Long-Term Pulmonary Histopathologic Changes in Rats Following Acute Experimental Exposure to Chlorine Gas

In this study, we aimed to investigate the long-term histopathologic changes in the lungs of rats exposed to a high concentration of chlorine gas. Twenty-four Sprague-Dawley rats were divided into three groups: the control group (group I) (n = 8), early-examined group (group II) (n = 8), and late-examined group (group III) (n = 8). In group II the lungs of rats were taken out just after the exposure, whereas in group III the lungs were taken out 45 days after the exposure. Eosinophilic liquid accumulation in alveoli and bronchi, diffuse intraalveolar edema, vascular congestion, severe perivascular edema, and free bleeding in intraalveolar and interstitial area were observed in the lungs of rats in group II. Interstitial fibrosis and thickening of the alveolar septa were observed in group III. These findings suggest that the people using these cleaning agents are at risk of harming themselves, and the victims of chlorine gas injury should be reexamined at a later period since they may have pulmonary damage even after 45 days of exposure.     

Two-week aerosol inhalation study in rats of ethylene oxide/propylene oxide copolymers.

Previous studies have shown that aerosols of an ethylene oxide/propylene oxide copolymer (UCON 50-HB-5100) produced an inflammatory response in lungs of rats in short-term repeated exposures at relatively low concentrations. This study was carried out on related polyalkylene glycols (EO/PO copolymers) to determine if similar effects would occur upon short-term repeated exposure. Rats were treated by whole body liquid droplet aerosol exposures of six hours per day, five days per week for two consecutive weeks to each of five EO/PO copolymers. The exposure level for the positive control (UCON 50-HB-5100) was 55 mg/m3, while the remaining 4 test copolymers were evaluated at 100 mg/m3. Each exposure group consisted of ten male albino rats. After three exposures, nine of ten rats exposed to UCON 50-HB-5100, and six of ten rats exposed to UCON 50-HB-2000 had died. At necropsy, congestion, consolidation and red discoloration of the lungs were noted. A moderate to severe alveolitis, characterized by intraalveolar edema, hemorrhage and fibrin deposition, was observed after five days of exposure. At necropsy, these rats exhibited elevated lung weights and similar macroscopic and microscopic lesions. Rats exposed to the other test materials (UCON 75-H-1400, Pluronic L17R1, Pluronic L31, and Pluronic L64) survived with essentially no signs of toxicity through the ten exposure days. Body weights, organ weights, hematological evaluation, pharmacotoxic signs, and macroscopic and microscopic evaluation after necropsy were similar between groups and when compared to the negative control group. Only a slight alveolitis was noted after two weeks of exposure which subsided by two-weeks post exposure.     

Two-Year Inhalation Exposure of Female and Male B6C3F1 Mice and F344 Rats to Chlorine Gas Induces Lesions Confined to the Nose

Chlorine gas is a respiratory irritant in both animals and humansthat produces concentration-dependent responses ranging fromminor irritation to death. Female and male B6C3F1 mice and F344rats were exposed to chlorine gas for up to 2 years to determinechronic toxicity and carcinogenicity. Groups of approximately70 each of female and male mice and rats were exposed to 0,0.4, 1.0, or 2.5 ppm chlorine gas for 6 hr/day, 5 days/week(mice and male rats), or 3 alternate days/week (female rats)for 2 years, with an interim necropsy of rats at 12 months (10rats/sex/concentration group). A complete necropsy was performedon all animals. Histological examination was performed on allorgans from high-concentration and control animals and selectedtarget organs from mid-and low-concentration groups. Exposure-dependentlesions were confined to the nasal passages in all sex and speciesgroups. Chlorine-induced lesions, which were most severe inthe anterior nasal cavity, included respiratory and olfactoryepithelial degeneration, septal fenestration, mucosal inflammation,respiratory epithelial hyperplasia, squamous metaplasia andgoblet cell hypertrophy and hyperplasia, and secretory metaplasiaof the transitional epithelium of the lateral meatus. Intracellularaccumulation of eosinophilic proteinaceous material was alsoa prominent response involving the respiratory, transitional,and olfactory epithelia, and in some cases the squamous epitheliumof the nasal vestibule. Many of these nasal lesions exhibitedan increase in incidence and/or severity that was related tochlorine exposure concentration and were statistically significantlyincreased at all chlorine concentrations studied. Male miceand female rats appeared more sensitive to chlorine than femalemice and male rats, respectively. The reasons for the sex differenceswithin a species were not determined. Interspecies differencesin regional dosimetry and site-specific tissue susceptibilityto chlorine exposure should be taken into account when usingthese data for accurate assessment of potential human healthrisks. The incidence of neoplasia was not increased by exposure,indicating that inhaled chlorine in rats and mice is an upperrespiratory tract toxicant but not a carcinogen.     

Behavioural change in rats due to chronic oral and systemic formaldehyde.

Impact of chronic formaldehyde exposure in respect of route on behaviour was studied. Preconditioned (environmental) male albino rats (340-400 g) in 3 groups (n = 5) under 60 days oral and systemic exposure to 10 mg/kg/day HCHO were examined for their behavioural performance (i.e. short term memory) in Cook's apparatus. Twenty percent rats settled in grade III (unconditioned avoidance response) in the i.p. (i.e. systemic group) whereas in oral fed (HCHO route in drinking water) rats, 60% settled in grade II (conditioned avoidance response) at the end of sixty days.     

Protective effects of N-acetylcysteine on peroxidative changes of the fetal rat lungs whose mothers were exposed to cigarette smoke

BACKGROUND: This experimental study investigated the protective effects of N-acetylcysteine (NAC) on peroxidative changes in fetal lungs in the offspring of rats exposed to cigarette smoke. METHODS: Thirty fetal rats used for analysis, were divided into three groups as follows: control group (n = 10), whose mothers were exposed to fresh air; group I (n =10), whose mothers were exposed to cigarette smoke; and group II (n =10), whose mothers were exposed to cigarette smoke and given 10 mg/kg per day NAC. In groups I and II, smoke exposure was started 4 weeks before the pregnancy, and continued to the 14th day of pregnancy, and in Group II, NAC was administered intraperitoneally for 14 days. The mothers and their fetuses were decapitated on the 14th day of pregnancy. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the lung tissues of fetuses to determine the oxidant-antioxidant balance. RESULTS: While tissue MDA levels in Group I were found significantly higher than the control group (129.7+/-65.4 versus 63.4 +/-15.4 nmol/100 mg protein, P <0.05), GSH levels were significantly lower (17.1+/-7.3 versus 45.4 + 8.1 nmol/mg protein, P <0.01). Furthermore, in Group II, MDA levels were significantly lower (56.9+/-20.6 versus 129.7+/-65.4 nmol/100 mg protein, P <0.05), and GSH levels were significantly higher (34.57+/-10.7 versus 17.1+/-7.3 nmol/mg protein, P <0.0001) when compared with Group I. No statistically significant difference was found in tissue MDA and GSH levels between Group II and the control group (P >0.05). CONCLUSIONS: These results suggest that smoke exposure during pregnancy causes oxidative damage in fetal lungs. This smoke-induced damage might be prevented by NAC.     

Improving the cadmium-induced centriacinar emphysema model in rats by concomitant anti-oxidant treatment

1. The aim of the present study was to perform an evolutionary analysis of the morphometrical, biochemical and functional parameters of centriacinar emphysema induced by cadmium chloride (CdCl2) in rats and to determine the effects of concomitant N-acetylcysteine (NAC) administration. 2. Male Wistar rats were instilled orotracheally with either CdCl2 (n = 24) or saline (n = 24). One group of rats, consisting of both CdCl2- and saline-treated rats, was fed a normal diet (n = 24), whereas the other group received NAC (n = 24). 3. Changes in inspiratory capacity (IC), lung compliance (CL), expiratory flow at 75% (F75), forced vital capacity (FVC) and hydroxyproline content were assessed 2, 8, 21 and 45 days after instillation. Polymorphonuclear cells were evaluated 2 and 8 days after instillation and the mean linear intercept (Lm) was determined at 21 and 45 days. 4. Over time, CdCl2 instillation causes several changes that are bound up with centriacinar emphysema. The concomitant administration of NAC to CdCl2-treated rats partially reversed Lm at 21 days compared with CdCl2 alone (115 +/- 2 vs 127 +/- 2, respectively; P < 0.05). However, 45 days after instillation, NAC improved lung function in CdCl2-treated rats compared with that in the saline-treated control group (IC 14.64 vs 15.25, respectively (P = 0.054); FVC 16.94 vs 16.28, respectively (P = 0.052), F75 31.41 vs 32.48, respectively (P = 0.062)). In addition, 45 days after instillation, NAC reduced lung collagen content in both the saline-treated control (100 vs 81% alone and in the presence of NAC, respectively) and CdCL2-treated groups (213 vs 161% alone and in the presence of NAC, respectively). In addition, although the results were not significant, NAC tended to reduce Lm and enhance CL in NAC + CdCl2-treated rats. 5. In conclusion, NAC partially improved emphysematous changes and reduced collagen deposition, which diminished the CdCl2-induced fibrotic component of centriacinar emphysema.     

Effect of iron(III) chitosan intake on the reduction of serum phosphorus in rats

Because of the widespread use of aluminium- and calcium-containing phosphate binders for the control of hyperphosphataemia in patients with end-stage renal failure, an iron(III) chitosan complex was synthesised and fed to rats to measure its effect on serum phosphorus and calcium, intestinal phosphate binding and phosphate absorption. Thirty-six Wistar rats were randomly selected and distributed into a baseline group (n = 6), a control group (n = 8 (days 0-15), n = 8 (days 16-30)) and a treatment group (n = 8 (days 0-15), n = 8 (days 16-30)). The control groups ingested AIN-76 diet mix with a 1% w/w fibre content; however, the treatment groups had the fibre content completely substituted with iron(III) chitosan. The mean weights of the treated rats were slightly lower from 15 days (not significant); but overall, rat growth was not stunted in the treatment groups. The serum phosphorus levels of the treated group (n = 8) were significantly reduced after 15 days (P = 0.004; control: 5.7+/-0.9 mg dL(-1); treatment: 4.4+/-0.5 mg dL(-1); 95% CI of difference: 0.5-2.2) and 30 days (P = 0.002; control: 5.5+/-0.9 mg dL(-1); treatment = 4.1+/-06 mg dL(-1); 95% CI of difference: 0.6-2.3) as compared with the respective control group. The serum calcium-phosphorus product was 62.0+/-12.1 mg2 dL(-2) for the control and 45.1+/-6.6 mg2 dL(-2) for the treatment group after 30 days (P = 0.004). The serum iron concentration of the treatment group did not differ from the baseline value after 15 and 30 days, but the treatment group was significantly higher than the control group (P<0.05) after 30 days. The faeces phosphorus levels (mg day(-1)) were higher (P<0.01) and its iron content was much higher (P<0.01) for the treated group. The urine phosphorus (mg kg(-1)) was not significantly reduced for the treated group, but the mean was consistently less. The kidney and liver weights of both groups were similar, but the phosphorus content of the kidney (mg (g kidney)(-1)) was higher for the treated group after 30 days (P = 0.041; control, 4.2+/-1.2 mg g(-1) vs treatment, 5.6+/-1.4 mg g(-1). Because iron(III) chitosan had a high phosphorus-binding capacity of 308 (mg P) per gram of Fe3+ for both the in-vitro (pH 7.5) and in-vivo studies, which is greater than nearly all commonly used phosphate binders, and a small net phosphorus absorption difference of 3.7 mg day(-1), it is an efficient phosphate binder for lowering serum phosphate levels without increasing serum calcium levels.     

Apparent central neurotransmitter receptor changes induced by low-level lead exposure during different developmental phases in the rat

Three groups of male Wistar rats were exposed to low concentrations of lead during different phases of their development for periods of 21 days. Exposure was initiated at conception (group I), at parturition (group II), or after weaning had occurred (group III). Mean brain lead levels achieved immediately after exposure were 1.07 +/- 0.15, 0.84 +/- 0.06, and 0.44 +/- 0.06 microgram/g in groups I, II, and III, respectively. On Day 64 postpartum radioligand binding studies were performed to determine apparent receptor densities (Bmax values) and affinities (KD values) in brain membranes of the lead-exposed rats. Lead exposure during the neonatal phase (group II) resulted in significant increases of the apparent densities of forebrain alpha 1-adrenoceptors (by 92%), cortical beta-adrenoceptors (by 116%), and striatal D-2 dopamine receptors (by 133%). Lead exposure also resulted in a significant decrease of the apparent density of striatal muscarinic receptors in group I (by 43%) and group II (by 25%) and an increase in the apparent density of hippocampal S1 receptors in group II (by 78%). Lead exposure after weaning had occurred did not alter the apparent densities of any of the receptors investigated. Receptor affinity changes, which were not identical in the three groups of rats, were also induced by lead exposure. The developmental phase during which exposure occurs appears to be a determinant of the type of neurotransmitter receptor changes induced by lead.     

Melatonin reduces urinary excretion of N-acetyl-beta-D-glucosaminidase, albumin and renal oxidative markers in diabetic rats

1. Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of the present study was to evaluate diabetic nephropathy by determining markers of oxidative stress and the urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), albumin and to investigate the possible protective effects of in vivo melatonin on renal tubular oxidative damage in diabetic rats. 2. Twenty-six rats were randomly divided into three groups: (i) group I, control, non-diabetic rats (n = 9); (ii) group II, untreated diabetic rats (n = 8); and (iii) group III, melatonin-treated diabetic rats (n = 9). In groups II and III, diabetes developed 3 days after administration of a single dose of streptozotocin (35 mg/kg, i.p.). Thereafter, whereas the rats in group II received no treatment, rats in group III began to receive 10 mg/kg per day, i.p., melatonin for 8 weeks. Malondialdehyde (MDA), an index of lipid peroxidation, NAG and microalbumin in the urine, markers of renal tubular damage, were the parameters used for oxidative stress-induced renal injury. Superoxide dismutase (SOD), xanthine oxidase (XO) and glutathione peroxidase (GSH-Px) activities were determined to evaluate changes in the anti-oxidant status of kidney tissue. 3. In untreated diabetic rats, urinary NAG, albumin and renal MDA levels were markedly increased compared with control rats (P < 0.0001). However, these parameters were reduced in diabetic rats by melatonin treatment (P < 0.0001). Urinary excretion of NAG was positively correlated with the microalbuminuria and renal MDA levels (r = 0.8; P < 0.0001). The SOD and XO activities in the untreated diabetic group were found to be significantly higher than those of the control group (P < 0.0001). Superoxide dismutase and XO activities decreased in melatonin-treated rats compared with untreated diabetic rats (P < 0.002 and P < 0.023, respectively). However, the decrease did reach levels seen in control rats. There were no significant differences in GSH-Px activity between the three groups. 4. Therefore, on the basis of these data, we suggest that urinary NAG, albumin excretion, XO activity and MDA levels are more valuable parameters showing the degree of renal tubular injury than classical markers of oxidative stress, including SOD and GSH-Px, in diabetic rat kidneys. Melatonin has an ameliorating effect on oxidative stress-induced renal tubular damage via its anti-oxidant properties. Thus, it may be suggested that urinary NAG excretion and microalbuminuria may be important markers showing the degree of renal changes and the success of long-term treatment of renal impairment with melatonin.     

Levocarnitine acetyl prevents cell death following long-term section of the vagus nerve in rats.

Levocarnitine acetyl has previously been found to significantly prevent axotomy-induced cell death in the spinal cord motor nucleus 9 and 12 months after section of the sciatic nerve in rats. In the present paper, the effects of levocarnitine acetyl on axotomy-induced cell death in the brain stem motor nuclei 90 days after section of the vagus nerve were studied. The right vagus nerve was cut at the neck. To prevent regeneration, a 5 mm-long segment of the vagus nerve was excised and the distal stump was displaced caudally. After surgery, a group of rats (n = 6) was treated with levocarnitine acetyl dissolved in the drinking water (75 mg/kg/day) (Group I). A second group of operated rats (n = 4) received drinking water alone. (Group II). Ninety days postoperatively, in the rats of both groups the proximal nerve stump of the vagus nerve was injected with horseradish peroxidase to label retrogradely the brain stem motoneurons of the dorsal motor vagal and the ambiguus nuclei. The brain stem nuclei were also labelled by horseradish peroxidase in three unoperated control rats (Group III). In the Group II rats, the number of horseradish peroxidase-labelled motoneurons of the dorsal motor vagal nucleus was found to be significantly smaller than in either the Group I (p < 0.01) or the Group III (p < 0.02) animals. In the Group I rats, the number of motoneurons of the dorsal motor vagal nucleus was not significantly smaller compared to the Group III rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined effects of niacin and chromium treatment on heart of hyperlipidemic rats

The present study was undertaken to investigate the effects of the combination of niacin and chromium(III)-chloride on heart glutathione (GSH), lipid peroxidation (LPO) levels, serum paraoxonase (PON), gamma-glutamyl transferase (GGT) activities and protein carbonyl contents (PCC) of hyperlipidemic rats. In this study, female Swiss albino rats were used. They were divided into four groups. The animals of the first group (group I) were fed with pellet chow. The rats (group II) were fed with a lipogenic diet consisting of 2% cholesterol, 0.5% cholic acid and 20% sunflower oil added to the pellet chow, and given 3% alcoholic water for 60 days. The rats (group III) were fed with the same lipogenic diet and treated by gavage technique with CrCl(3) 6H(2)O to a dose of 250 μg/kg and 100 mg/kg niacin for 45 days, 15 days after experimental animals were done hyperlipidemic. Group IV was fed with pellet chow and treated with 250 μg/kg CrCl(3) 6H(2)O and 100 mg/kg niacin for 45 days. On the 60th day, the heart tissue and blood samples were taken from animals. As a result, heart LPO, serum GGT activity and serum PCC were increased; serum PON activity and heart GSH levels were decreased in hyperlipidemic rats. Treatment with combined niacin and chromium reversed these effects. In conclusion, the combined treatment with niacin and chromium might induce a protective effect on heart tissue.     

七氟烷对大鼠缺血再灌注后肺组织氧自由基的影响

目的通过建立在体大鼠肺缺血再灌注损伤模型,观察七氟烷对缺血再灌注后肺组织氧自由基(OFRs)表达的影响,探讨缺血再灌注后肺损伤和七氟烷肺保护的可能机制。方法选择96只雄性wistar大鼠,参照改良的Eppinger方法建立在体大鼠肺缺血再灌注损伤模型。共分4组,每组24只大鼠。C组:开胸游离左肺门,未行肺门阻断;IR组:阻断肺门45min后开放再灌注;Sev-C组:吸入1MAC七氟烷30min,游离肺门不阻断;Sev-IR组:吸入七氟烷30min后阻断左肺门45min,然后开放再灌注。每组包括3个时点:缺血阻断45min、再灌注60min、再灌注120min,每时点6只大鼠,另外再灌注120min时,各组另取6只大鼠行支气管灌洗。记录各时点MAP、SpO2,测定W/D、肺通透指数(LPI),生化法检测肺组织MDA、SOD和MPO含量。结果与C组和Sev-C组比较,IR组和Sev-IR组再灌注后W/D、LPI均上升(P<0.05),Sev-IR组W/D、LPI升高的程度低于IR组(P<0.05);IR组再灌注60min、120min肺组织MDA、MPO含量增加(P<0.05),SOD含量减少(P<0.05)。Sev-IR组MDA、MPO增加、SOD减少的程度都低于IR组(P<0.05)。结论肺缺血再灌注后血管通透性增加,再灌注后肺损伤的机制与OFRs产生过多有关,七氟烷预处理能抑制OFRs的生成,对再灌注后肺组织具有一定的保护作用。     

亚慢性铝暴露对大鼠认知能力及大脑皮质β-分泌酶-1表达的影响

目的研究铝对大鼠认知能力及大脑皮质β-分泌酶-1(BACE1)蛋白表达的影响。方法健康清洁级SD大鼠32只,按体质量随机分成4组:对照组,0.27、0.54、1.08mg/kg麦芽酚铝染毒组,每组8只,采用腹腔注射方式染毒60d。采用Morris水迷宫测定大鼠学习记忆能力,采用ELISA法测定大鼠皮质BACE1蛋白表达。结果 Morris水迷宫结果显示,亚慢性铝暴露可导致大鼠游泳距离逐渐延长,而在原平台象限游泳时间则明显缩短,与对照组比较差异均具有统计学意义(P<0.05);随染毒剂量的增加,0.54、1.08mg/kg染毒组大脑皮质BACE1含量显著升高,与对照组比较差异具有统计学意义(P<0.05)。结论铝可能通过使大鼠大脑皮质BACE1表达增多而导致其认知能力受损。     

Effects of adsorption of benzo[a]pyrene onto carbon black particles on levels of DNA adducts in lungs of rats exposed by inhalation

Exposure of rodents to benzo[a]pyrene (BaP) associated with particles has previously been shown to result in increased retention of BaP and metabolites in lungs. To determine if DNA damage might be enhanced, DNA adducts were measured in lungs of F344 rats following inhalation of pure BaP aerosols or BaP absorbed on carbon black particles. Groups of rats were exposed nose only to filtered air, [14C]BaP (2 mg/m3), or [14C]BaP (2 mg/m3) adsorbed on carbon black (97 mg/m3) (BaP/CB) for 4 hr/day, 1 day/week, for 12 weeks. Groups of rats were terminated at 4, 8, 12, 16, 20, and 24 weeks after the beginning of the 12-week exposure period. Retention of total 14C in lungs was used as an indicator of total reactive metabolites. DNA isolated from lungs was analyzed for adducts using a 32P-postlabeling assay. Inhalation of BaP/CB resulted in 100-fold higher levels of 14C in lungs at the end of the 12-week exposure than did inhalation of pure BaP. The halftime for the decline in 14C levels was 34 +/- 3 weeks (mean +/- SE) for rats exposed to BaP/CB and 6 +/- 2 weeks for rats exposed to pure BaP. At the end of 12 weeks of exposure, DNA adducts in lungs of rats exposed to pure BaP ranged from 2-15 adducts per 10(9) bases (mean = 7, n = 4) and in rats exposed to pure BaP absorbed on carbon black ranged from 10-12 adducts per 10(9) bases (mean = 11, n = 4); DNA adducts in lungs of sham-exposed rats ranged from 0-2 adducts per 10(9) bases (mean = 1, n = 4). The halftimes for the decline in DNA adducts in lungs were 3 +/- 1 weeks (mean +/- SE) for the rats exposed to BaP/CB and 5 +/- 2 weeks for the rats exposed to BaP. One of the DNA adducts found following exposure to both BaP and BaP/CB was tentatively identified as the BaP diol epoxide deoxyguanosine (BPDE) adduct. Levels of both total and BPDE DNA adducts were significantly increased (p less than 0.05) in lungs of rats exposed to both BaP and BaP/CB compared to levels in lungs of sham-exposed rats. There were no significant differences in levels of DNA adducts in lungs of rats exposed to BaP or BaP/CB, although the pattern of adducts was different between the two exposure modes.(ABSTRACT TRUNCATED AT 400 WORDS)     

Oxidative DNA damage and total antioxidant status in rats during experimental gram-negative sepsis

Sepsis and septic shock remains as leading cause of death in adult intensive care units. It is widely accepted that gram-negative bacteria and their endotoxins cause sepsis and septic shock, predominantly. Enhanced generation of reactive oxygen species may be responsible for tissue injury in septic shock and endotoxemia. The aim of this study was to assess oxidative DNA damage and the total antioxidant status (TAS) in peripheral lymphocytes of rats during different intraperitoneal gram-negative sepsis stages. Adult male Sprague-Dawley rats were divided randomly into four groups. Control group was intraperitoneally inoculated with 2 mL of pyrogene-free saline (Group I, n = 6), and the other rats received an intraperitoneal inoculum with 2 mL of saline containing 2 x 10(8) CFU of Escherichia coli. The animals were killed at time zero (Group I, n = 6), at 6th (Group II, n = 7), 12th (Group III, n = 7), and 24th (Group IV, n = 7) hour after the E. coli inoculation. Oxidative DNA damage in peripheral lymphocytes of rats was evaluated by modified comet assay (single-cell gel electrophoresis). Formamidopyrimidine DNA glycosylase (Fpg) and Endonuclease III (Endo III) were used to detect oxidized purines and pyrimidines, respectively. Total antioxidant quantification was carried out using ABTS+ (2,2'-Azino-di-[3 ethylbenzthiazoline sulphonate]) radical formation kinetics (Randox kit) in serum samples. Significant elevations of basal levels of strand breaks (SB) in Group IV were observed as compared with Group I, II, and III. There was a significant increase in Fpg sites in Group III as compared with Group I and II. However, there was no significant difference in terms of Endo III sites in any of the groups. Although the TAS was decreased with the stages of sepsis, this moderate decrease was significant in only Group IV as compared with Group I. There was no statistically significant correlation between DNA damage and TAS for any of the groups.     

The fate of antioxidant enzymes in bronchoalveolar lavage fluid over 7 days in mice with acute lung injury

Characterization of lung injury is important if timely therapeutic intervention is to be used properly and successfully. In this study, lung injury was defined as the progressive formation of pulmonary edema. Our model gas was phosgene, a pulmonary edemagenic compound. Phosgene, widely used in industry, can produce life-threatening pulmonary edema within hours of exposure. Four groups of 40 CD-1 male mice were exposed whole-body to either air or a concentration x time (c x t) amount of 32-42 mg/m(3) (8-11 ppm) phosgene for 20 min (640-840 mg x min/m(3)). Groups of air- or phosgene-exposed mice were euthanized 1, 4, 8, 12, 24, 48, or 72 h or 7 days postexposure. The trachea was excised, and 800 micro l saline was instilled into the lungs and washed back and forth 5 times to collect bronchoalveolar lavage fluid (BALF). The antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), total glutathione (GSH), and protein were determined at each time point. Phosgene exposure significantly enhanced both GPx and GR in phosgene-exposed mice compared with air-exposed mice from 4 to 72 h, p < or = 0.01 and p < or = 0.005, respectively. BALF GSH was also significantly increased, p < or = 0.01, from 4 to 24 h after exposure, in comparison with air-exposed. BALF protein, an indicator of air/blood barrier integrity, was significantly higher than in air-exposed mice 4 h to 7 days after exposure. In contrast, BALF SOD was reduced by phosgene exposure from 4 to 24 h, p < or = 0.01, versus air-exposed mice. Except for protein, all parameters returned to control levels by 7 days postexposure. These data indicate that the lung has the capacity to repair itself within 24-48 h after exposure by reestablishing a functional GSH redox system despite increased protein leakage. SOD reduction during increased leakage may indicate that barrier integrity is affected by superoxide anion production.     

Pulmonary changes resulting from subchronic exposure to cadmium chloride aerosol

Fischer-344 rats were exposed to 0.0, 0.3, 1.0, or 2.0 mg Cd/m3 as CdCl2 aerosol for 6 h/d, 5 d/wk, for 62 exposure days. Exposure to 2.0 mg Cd/m3 resulted in rapid weight loss, and all of the animals died within the first 45 exposure days. As a group, female rats survived significantly longer than the males. Exposure to Cd resulted in dose-dependent increases in lung weight. The increased weight was the result of additional tissue mass rather than edema. Both connective-tissue components, elastin and collagen, were significantly increased in the 1.0-mg/m3 group when these components were expressed on the basis of dry weight. Dose-dependent changes at the terminal bronchioles consisted of hyperplasia and flattening of type II cells, inflammation, and the proliferation of fibroblasts. Exposure to Cd also resulted in the development of intralymphatic microgranulomas in the perivascular and peribronchiolar lymphoid tissues.     

Pharmacological studies on experimental nephritic rats (13). The development and aggravation of nephritis due to the repeated administration of liquoid (author's transl)

In order to elucidate the role of blood coagulation system in the development and aggravation of glomerulonephritis, liquoid (Liq) was repeatedly administered to normal or nephritic rats. When Liq 10 mg/kg was given i.v. daily X 22 to normal rats (group I), the urinary excretions of protein and N-acetyl-beta-glucosaminidase and urea nitrogen content did not significantly change as compared with those in the normal control group. In rats given Liq 10 mg/kg i.v. either every 3 days X 8 (group III) or every day X 22 (group IV) from the 15th day after the i.v. administration of anti-rat glomerular basement membrane rabbit serum (AGS) [0.5 ml/150g body weight], these biochemical parameters were not significantly different from those of nephritic control rats given AGS only (group II). The deposits of fibrin or fibrinoids in glomeruli of groups I, II, III and IV, examined by a fluorescence antibody technique were evident in 2, 2, 8 and 10, respectively, out of 10 rats in each group, although the degree of deposition was slight. Under light microscopy, the adhesion between the glomerular capillary wall and Bowman's capsule, hypercellularity, crescent formation and hyalinization were demonstrated in a part of glomeruli, even in group I. concerning the influence of Liq in nephritic rats, the most prominent glomerular change was hyalinization. While in group II the hyalinization was evident in only 17% of glomeruli, in groups III and IV the hyalinization was 41 and 55%, respectively. Although no significant difference was seen between groups II and III regarding other glomerular changes except for hypercellularity, these changes in group IV increased as compared with those in group II. However, hypercellularity was less in groups III and IV than in group II. A slight occlusion of the glomerular capillary lumen was observed, even in group I. In nephritic groups, the degree of the capillary lumen occlusion in group IV was greater than that in group II. From these results, the acceleration of intraglomerular blood coagulation is considered to be a major factor in the development and aggravation of glomerulonephritis.     

The effects of exercise following exposure to bis(trifluoromethyl) disulfide.

Bis(trifluoromethyl) disulfide (TFD) was originally designed for use as an agricultural fumigant. Inhalation of toxic doses of TFD results in varying degrees of pulmonary edema. The purpose of this study was to determine if exhaustive exercise would potentiate the toxic effects of TFD. One group of treadmill-acclimated rats was exercised to exhaustion following a 10-minute whole-body exposure to TFD. A second group was similarly exposed but not exercised. Two other groups of rats were sham exposed; one was exercised while one remained sedentary following the sham exposure. Twenty-four hours after exposure, the animals were sacrificed; the lungs were removed and weighed, and a portion was collected for histopathologic examination. The remaining lung tissue was allowed to dry to constant weight. There was no difference in endurance times between exposed and sham-exposed rats. There was a significant increase in the amount of pulmonary edema and associated pulmonary pathology in rats exercised following exposure to TFD. Eleven of twelve animals exercised following exposure to TFD and three of twelve animals which remained sedentary following exposure died by 24 hours. The degree of pulmonary pathology in all rats exposed to TFD was profound.