Irgarol inhibits the synthesis of ATP in mitochondria from rat liver

The interactions of Irgarol with rat liver mithocondrial have been investigated. The results indicate that Irgarol inhibits the ATP synthesis. The analysis of the various steps involved in the ATP synthesis suggests that the inhibition is due to the opening of small-size pores.     

Effects of the aflatoxins on ATPase activities in mouse and rat liver.

The effects of the aflatoxins on ATPase activities in mouse and rat tissues were investigated in vitro. The hepatic oligomycin-sensitive (O.S.) Mg++ ATPase was inhibited significantly. The order of inhibition was G1 greater than B1 greater than G2 greater than B2. Mouse O.S. Mg++ ATPase was more sensitive than the corresponding rat enzyme. The oligomycin-insensitive (O.I.) Mg++ ATPase activities in rat and mouse liver were not altered. Although aflatoxins G1 and B1 were more potent inhibitors of hepatic O.S. Mg++ ATPase, no concentration-response was observed, whereas aflatoxins G2 and B2 inhibited enzyme activity in a concentration-dependent manner. Spectral analysis of aflatoxin G1 solutions suggested that solubility was not related to the observed effects. In addition, the effects of aflatoxin B1 and G1 on mouse brain microsomal Na+-K+ ATPase were examined. Although aflatoxin B1 was more potent that G1, both mycotoxins significantly inhibited enzyme activity in a concentration-dependent fashion.     

Biotransformation of the flame retardant tetrabromo-bisphenol A by human and rat sub-cellular liver fractions

The comparative in vitro metabolism of the flame retardant tetrabromo-bisphenol A was studied in rat and human using a [(14)C]-radio-labelled molecule. Tetrabromo-bisphenol A is metabolised into the corresponding glucuronide (liver S9 fractions) and several other metabolites produced by cytochrome P450 dependent pathways (liver microsomes and liver S9 fractions). No major qualitative differences were observed between rat and human, regardless of the selected concentration, within the 20-200 microM range. Tetrabromo-bisphenol A undergoes an oxidative cleavage near the central carbon of the molecule, that leads to the production of hydroxylated dibromo-phenol, hydroxylated dibromo-isopropyl-phenol and glutathione conjugated dibromo-isopropyl-phenol. The main metabolites of tetrabromo-bisphenol A are two molecules of lower polarity than the parent compound, characterised as a hexa-brominated compound with three aromatic rings and a hepta-brominated dimer-like compound, respectively. Both structures, as well as the lower molecular weight metabolites resulting from the breakdown of the molecule, suggest the occurrence of chemically reactive intermediates formed following a first step oxidation of tetrabromo-bisphenol A.     

In vitro effect of dimethoate on the activity of tryptophan pyrrolase in rat liver

Total and holo-enzyme activities of tryptophan 2,3-dioxygenase were measured in vitro in the presence and absence of the organophosphorous insecticide, dimethoate. Addition of dimethoate to the reaction mixture decreased the activities of both total and holo-forms. Total and holo-enzyme activities were decreased by 34% and 26%, respectively, by 1 mM dimethoate. On the other hand, 5 mM dimethoate resulted in 56% and 34% inhibition to total and holo-enzyme activities, respectively. Lineweaver-Burk plot of the total-enzyme activity at different tryptophan concentration in the presence of 2 mM dimethoate gave uncompetitive type of inhibition.     

Pure non-dioxin-like PCB congeners suppress induction of AhR-dependent endpoints in rat liver cells

The relative potencies of non-ortho-substituted coplanar polychlorinated biphenyl (PCB) congeners to activate the aryl hydrocarbon receptor (AhR) and to cause the AhR-dependent toxic events are essential for their risk assessment. Since some studies suggested that abundant non-dioxin-like PCB congeners (NDL-PCBs) may alter the AhR activation by PCB mixtures and possibly cause non-additive effects, we evaluated potential suppressive effects of NDL-PCBs on AhR activation, using a series of 24 highly purified NDL-PCBs. We investigated their impact on the model AhR agonist-induced luciferase reporter gene expression in rat hepatoma cells and on induction of CYP1A1/1B1 mRNAs and deregulation of AhR-dependent cell proliferation in rat liver epithelial cells. PCBs 128, 138, and 170 significantly suppressed AhR activation (with IC₅₀ values from 1.4 to 5.6 μM), followed by PCBs 28, 47, 52, and 180; additionally, PCBs 122, 153, and 168 showed low but still significant potency to reduce luciferase activity. Detection of CYP1A1 mRNA levels in liver epithelial cells largely confirmed these results for the most abundant NDL-PCBs, whereas the other AhR-dependent events (CYP1B1 mRNA expression, induction of cell proliferation in confluent cells) were less sensitive to NDL-PCBs, thus indicating a more complex regulation of these endpoints. The present data suggest that some NDL-PCBs could modulate overall dioxin-like effects in complex mixtures.     

Involvement of glutathione in the reduction of captan-induced in vivo inhibition of monooxygenases and liver toxicity in the rat

If given orally captan is relatively nontoxic, but it can be extremely toxic after parenteral exposure. Therefore, a single i.p. dose of captan (20 mg/kg) was given to male Sprague-Dawley rats and its effect on liver microsomal mixed function oxidases and certain serum enzymes (SDH, SGPT and SGOT) was studied. The single dose of captan caused marked depression of microsomal cytochrome P-450 and the activity of benzphetamine N-demethylase and aniline hydroxylase, and moderate elevation of the serum enzymes indicative of liver damage. However, reduced glutathione (100 mg/kg, i.p.) given prior to captan, appears to decrease the liver toxicity as measured by reduced inhibition of the microsomal enzymes and elevation of serum enzymes activity. The results suggest that glutathione and other compounds containing sulfhydryl groups may protect the subjects from captan-induced liver toxicity.     

Deleterious effects of cypermethrin on rat liver and kidney: protective role of sesame oil

The involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides. Our study was designed to investigate the induction of oxidative stress by cypermethrin; a Type II pyrethroid in rat liver and kidney. In addition, the protective role of sesame oil against the toxicity of cypermethrin was investigated. Animals were divided into four equal groups; the first group used as control while groups 2, 3 and 4 were treated with sesame oil (5 mL/kg b.w), cypermethrin (12 mg/kg b.w) and the combination of both sesame oil (5 mL/kg b.w) plus cypermethrin (12 mg/kg b.w), respectively. Rats were daily administered with their respective doses for 30 days by gavage. Repeated oral administration of cypermethrin was found to reduce the level of glutathione (GSH) and the activities of the antioxidant enzymes. While, the level of TBARS was elevated indicating the presence of oxidative stress. The activities of LDH, AST and ALT were decreased in the liver extract while increased in the plasma of the cypermethrin-treated group. Also, the levels of urea and creatinine were significantly increased after treatment with cypermethrin. Liver and kidney injury was confirmed by the histological changes. In conclusion, the administration of sesame oil provided significant protection against cypermethrin-induced oxidative stress, biochemical changes, histopathological damage and genomic DNA fragmentation.     

Deleterious effects of cypermethrin on rat liver and kidney: Protective role of sesame oil

The involvement of reactive oxygen species (ROS) has been implicated in the toxicity of various pesticides. Our study was designed to investigate the induction of oxidative stress by cypermethrin; a Type II pyrethroid in rat liver and kidney. In addition, the protective role of sesame oil against the toxicity of cypermethrin was investigated. Animals were divided into four equal groups; the first group used as control while groups 2, 3 and 4 were treated with sesame oil (5 mL/kg b.w), cypermethrin (12 mg/kg b.w) and the combination of both sesame oil (5 mL/kg b.w) plus cypermethrin (12 mg/kg b.w), respectively. Rats were daily administered with their respective doses for 30 days by gavage. Repeated oral administration of cypermethrin was found to reduce the level of glutathione (GSH) and the activities of the antioxidant enzymes. While, the level of TBARS was elevated indicating the presence of oxidative stress. The activities of LDH, AST and ALT were decreased in the liver extract while increased in the plasma of the cypermethrin-treated group. Also, the levels of urea and creatinine were significantly increased after treatment with cypermethrin. Liver and kidney injury was confirmed by the histological changes. In conclusion, the administration of sesame oil provided significant protection against cypermethrin-induced oxidative stress, biochemical changes, histopathological damage and genomic DNA fragmentation.     

Biosurfactant electrospun nanofibers exhibit minimal side effects on the structure and function of the liver tissue in male rat model

Environmental Science and Pollution Research - Oil spills can result in significant damage to marine estuaries, rivers, lakes, wetlands, and shorelines. Electrospun nanofibers containing...     

1,2,3,5,6,7-Hexachloronaphthalene and 1,2,3,4,6,7-hexachloronaphthalene - selective retention in rat liver and appearance in wildlife

The two isomers 1,2,3,5,6,7- and 1,2,3,4,6,7-hexachloronaphthalene are shown to be selectively retained in the liver of rats orally dosed with the commercial PCN product Halowax 1014. The retention was further studied by dosing rats orally with a mixture of the two compounds. The rats were sacrificed after 1, 10, 35 and 120 days, respectively. The two hexachloronaphthalenes were found to be strongly retained in the liver and the concentration ratios liver/adipose tissue were remarkably high. 1,2,3,5,6,7- And 1,2,3,4,6,7-hexachloronaphthalene were also found to be present in two environmental samples from the Swedish east coast, cod liver and guillemot egg.     

Anti-oxidant and hepatoprotective effects of Salvia officinalis essential oil against vanadium-induced oxidative stress and histological changes in the rat liver

Environmental Science and Pollution Research - The present study was designed to evaluate the protective effects of Salvia officinalis essential oil (SOEO) against vanadium-induced hepatotoxicity...     

4-Alkylphenols and related chemicals show similar effect on the function of human and rat estrogen receptor alpha in reporter gene assay

Alkylphenols (APs) are widely used as important industrial materials and have attracted lots of attention because of their potential estrogenic activities. In this study, we developed human estrogen receptor alpha (hERalpha) and rat estrogen receptor alpha (rERalpha) mediated reporter gene assays and compared the estrogenic activity of APs and related chemicals based on the two ERalpha. Human breast cancer cell line MCF-7 was co-transfected with Gal4-fused hERalpha and corresponding reporter plasmid; African green monkey kidney cell line CV-1 was co-transfected with rERalpha and reporter gene. Both assays showed acceptable response to natural estrogen 17beta-estradiol (E2) with EC50 of 0.16 nM and 4.7 nM. Then the estrogenic activity of 4-APs, 4-phenylphenol and bisphenol-A were evaluated and compared with the effects of E2. The data suggested that test APs and related chemicals possessed weakly estrogenic activity and the activity of test APs increased with the increase of substituent size. This structure-activity relationship helped to infer the activity of chemicals with similar feature. Furthermore, test APs showed similar effect on the function of hERalpha and rERalpha. This consistency helped to extrapolate in vivo rodent data to human being when performing risk assessment of endocrine disruptors.     

The interaction of 1,3-diaryltriazenes with the receptor

Certain substituted 1,3-diaryltriazenes possessing anorectic activity were evaluated for their ability to compete with ³H-TCDD for specific binding to the receptor. The N-substituent had little effect while aromatic substitution was important in determining binding to the receptor.     

Development of an immuno-immobilized androgen receptor assay (IRA) and its application for the characterization of the receptor binding affinity of different pesticides

Pesticides are synthetic chemicals used not only for improving food and feed production but also for the protection of materials and of human health and well-being. Some of these substances are suspected for adverse effects attributable to an interaction with the endocrine system of vertebrates by mimicking or inhibiting endogenous hormones. One of the biological targets important in this relation is the androgen receptor (AR). To be able to screen environmental samples for the presence of compounds which might interfere with androgen action, we aimed to develop a receptor assay based on recombinant human AR (rhAR). We herein describe an rhAR assay in which the receptor is immobilized in microtiter plates via a specific antibody. The assay can be used for high throughput screening of chemicals spread into the environment. 29 of the most recommended pesticides of the Federal Country Hessen, Germany, were tested for their ability to displace [3H]-DHT bound to the rhAR. This evaluation included the major part of the most common herbicides, insecticides and fungicides and covered three potential groups of endocrine disrupting chemicals. For 28 of the substances evaluated, the relative binding affinity to the rhAR was below 0.1% when compared to dihydrotestosterone (DHT) (100%), only fentinacetate exhibited an affinity of 1.42%. An exchange assay indicated that the binding inhibition was reversible. In consequence, fentinacetate seems to be a hormonally active substance which may be present in vegetables or fish, but also on clothing. We conclude that further investigations on this compound and its metabolites are necessary.     

Effect of selected pesticides and their ozonation by-products on gap junctional intercellular communication using rat liver epithelial cell lines.

The non-genotoxic effects of two commonly used pesticides, 1,1-bis (p-chlorophenyl)-2,2,2-trichloroethane (DDT) and malathion, and one widely used commercial insect repellent N,N-diethy-m-toluamide (DEET) on gap junction intercellular communication (GJIC) were determined using a rat liver epithelial cell line. Malathion and DDT reversibly inhibited GJIC in a treatment time- and dose-dependent manner at non-cytotoxic doses, whereas, DEET did not inhibit GJIC. Malathion was very reactive with ozone, while DEET and DDT did not react to any appreciable extent with ozone. The mixtures of ozonation products from malathion and DEET did not inhibit GJIC. The mixtures of ozonation by-products formed from DDT inhibited GJIC, but to a lesser extent than did DDT, itself. These results suggest that ozone can effectively remove malathion from solution without forming GJIC-toxic products, but is less effective in eliminating DEET and DDT from solution.     

The metabolism of 2,3,7,8-tetrachlorodibenzofuran in the rat

Single doses of 2,3,7,8-tetrachlorodibenzofuran (2378-TCDF) were administered orally to bile duct cannulated rats and bile collected for up to 48 hours. The bile was analysed for the parent compound and metabolites. In organic extracts, which had been methylated and purified by TLC, 13 chlorinated metabolites were detected that were not present in the bile of untreated animals. Four of these, tetrachloromethoxy-, trichloromethoxy-and two trichlorodimethoxy-dibenzofuran isomers were present in major amounts. The remaining compounds, found only in minor or trace amounts very likely originate from other chlorinated dibenzofurans present as impurities in 2378-TCDF. No parent compound was detected in these samples.     

Arsenic accumulation in the liver tissue of marine mammals.

Arsenic concentrations were determined in livers of 226 individuals representing 16 different marine mammal species to elucidate its accumulation with age, sex, and feeding habits. Arsenic concentrations varied widely among species and individuals, and ranged from < 0.10 to 7.68 micrograms g-1 dry weight. Marine mammals feeding on cephalopods and crustaceans contained higher arsenic concentrations than those feeding on fishes. No significant gender difference in arsenic concentration was found for almost all the species. Also, no apparent trend with age (or body length) in arsenic accumulation was found for most of the species. It was noted that two seal species, Baikal seal and Caspian seal, from landlocked water environments, contained lower arsenic concentrations than the marine species. To our knowledge, this is the first comprehensive study of arsenic accumulation in a wide range of marine mammal species.     

Excretion and toxicity of Cyolane in the rat

The excretion of ¹⁴C-labelled Cyolane, 24 hours after single oral application was found to be about 50% of the applied dose in urine, faeces and expired air.The activity of Acetylcholine esterase in brain, plasma and erythrocytes, and liver succinate dehydrogenase was studied for 16 weeks in 4 groups of rats after repeated orally daily doses of Cyolane, 0.9, 0.45, 0.09 and 0.045 mg/kg.It has been found that at all the dose levels there were cumulative inhibition effects in brain and blood choline esterase and liver succinate dehydrogenase till the 2nd week and then there was a recovery at low dose rates in blood choline esterase and liver succinate dehydrogenase activities. After 6 - 16 weeks the effects were nearly compensated. At higher doses almost all the rats died after 6 weeks due to the insecticide toxicity.     

Review of receptor model fundamentals

There are several broad classes of mathematical models used to apportion the aerosol measured at a receptor site to its likely sources. This paper surveys the two types applied in exercises for the Mathematical and Empirical Receptor Models Workshop (Quail Roost II): chemical mass balance models and multivariate models. The fundamental principles of each are reviewed. Also considered are the specific models available within each class. These include: tracer element, linear programming, ordinary linear least-squares, effective variance least-squares and ridge regression (all solutions to the chemical mass balance equation), and factor analysis, target transformation factor analysis, multiple linear regression and extended Q-mode factor analysis (all multivariate models). In practical application of chemical mass balance models, a frequent problem is the presence of two or more emission sources whose signatures are very similar. Several techniques to reduce the effects of such multicollinearity are discussed. The propagation of errors for source contribution estimates, another practical concern, also is given special attention.     

Accumulation of silver in the liver of three species of pinnipeds

Silver in the three species of pinnipeds [northern fur seal (Callorhinus ursinus), Steller sea lion (Eumetopias jubatus), and harbor seal (Phoca vitulina)] caught in the North Pacific Ocean were analyzed using inductively coupled plasma-mass spectrometry, in order to understand accumulation and distribution of silver in pinnipeds. In northern fur seals, relatively high concentrations of silver were observed in the liver and body hair. Some 70% of the silver burden was concentrated in the liver. Hepatic silver concentrations were significantly correlated to age in northern fur seals (r = 0.766, P < 0.001, n = 49) and Steller sea lions (r = 0.496, P < 0.01, n = 28). Levels of silver concentrations per wet weight (microgram g-1) in the three pinnipeds ranged from 0.04 to 0.55 for northern fur seals, from 0.1 to 1.04 for Steller sea lions and from 0.03 to 0.83 for harbor seals. Silver concentrations in liver for all pinnipeds were significantly correlated with mercury, and selenium (P < 0.001). Molar ratios between silver to selenium approximated 1:180 in northern fur seals, 1:120 in Steller sea lions, and 1:60 in harbor seals. The silver-mercury molar ratios were approximately 1:170 in northern fur seals, and 1:80 both in the other species. Increase in silver accumulation in the liver was caused by the retention in nuclei and mitochondria fraction together with mercury and selenium in the cells of northern fur seals.