Alterations In Liver Tissues Research Articles

Anti-inflammatory Montelukast prevents toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin

This study aimed to investigate the potential beneficial effects of the montelukast (ML) on oxidative stress and histological alterations in liver tissues and cytokine levels in rats intoxicated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were divided randomly into four equal groups (control, TCDD, ML, TCDD + ML). TCDD were administered by gavages dissolved in corn oil at the doses of 2 µg/kg/week, and ML was given intraperitoneally at the dose of 10 mg/kg/day. Oxidative status, histological alterations, and cytokine levels were analyzed on day 60. The results showed that although TCDD induced oxidative stress via significant increase in formation of thiobarbituric acid reactive substance, it caused a significant decline in glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in liver. Besides, TCDD led to significant histopathological damage in liver and serum cytokine levels alterations (increase in tumor necrosis factor α and interleukin 1β levels). In contrast, ML treatment reversed oxidative effects of TCDD by increasing the levels of GSH, CAT, and SOD and decreasing the formation of TBARS. Also, it can normalize the levels of histological and cytokine alterations induced by TCDD. In conclusion, it was determined that TCDD exposure caused adverse effects on cytokine levels, histological alterations, and oxidative stress in rats. However, ML treatment partially eliminated toxic effects of TCDD. Thus, it was judged that coadministration of ML with TCDD may be useful to attenuate the negative effects of TCDD.

FT-Raman study of deferoxamine and deferiprone exhibits potent amelioration of structural changes in the liver tissues of mice due to aluminum exposure

The present study inform the alterations on major biochemical constituents such as lipids, proteins, nucleic acids and glycogen along with phosphodiester linkages, tryptophan bands, tyrosine doublet, disulfide bridge conformations, aliphatic hydrophobic residue, and salt bridges in liver tissues of mice using Fourier transform Raman spectroscopy. In amide I, amide II and amide III, the area value significant decrease due structural alteration in the protein, glycogen and triglycerides levels but chelating agents DFP and DFO upturned it. Morphology changes by aluminium induced alterations and recovery by chelating agents within liver tissues known by histopathological examination. Concentrations of trace elements were found by ICP-OES. FT-Raman study was revealed to be in agreement with biochemical studies and demonstrate that it can successfully specify the molecular alteration in liver tissues. The tyrosyl doublet ratio I899/I831 decreases more in aluminum intoxicated tissues but treatment with DFP and DFO+DFP brings back to nearer control value. This indicates more variation in the hydrogen bonding of the phenolic hydroxyl group due to aluminum poisoning. The decreased Raman intensity ratio (I3220/I3400) observed in the aluminum induced tissues suggests a decreased water domain size, which could be interpreted in terms of weaker hydrogen-bonded molecular species of water in the aluminum intoxicated liver tissues. Finally, FT-Raman spectroscopy might be a useful tool for obtained successfully to indicate the molecular level changes.

Saturated Hydrogen Saline Attenuates Endotoxin-Induced Acute Liver Dysfunction in Rats

To determine the effect of saturated hydrogen saline on lipopolysaccharide (LPS)-induced acute liver dysfunction, rats were divided into control, LPS, and LPS plus saturated hydrogen saline (LPS+H(2)) groups. Treatment with saturated hydrogen saline prolonged the median survival time and reduced liver dysfunction. Moreover, saturated hydrogen saline significantly reduced pathological alterations in liver tissues, the number of ballooned hepatocytes, serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels, and myeloperoxidase (MPO) and malondialdehyde (MDA) levels in liver tissues (P<0.05). Cell apoptosis was detected in liver tissues after LPS treatment, and attenuated by saturated hydrogen saline treatment. Saturated hydrogen saline also decreased phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated Jun kinase (p-JNK), nuclear factor-kappa B (NF-kappaB), and second mitochondria-derived activator of caspase (Smac) levels, and increased p38 activation (P<0.05). Thus, saturated hydrogen saline may attenuate LPS-induced acute liver dysfunction in rats, possibly by reducing inflammation and cell apoptosis. Mitogen-activated protein kinase (MAPK), NF-kappaB, and Smac may contribute to saturated hydrogen saline-mediated liver protection.

Determination of aluminium induced metabolic changes in mice liver: A Fourier transform infrared spectroscopy study

In this study, we made a new approach to evaluate aluminium induced metabolic changes in liver tissue of mice using Fourier transform infrared spectroscopy analysis taking one step further in correlation with strong biochemical evidence. This finding reveals the alterations on the major biochemical constituents, such as lipids, proteins, nucleic acids and glycogen of the liver tissues of mice. The peak area value of amide A significantly decrease from 288.278±3.121 to 189.872±2.012 between control and aluminium treated liver tissue respectively. Amide I and amide II peak area value also decrease from 40.749±2.052 to 21.170±1.311 and 13.167±1.441 to 8.953±0.548 in aluminium treated liver tissue respectively. This result suggests an alteration in the protein profile. The absence of olefinicCH stretching band and CO stretching of triglycerides in aluminium treated liver suggests an altered lipid levels due to aluminium exposure. Significant shift in the peak position of glycogen may be the interruption of aluminium in the calcium metabolism and the reduced level of calcium. The overall findings exhibit that the liver metabolic program is altered through increasing the structural modification in proteins, triglycerides and quantitative alteration in proteins, lipids, and glycogen. All the above mentioned modifications were protected in desferrioxamine treated mice. Histopathological results also revealed impairment of aluminium induced alterations in liver tissue. The results of the FTIR study were found to be in agreement with biochemical studies and which demonstrate FTIR can be used successfully to indicate the molecular level changes.

A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging

Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD.

Toxicogenomic-based approaches predicting liver toxicity in vitro

Toxicogenomic-based approaches represent a powerful tool for the identification of toxic pathways in vivo (Ellinger-Ziegelbauer et al. 2008; Fielden et al. 2007) and for gene signatures that predict carcinogenic events and tumor development (Schmidt et al. 2008; 2012; Cadenas et al. 2010; Petry et al. 2010). The most successful studies in the field of Toxicology have thus far relied on in vivo exposure of laboratory animals. These studies have correctly predicted the carcinogenicity of compounds and whether they can be categorized as genotoxic or nongenotoxic carcinogens from gene expression alterations in liver tissue (Fielden et al. 2011; Ellinger-Ziegelbauer et al. 2008). However, until today, systematic classification studies have only been performed in vivo. Cultivated hepatocytes have always been a well-accepted tool to study drug metabolism enzyme induction, cytotoxicity and signal transduction (Hewitt et al. 2007; Vinken et al. 2011; Bolt and Stewart 2010; Knobeloch et al. 2012; Meyer et al. 2011; Ilowski et al. 2010; 2011; Hoehme et al. 2010; Watanabe et al. 2011; Nakagawa et al. 2011; Drobna et al. 2010). However, their use in toxicogenomics is still problematic (Godoy et al. 2010a, b; Schug et al. 2008). When hepatocytes are isolated from the liver and brought into culture, they have a propensity to dedifferentiate displaying features of epithelial to mesenchymal transition (Godoy et al. 2009, 2010a, b). This process also takes place in three-dimensional cell systems, such as the sandwich culture. This is especially apparent during the first 24 h in culture when a large number of genes are upor downregulated as a consequence of cell isolation and culture conditions (Zellmer et al. 2010). Therefore, it should be critically evaluated whether test compound-induced gene expression alterations under conditions of an ‘‘unstable background’’ can be identified. Previous studies were rather discouraging. For example, Kienhuis et al. (2009) reported that there is almost no overlap between gene expression alterations induced by paracetamol in the livers of rats compared to cultivated hepatocytes. To systematically address the possible in vitro/in vivo discrepancy, Heise and colleagues (Heise et al. 2012) compared gene expression alterations induced by carcinogens in rat livers and in cultivated hepatocytes. They observed that expression alterations in genes associated with stress response, metabolism and DNA repair showed a significant in vivo/in vitro correlation (Heise et al. 2012). In contrast, genes associated with proliferation did not lead to similar results in vivo and in vitro. One explanation may be that the in vitro hepatocyte system, in contrast to the in vivo liver, could not undergo replacement proliferation after killing of hepatocytes by the test compounds. Overall, the results (Heise et al. 2012) demonstrate the importance of studying the in vitro functions that are maintained and those that no longer work in an in vivo-like manner. In the future, it will be interesting to learn whether the genes that still show in vivo-like responses in culture offer a sufficient basis for toxicogenomic approaches in vitro.

Inhibition of experimental HCC growth in mice by use of the kinase inhibitor DMAT

The multi-kinase-inhibitor Sorafenib has been shown to prolong survival of patients suffering from hepatocellular carcinoma (HCC). We investigated effects of the serine/threonine kinase inhibitor 2-Dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) on experimental HCC growth, and identified mechanisms and target kinases of DMAT. Our results show that DMAT application in vivo reduced tumor growth in a xenotransplant model by interference with tumor cell proliferation. Biochemical parameters and histology following DMAT administration revealed no alterations in liver tissue. Similar to Sorafenib, DMAT interfered with NFκB activation and Wnt-signaling. Of the kinases inhibited by DMAT at almost equimolar IC50, CK2 and PIM-3 were found to be over-expressed or more active in hepatoma cells and human HCC tissue. Knockdown of PIM-3 or CK2 by shRNA revealed that both kinases are important for hepatoma cell proliferation and survival. In conclusion, DMAT reduces HCC growth by interference with NFκB- and Wnt-signaling. PIM-3 and CK2 seem to be important target kinases. Inhibition of these kinases by application of inhibitors, e.g., DMAT, might represent a promising therapeutic approach in future HCC therapy.

Cisplatin Induced Histological and Ultrastructural Alterations In Liver Tissue of Rat

Background: Cisplatin is well-known anticancer drug often been used for treatment of various human malignancies. The hepatotoxic or nephrotoxic effect of drug is a result of altered histological and antioxidant status of the organ. In order to document the extent of cisplatin (CDDP) effect on liver we have studied long term treatment of cisplatin (CDDP) to rat. In our previous studies we have demonstrated changes in reduced glutathione (GSH) and glutathione related enzymes of liver followed by increased lipid peroxidation process. Materials: Light microscopy (LM) was carried out in liver tissue by haematoxylin and eosin staining. Electron microscopy was performed by staining with uranil acetate and lead citrate. Results: Recent reports depicts that CDDP treatment caused significant alteration at histopathological level showing increased vacuolation in hepatocytes. A noticeable change observed after drug treatment is large perilobular connective and expanded portal spaces. Morphological alterations after transmission electron microscopy (TEM) showed heterochromatic border in nucleus followed by prescence of large agglutinations of lysosomes, numerous rough endoplasmic reticulum (RER) and mitochondria has been observed as one of the significant effect of drug. Conclusion: Thus cytoarchitectural studies signify that long term of CDDP intervention at 0.4 mg/kg/day/animal caused least damage to liver.

Hepatic Changes During Various Periods of Reperfusion After Induction of Renal Ischemia in Rats

Recent studies have suggested that ischemic damage to the kidneys causes liver tissue alterations. Thus, the morbidity and mortality in patients with acute renal failure (ARF) may be related to liver complications as well as to renal injury. The aim of the present study was to assess the hepatic changes during various periods of reperfusion after induction of renal ischemia. Forty male rats were subjected to either a sham operation or to a 45-minute ischemia followed by 1, 3, 6, or 24 hours of reperfusion. Arterial pressure was continuously monitored. Blood samples were drawn to measure serum creatinine and blood urea nitrogen (BUN). We evaluated hepatic concentrations of interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha. Ischemia reperfusion (IR) caused significant reductions in renal function as demonstrated by increased values of serum creatinine and BUN. These rats also showed significant increases in hepatic TNF-alpha and IL-10 concentrations. The most significant changes among inflammatory factors in the liver were observed at 3 hours of reperfusion: TNF-alpha, 616 +/- 41 vs 215 +/- 16, and IL-10, 926 +/- 73 vs 125 +/- 34, pg/100 mg tissue (P <or= .05). Twenty-four-hour reperfusion reduced the extent of liver injury. Renal IR affects liver inflammatory status, possibly due to increased renal production or impaired clearance of mediators of tissue injury, namely proinflammatory cytokines. The reduction in liver injury at 24 hours of reperfusion compared with the other groups, suggested activation of late-protective mechanisms. These observations may be important for clinical interventions to reduce the morbidity and mortality of ARF.

Investigation of liver tissue and biochemical parameters of adult wistar rats treated with Arctium lappa L.

This study was carried out to evaluate the effects of Arctium lappa L. (burdock) on the liver of adult male Wistar rats as measured by light microscopy and biochemical parameters. The rats received the extract in water bottles at doses of 10 or 20 g/L daily for 40 days. There were no significant changes in the plasma levels of albumin, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT), total protein, total cholesterol, urea, uric acid, triacylglycerol, calcium, phosphorus, chlorine and direct bilirubin. The morphological analysis did not reveal histopathological alterations in liver tissue. Both biochemical and morphological data did not indicate A. lappa toxicity.

Acute viral hepatitis increases liver stiffness values measured by transient elastography

Liver tissue alterations other than fibrosis may have an impact on liver stiffness measurement. In this study we evaluated 18 patients without a previous clinical history of liver disease, consecutively admitted for acute viral hepatitis. In each patient, aminotransferase determination and liver stiffness measurement were performed on the same study day, at 3 different points: (1) peak increase in aminotransferase; (2) aminotransferase 50% or less of the peak; (3) aminotransferase levels <or=2x the upper limit of normal. In all patients, the degree of liver stiffness at the time of the peak increase in aminotransferases exceeded the cutoff values proposed for the prediction of significant fibrosis or cirrhosis. A progressive significant reduction in liver stiffness values was observed (P < 0.0001) in the follow-up period in parallel with the reduction of aminotransferase levels (P < 0.0001). Moreover, a statistically significant, positive correlation between aminotransferases and liver stiffness measurement (LSM) at the onset of acute viral hepatitis was found (r = 0.53, P = 0.02 and r = 0.51, P = 0.03 for alanine aminotransferase and aspartate aminotransferase, respectively). In conclusion, the extent of necroinflammatory activity needs to be carefully considered in future studies aimed at further validating transient elastography, particularly in patients with absent or low-stage liver fibrosis (in other words, F0-F2 METAVIR). LSM does not represent a reliable instrument to detect the presence of advanced fibrosis and cirrhosis in patients presenting with a clinical picture of acute hepatitis.

Multigenerational study of the hepatic effects exerted by the consumption of nonylphenol- and 4-octylphenol-contaminated drinking water in Sprague–Dawley rats

Our multigenerational study evaluates the hepatic effects of the xenoestrogens nonylphenol (NP), and 4-octylphenol (4OP) on male and female rats when they are exposed uninterruptedly, from conception to adult age, to tap water containing 25 ppm of NP or 4OP. Our results showed that these compounds did not induce any change in liver/body weight ratio (relative liver weight, RLW). In the morphological analysis we did not find evident signs of cytotoxicity. The most relevant findings were the presence of both an increase in the apoptotic index and in the percentage of binuclear hepatocytes in livers from exposed animals. Additionally, our study revealed the presence of hepatocellular glycogenosis (mainly in 4OP-exposed rats): the type of glycogen accumulated was in aggregates (gamma-glycogen), a non-functional form of glycogen. This study demonstrates that, at levels close to those described in the environment, NP and 4OP are capable of inducing a number of hepatic effects, potentially related with adaptive, and/or metabolic alterations of liver tissue.

Selenium Treatment Protects Diabetes-Induced Biochemical and Ultrastructural Alterations in Liver Tissue

We have shown that a single dose of streptozotocin (STZ) (50 mg/kg body weight) injected into rats caused significant changes in some antioxidant enzyme activities, such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities, and acid-soluble sulfhydryl levels of the liver tissue with respect to the control rats. Furthermore, these alterations in the activities of the antioxidant enzymes were accompanied by significant changes in the ultrastructure of the liver tissue; mainly intercellular biliary canaliculi were distended and contained stagnant bile, swollen mitochondria in hepatocytes and disoriented and disintegrating cristae, dilatation of the rough endoplasmic reticulum (rER) with detachment of ribosomes, and dissociation of polysomes. Both diabetic and normal rats were treated with sodium selenite (5 micromol/kg/d, intra peritoneally) for 4 wk following 1 wk of diabetes induction. This treatment of diabetic rats improved significantly diabetes-induced alterations in liver antioxidant enzymes. Moreover, treating of diabetic rats with sodium selenite prevented primarily the variation in staining quality of hepatocytes nuclei, increased density and eosinophilia of the cytoplasm, focal sinusoidal dilatation and congestion, and increased numbers of mitochondria with different size and shape. In summary, treatment of diabetic rats with sodium selenite has beneficial effects on both antioxidant system and the ultrastructure of the liver tissue. These findings suggest that diabetes-induced oxidative stress can be responsible for the development of diabetic complications and antioxidant treatment can protect the target organs against diabetes.

Morphological alterations in liver tissues from rabbits exposed to crude oil contaminated diets.

Morphological alterations in liver tissues from rabbits exposed to crude oil contaminated diets.

Current status and prospects of studies on human genetic alleles associated with hepatitis B virus infection.

Chronic hepatitis B virus (HBV) infection can cause a broad spectrum diseases, including from asymptomatic HBV carriers or cryptic hepatitis, to acute hepatitis, chronic hepatitis, Liver cirrhosis and primary hepatocellular carcinoma. The variable pattern and clinical outcome of the infection were mainly determined by virological itself factors, host immunological factors and genetic factors as well as the experimental factors. Among the human genetic factors, major candidate or identified genes involved in the process of HBV infection fall into the following categories: (1) genes that mediate the processes of viral entry into hepatocytes, including genes involved in viral binding, fusion with cellular membrane and transportation in target cells; (2) genes that modulate or control the immune response to HBV infection; (3) genes that participate in the pathological alterations in liver tissue; (4) genes involved in the development of liver cirrhosis and hepatocellular carcinoma associated with chronic HBV infection, including genes related to mother-to-infant transmission of HBV infection; and (5) those that contribute to resistance to antiviral therapies. Most of the reports of human genes associated with HBV infection have currently focused on HLA associations. For example, some investigators reported the association of the HLA class II alleles such as DRB1*1302 or HLA-DR13 or DQA1*0501-DQB1*0301-DQB1*1102 haplotypes with acute and/or chronic hepatitis B virus infection, respectively. Several pro-inflammatory cytokines such as Th1 cytokines (including IL-2 and IFN-gamma) and TNF-alpha have been identified to participate the process of viral clearance and host immune response to HBV. In contrast, the Th2 cytokine IL-10 serves as a potent inhibitor of Th1 effector cells in HBV diseases. The MBP polymorphisms in its encoding region were found to be involved in chronic infection. Thus, reports from various laboratories have shown some inconsistencies with regard to the effects of host genetic factors on HBV clearance and persistence. Since genetic interactions are complex, it is unlikely that a single allelic variant is responsible for HBV resistance or susceptibility. However, the collective influence of several single nucleotide polymorphisms (SNPs) or haplotype (s) may underlie the natural combinational or synergistic protection against HBV. The future study including the multi-cohort collaboration will be needed to clarify these preliminary associations and identify other potential candidate genes. The ongoing study of the distributions and functions of the implicated allele polymorphisms will not only provide insight into the pathogenesis of HBV infection, but may also provide a novel rationale for new methods of diagnosis and therapeutic strategies.

Evaluating the genotoxic damage and hepatic tissue alterations in demersal fish species: a case study in the Ligurian Sea (NW-Mediterranean)

A protocol for detecting hepatic micronuclei in fish was performed to check genotoxic damage, as an indicator of environmental hydrocarbons exposure, in relation to the “ Haven” oil spill. As target fish, we have chosen three demersal species with different habitats and feeding behaviour (i.e., Lepidorhombus boscii, Merluccius merluccius and Mullus barbatus) collected from two differently impacted areas and a control site. Additional analysis was performed by histological detection of hepatic tissue damages such as the presence of necrotic and tumour-like aspects. The three studied species showed different sensitivity to environmental pollutants exposure, L. boscii resulting the more sensitive in terms of both micronuclei incidence and tissue damage. The results of this study show that: (1) the micronucleus test could be an effective and fast method to detect oil pollution; (2) a clear response of L. boscii only to oil contamination for both micronucleus test and liver tissue alterations.

EFFECT OF BILE DUCT OBSTRUCTION ON HEPATIC UPTAKE OF 1-METHYL-4-PHENYLPYRIDINIUM IN THE RAT

Previous studies have demonstrated that the organic cation 1-methyl-4-phenylpyridinium (MPP+) is avidly taken up by rat freshly isolated hepatocytes through at least two distinct transport mechanisms: the type I hepatic transporter of organic cations and P-glycoprotein. In this study, the effects of extrahepatic cholestasis induced by bile duct ligation for 4 days on the uptake of [3H]MPP+by rat freshly isolated hepatocytes and liver slices were determined. Bile duct ligation produced no significant alterations in the characteristics of [3H]MPP+uptake by freshly isolated hepatocytes. The strong correlation found between the effect of various drugs on [3H]MPP+uptake by hepatocytes from control and treated rats (r=0.958;P<0.0001;n=15) suggests that neither the type I hepatic transporter of organic cations nor P-glycoprotein were affected by bile duct ligation. On the contrary, uptake of [3H]MPP+by liver slices was markedly changed after bile duct ligation: (1) there was a significant increase (≅40%) in the amount of [3H]MPP+taken up by liver slices from bile duct-ligated rats; (2) there was no correlation between the effect of various drugs on [3H]MPP+uptake by liver slices from control and treated rats (r=0.772;P=0.072;n=6). On the basis of (1) the lack of effect of bile duct ligation on [3H]MPP+uptake by isolated hepatocytes; and (2) the profound morphological alterations of liver tissue observed 4 days after bile duct ligation (increase in volume density of bile ductules, ductular cells and infiltration of inflammatory cells), we suggest that non-parenchymal liver cells have an important participation in the hepatic uptake of [3H]MPP+after bile duct ligation in the rat.

Chemical and Biological Investigations of a Transformer Accident at Binghamton, NY

A transformer fire occurred in a state office building in Binghamton, NY on February 5, 1981. Particulates from inside surfaces of ceiling panels on 16 of the 17 floors had concentrations of polychlorinated dibenzofurans (PCDFs) ranging from &lt; 1 part per million (ppm) to 1200 ppm while polychlorinated biphenyl (PCB) concentrations varied from 28 ppm to 23,000 ppm. In spite of the wide variations in contaminant concentrations, complete analytical data from 11 floors showed that there was a consistent PCDF/PCB ratio (0.067 ± 0.026) and also consistent PCDF isomer group distributions (tetra-CDFs, 33 ± 5%; penta-CDFs, 40 ± 3%; hexa-CDFs, 18 ± 7%; hepta-CDFs, 6 ± 3%). It was found that the particulate samples could be successfully ranked in order of their degree of chemical contamination by an in vitro bioassay. The bioassay was based on induction of keratinization or changes in morphology in mouse epithelial cells. Animal toxicology experiments were carried out with a soot sample containing a PCDF concentration which approximated the mean value found on the ceiling particulates. The single dose oral LD values of the soot and its benzene extract equivalent, each administered to female guinea pigs in 0.75% methyl cellulose, were 410 and 327 mg/kg, respectively. These results demonstrated that the soot matrix had virtually no effect on the toxicity of the chemical contaminants in the soot. Morphological alterations in liver tissues from animals receiving the soot were found after examination by electron and light microscopy. Rabbits dermally exposed to the soot and its benzene extract at 500 mg/kg showed evidence of hypertrophy of centrilobular hepatocytes. In addition the rabbits exposed to the soot extract had a local inflammatory reaction at the site of application. In a subchronic feeding experiment carried out for 90 days with guinea pigs, the lowest effect level was found with an accumulated dose of 1.2 mg soot/kg. The observed effects included salivary gland duct metaplasia and decreased relative thymus weights. Based on the chemical analysis data and literature LD values for the more toxic 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and PCDFs, it was calculated that the soot contained the equivalent of 44 ppm 2,3,7,8-tetra-CDD in terms of toxicity to guinea pigs. This was in close agreement with the value of 58 ppm derived from the acute oral toxicity experiments. Air sampling, accomplished on 8 floors in the final stages of the building cleanup, showed maximum total PCDF and 2,3,7,8-tetra-CDF concentrations of 264 and 23 pg/m, respectively.

Chemical and biological investigations of a transformer accident at Binghamton, NY

A transformer fire occurred in a state office building in Binghamton, NY on February 5, 1981. Particulates from inside surfaces of ceiling panels on 16 of the 17 floors had concentrations of polychlorinated dibenzofurans (PCDFs) ranging from less than 1 part per million (ppm) to 1200 ppm while polychlorinated biphenyl (PCB) concentrations varied from 28 ppm to 23,000 ppm. In spite of the wide variations in contaminant concentrations, complete analytical data from 11 floors showed that there was a consistent PCDF/PCB ratio (0.067 +/- 0.026) and also consistent PCDF isomer group distributions (tetra-CDFs, 33 +/- 5%; penta-CDFs, 40 +/- 3%; hexa-CDFs, 18 +/- 7%; hepta-CDFs, 6 +/- 3%). It was found that the particulate samples could be successfully ranked in order of their degree of chemical contamination by an in vitro bioassay. The bioassay was based on induction of keratinization or changes in morphology in mouse epithelial cells. Animal toxicology experiments were carried out with a soot sample containing a PCDF concentration which approximated the mean value found on the ceiling particulates. The single dose oral LD values of the soot and its benzene extract equivalent, each administered to female guinea pigs in 0.75% methyl cellulose, were 410 and 327 mg/kg, respectively. These results demonstrated that the soot matrix had virtually no effect on the toxicity of the chemical contaminants in the soot. Morphological alterations in liver tissues from animals receiving the soot were found after examination by electron and light microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of voluntary exercise and dietary protein levels on the activity of serum glutamic pyruvic transaminase and the morphological picture of liver in mice.

In the present investigation, effects of voluntary exercise on serum glutamic pyruvic transaminase (SGPT) activity and histological alterations of liver tissue of mice fed 4%, 6% and 20% casein diet were examined. AGPT activity showed decreasing values accompanied by dietary protein level increases. In 4% casein diet groups, SGPT activity of the exercise group was markedly lower than that of the non-exercise group. Furthermore, there was a negative correlation between SGPT and LCAT activity. In histological evaluation, the non-exercise group on 4% casein diet revealed diffuse fatty degeneration of the liver, but the exercise group did not show such changes.