and increases the lipid peroxidation in the pulmonary cells. Our aim in this study was to estimate the protective effects of the lazaroid U-74389G possessing antilipidperoxidation activity and membrane-stabilizing effect. The experiment was carried out with 96 male Wistar rats. Paraquat dichloride was administered orally at 80mg/kg. The lazaroid U-74389G was injected intraperitoneally twice - 2h before receiving the paraquat with 10mg/kg and four hours later with 5mg/kg. Isolated application of paraquat increased enzyme activities of lactate dehydrogenase (LDH) and acid phosphatase (AcP) and the total protein content in bronchoalveolar lavage fluid (BALF). In the same experimental group the number of polymorphonuclear cells (PMNs) in BALF is elevated significantly on days 1 and 3. The combined treatment with paraquat and U-74389G did not increase the total protein content and the number of PMNs and it elevated the enzyme activities of LDH and AcP significantly less than the alone application of paraquat. It is concluded that the lazaroid U-74389G reduces the pneumotoxic effects of paraquat, estimated by sensitive cytologic and biochemical markers in BALF. The protective effect of U-74389G is well-expressed until day 3 after the treatment.

Early biochemical and histological changes in rat lungs were investigated after oral administration of 136 mg/kg 1,2-dichloroethane in oleum solution. The experiment was performed using 80 male Wistar rats. Bronchoalveolar lavage fluid and lung homogenate were examined on posttreatment days 1, 5, 15, and 30. In bronchoalveolar lavage fluid, the activities of lactate dehydrogenase, alkaline phosphatase, and acid phosphatase were elevated on day 1. The activities of superoxide dismutase, catalase, and glutathione peroxidase, and the content of malondialdehyde in lung homogenate, were also increased on day 1. The histological investigation indicated congestion, edema, and lung interstitial inflammatory changes. It was concluded that oral administration of 1,2-dichloroethane causes mild-to-moderate transitory toxic injury of the lung. Lipid peroxidation and the levels of key antioxidant enzymes are increased in the earliest posttreatment period.

BACKGROUND Airborne radioactive particles isolated from the reactor halls of nuclear power plants are a potential risk to the respiratory system of the working staff. Such radioactive dust (RD) from the Nuclear Power Plant, Kozloduy, Bulgaria was investigated. METHODS The RD was administered intratracheally to 60 male Wistar rats as an aqueous suspension and the biological effects are estimated, using sensitive biological markers in bronchoalveolar lavage fluid (BALF) and important parameters of the pulmonary antioxidant defense. RESULTS The results obtained show that RD increases the total cell number, the activities of the lactate dehydrogenase and alkaline phosphatase as well as the protein content in BALF. The activities of superoxide dismutase and catalase in lung homogenate are decreased while activity of the glutathione peroxidase and the content of non-protein sulfhydrils is elevated. CONCLUSIONS It is concluded that the RD causes transitory toxic effect on lung tissue and changes the correlation between the elements of the pulmonary antioxidative defense.

Pneumotoxic effects of the tri-n-butyl phosphate (TBP) are investigated on rats using biological markers in bronchoalveolar lavage fluid (BALF) and studying key antioxidant enzymes in lung homogenate. Each animal from the experimental group received intratracheally 5 microliters TBP (20% v/v in n-dodecane). Six rats from the control and treated groups are sacrificed on post-treatment days 1, 3, 7, 14, and 28. The lactate dehydrogenase activity, the total protein content and the total cell number in BALF are increased mainly on day 1 after the treatment. The activities of superoxide dismutase and catalase are decreased to day 7 and those of glutathione peroxidase and glutathione reductase on day 1 only. The malondialdehyde content is elevated to day 14. It is concluded that TBP causes moderate toxic injury of the lung parenchyma. The depression of the key antioxidant enzymes and the elevated lipid peroxidation are probably important mechanisms of the lung damage.

In experiments in rats it was found that 241Am transitory decreases the total cell number and alveolar macrophage's percentage in bronchoalveolar lavage fluid (BALF): increases the macrophages size and nuclear size; and increases acid phosphatase and lactate dehydrogenase activities in BALF. It was suggested that 241Am causes and activation in the alveolar macrophages which probably appears as one of factors provoking lung injuries.