bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of kola‐nut extract administration on the liver, kidney, brain, testis and some serum constituents of the rat
Authors: Ikegwuonu F. I. , Aire T. A. , Ogwuegbu S. O. 
Published: October 2006

AbstractKola‐nut extract induced a number of overt neurotoxicological signs in male albino rats. A decrease in the total body weight and an increase in the absolute weights of the liver, kidney, brain and testis were observed after 18 weeks oral administration of kola‐nut extract to the rats. Total protein, RNA and DNA of these organs were significantly depressed. The activity of β‐glucuronidase and β‐galactosidase was induced only in the kidney, brain and testis of treated animals. While the levels of serum phosphomonoesterases and total cholesterol were significantly enhanced due to kola‐nut intake, serum total and conjugated bilirubin levels were significantly decreased.
Electrospun polyphosphazene nanofibers for in vitro rat endothelial cells proliferation
Authors: Carampin Paolo , Conconi Maria Teresa , Lora Silvano , Menti Anna Michela , Baiguera Silvia , Bellini Silvia , Grandi Claudio , Parnigotto Pier Paolo 
Published: October 2006

AbstractA large variety of natural and synthetic polymers have been explored as scaffolds for the seeding and growth of different types of cells. To fabricate a scaffold that can be used as a synthetic extracellular matrix (ECM), it is important to replicate the nanoscale dimensions of natural ECM. The electrospinning process allows to produce ultrathin fibers so that this method represents a suitable approach to scaffold fabrication for tissue engineering applications. In this work, the feasibility of obtaining flat or tubular matrices from biocompatible poly[(ethyl phenylalanato)1.4 (ethyl glycinato)0.6 phosphazene] by electrospinning was evaluated and the effect of process parameters on the diameter of nanofibers was examined. The adhesion and growth of rat neuromicrovascular endothelial cells cultured on sheets and tubes composed by the polymer with an average fiber diameter of 850 ± 150 nm were also reported. Microscopic examination of the seeded tubes demonstrated that, after 16 days of incubation, endothelial cells formed a monolayer on the whole surface. These results are the first step to demonstrate that tubes of biodegradable polyphosphazenes might be a feasible model to construct human tissues such as vessels or cardiac valves. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
Detection of in vivo lipid peroxidation using the thiobarbituric acid assay for lipid hydroperoxides
Authors: Kirkpatrick Daniel T. , Guth Daniel J. , Mavis Richard D. 
Published: October 2006

AbstractThiobarbituric acid (TBA) assays which have been modified for detection of lipid hydroperoxides appear to be useful for demonstration of in vivo lipid peroxidation. Since these methods require heating tissue membranes with the buffered TBA, there is a possibility of interference from the detection of autoxidation that occurs during heating. These studies were undertaken to investigate conditions which favor TBA color production from hydroperoxide while limiting autoxidation during the assay. An acetic acid‐sodium acetate buffered (pH 3.6) TBA assay was used. Heating linoleic acid hydroperoxide with 50 μM ferric iron or under nitrogen nearly doubled color production compared to heating it with no added iron or under air. The lipid antioxidant butylated hydroxytoluene inhibited color production from fatty acid hydroperoxides. When tissue fractions, including liver and lung microsomes and lung whole membranes, were heated in the assay, color production was greater under air than under nitrogen and was much greater under oxygen. When liver microsomes from carbon tetrachloride‐exposed rats were used, color was increased only when oxygen was present in the heating atmosphere. The results with tissue fractions appear to demonstrate autoxidation during color development rather than the presence of preformed hydroperoxides. Finally, it was found that color production from membrane fractions was dependent on the vitamin E content of the membranes. It appears that autoxidation during heating should be limited by heating under nitrogen and not by adding antioxidants, which inhibit color production from hydroperoxides. As the vitamin E effect demonstrates, antioxidant status must be considered, since a change in color production could result from a change in antioxidant content without the accumulation of lipid hydroperoxides.
Potentiation by chlordecone of the defect in hepatic microsomal calcium sequestration induced by carbon tetrachloride
Authors: Hegarty Joel M. , Glende Eric A. , Recknagel Richard O. 
Published: October 2006

AbstractThe effect of carbon tetrachloride (CCl4) on the capacity of hepatic microsomes to sequester calcium was studied following pretreatment of rats with chlordecone. Chlordecone pretreatment alone had no effect on the kinetics of calcium uptake by hepatic microsomes. It was found, however, that chlordecone pretreatment of rats potentiated by sixfold the potency of CCl4 to suppress microsomal calcium sequestration capacity when measured one hour after CCl4 administration.
The in vitro metabolism and bioactivation of 1,2‐dibromoethane (ethylene dibromide) by human liver
Authors: Wiersma David A. , Schnellmann Rick G. , Sipes I. Glenn 
Published: October 2006

AbstractThe nematocide, grain fumigant, and gasoline additive 1,2‐dibromoethane (DBE) is both a cellular and a genetic toxin that is metabolically activated in rats and mice by mixed function oxidases (MFO) as well as glutathione S‐transferases (GST). The purpose of this study was to determine whether DBE is similarly metabolized and bioactivated by human liver in vitro.Human liver microsomal and cytosolic metabolism of DBE was monitored by the production of aqueous‐soluble metabolites from [14‐C]‐DBE. Reactive intermediates were detected as irreversibly bound adducts to protein or DNA. 1,2‐Dibromoethane was metabolized by human liver cytosolic GST, microsomal GST, and microsomal MFO. Cytosolic GST activity (9 ± 2 nmol/20 min/mg protein) was about four times greater than the other two activities. Only MFO activity resulted in adducts irreversibly bound to protein (1.5 ±.4 nmol/20 min/mg protein) and was inhibited by the presence of glutathione. Both MFO and GST activity resulted in irreversibly bound adducts to DNA. Microsomal and cytosolic GST activity each produced about twice as many DNA adducts as microsomal MFO activity.These results suggest that human liver, like rat and mouse liver, metabolizes DBE to aqueous‐soluble metabolites by both MFO and GST activity. Furthermore, each of these activities produces reactive metabolites that can irreversibly bind to cellular macromolecules.
In vivo and in vitro synthesis, release, and uptake of [3‐H]‐dopamine in mouse striatal slices after in vivo exposure to chlordecone
Authors: Fujimori Kannosuke , Benet H. , Mehendale H. M. , Ho I. K. 
Published: October 2006

AbstractEffects of treatment of mice with chlordecone (25 mg/kg/d) on striatal dopaminergic activities such as synthesis, turnover, uptake, and release were investigated in vivo and in vitro. In mice receiving chlordecone for five days, there were no significant changes in in vivo dopamine (DA) synthesis and turnover in striatum and in vitro [3‐H]‐dopamine uptake and K+‐stimulated [3‐H]‐dopamine release in striatal slices. In mice receiving chlordecone for eight days, the in vivo synthesis of [3‐H]‐dopamine from [3‐H]‐tyrosine in striatum was slightly inhibited and the in vitro [3‐H]‐dopamine synthesis in striatal slices was significantly decreased. Furthermore, both uptake and K+‐stimulated release of [3‐H]‐dopamine from striatal slices were significantly reduced. The turnover rate of newly synthesized [3‐H]‐dopamine from [3‐H]‐tyrosine in striatal slices was unchanged after eight consecutive days of chlordecone administration. These results suggest that chlordecone may cause impairments in pre‐ and/or postsynaptic membranes of dopaminergic neurons which modulate motor function.
Immunochemical characterization of human lung epoxide hydrolases
Authors: Guenthner Thomas M. , Karnezis Thomas A. 
Published: October 2006

AbstractImmunochemical techniques were used to investigate the biochemical properties of human lung epoxide hydrolases. Two epoxide hydrolases with different immunoreactive properties were identified. These two epoxide hydrolases were found in both cytosolic and microsomal cell fractions. Immunotitration of enzyme activity showed that enzymes that catalyze the hydration of benzo(a)pyrene 4,5‐oxide react with antiserum to rat microsomal epoxide hydrolase; those that hydrate trans‐stilbene oxide do not. Immunotitration and Western blot experiments showed that microsomal and cytosolic benzo(a)pyrene 4,5‐oxide hydrolases have significant structural homology. Immunohistochemical staining of human lung benzo(a)pyrene 4, s‐oxide hydrolase showed that the enzyme is localized primarily in the bronchial epithelium. No cell type‐specific localization was observed. An enzyme‐linked immunosorbent assay was developed which allows direct quantitation of benzo(a)pyrene 4,5‐oxide hydrolase protein. Levels of enzyme protein detected by this assay correlated well with enzyme levels determined by substrate conversion assays.
2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin causes elevation of the levels of the protein tyrosine kinase pp60c‐src
Authors: Bombick David W. , Matsumura Fumio 
Published: October 2006

Abstract2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) has been found to cause increases in cellular levels of pp60src, a protein tyrosine kinase in hepatocytes from the rat and guinea pig, in the thymus of the mouse in vivo and in NIH‐3T3 mouse fibroblast cell lines in vitro. Such cellular changes take place in vivo at early stages of TCDD poisoning (as early as one day after treatment in the case of mouse thymus) and at very low doses (single intraperitoneal injections of 1 μg/kg for guinea pigs, 25 μg/ kg for rats, and 30 μg/kg for mice). In addition such an effect of TCDD was observed only in a TCDD‐responsive mouse strain but not in a nonresponsive strain. This effect of TCDD is a long‐lasting one (eg, even 25 days after single dosing, the levels of pp60src in the hepatic membrane remained high). In vitro this effect was observed in a wild‐type 3T3 cell line but was more pronounced in one of the transfected lines with a v‐src gene, a virus‐derived oncogene known to code for pp60src protein.
Possible antiestrogenic activity of lindane in female rats
Authors: Chadwick Robert W. , Cooper Ralph L. , Rehnberg Georgia L. , McElroy W. Keith , Chang Jerjang 
Published: October 2006

AbstractDuring chronic peroral (PO) treatment of weanling, female Fischer 344 rats with daily injections (0.069 mmol/kg) of either 1,1′‐(2,2,2‐trichloroethylidene) bis [4‐chlorobenzene] (p,p′‐DDT), 2,4‐dichlorophenoxy acetic acid (2,4‐D), or γ‐hexachlorocyclohexane (lindane), the lindane treatment induced a significant 20% increase in body weight after 110 days. Further investigation with 0,5,10,20, and 40 mg/kg lindane confirmed a significant increase in average body weight gain at the two highest doses after ten weeks of treatment. Significantly greater food consumption was observed, and the Lee index indicated that lindane treatment induced obesity. In addition to obesity, lindane caused a delay in vaginal opening, disrupted estrous cycling, reduced pituitary and uterine weight, and elevated food consumption during proestrus (when appetite is normally suppressed by estradiol). These responses suggest that, by inducing alterations in the reproductive function of the female rat and by interfering with hormonal regulation of energy balance, lindane may be antiestrogenic rather than estrogenic as previously proposed.
Neuropathy target esterase in hens after sarin and soman
Authors: Crowell J. A. , Parker R. M. , Bucci T. J. , Dacre J. C. 
Published: October 2006

AbstractTo estimate the potential of small doses of sarin (types I and II) and soman to cause delayed neuropathic effects, 400, 200, 61, and 0 μg/kg of sarin‐I, 280, 140, 70, and 0 μg/kg of sarin‐II, and 14.2, 7.1, 3.5, and 0 μg of soman by gavage were compared with 510 mg/kg tri‐o‐cresyl phosphate (TOCP) in 14‐to 18‐month‐old SPF white leghorn hens (4/dose) protected with atropine (100 mg/kg). The neuropathy target esterase (NTE) activity 24 hr after dosing was determined in brain, spinal cord, and lymphocytes and in plasma and brain for cholinesterase and carboxylesterase. None of the compounds showed statistically significant NTE decreases. Sarin‐II showed a dose‐related trend in the lymphocyte NTE (to 33% of control at 280 μg/kg), suggesting that longer exposure to lower doses might cause a cumulative neurotoxic insult. All of the agents decreased the activity of plasma and brain cholinesterase and carboxylesterase. Using more than 70% inhibition of brain NTE as a biochemical predictor of delayed neuropathy, sarin and soman appear unable to cause delayed neuropathy at nonlethal doses within this protocol.
Subacute inhalation of cigarette smoke by pregnant and lactating rodents: Ahh changes in perinatal tissues
Authors: Bilimoria M. H. , Ecobichon D. J. 
Published: October 2006

AbstractTo study the transplacental acquisition of tobacco smoke products and the effects on fetal tissue enzymes, pregnant rats, guinea pigs, and hamsters were exposed to freshly generated cigarette smoke via a nose‐only inhalation system on a daily basis through the latter one‐third (guinea pigs) or latter half (rats, hamsters) of the gestational period. Following euthanasia on the day of parturition, micro‐somal aryl hydrocarbon hydroxylase (AHH) activities were determined in the lungs, livers, and kidneys of both dams and fetuses. The possible acquisition of tobacco smoke products via the milk was studied by exposing lactating dams to cigarette smoke daily for either 4 or 14 days (rats), 4 or 7 days (guinea pigs), or 10 days (hamsters), with analysis of tissues from the euthanized pups for AHH. Pups were also exposed directly (nose only) to cigarette smoke. In the treated pregnant and lactating rat, maternal pulmonary, hepatic, and renal AHH was significantly increased but only fetal lung and the liver of 14‐day‐old pups showed a marked induction of AHH activity. In the pregnant and lactating guinea pig, only the pulmonary and renal AHH activities were increased following exposure, whereas in the fetuses and nursing pups, none of the tissue AHH activities was significantly altered by exposure. In the pregnant and lactating hamster, only the pulmonary AHH was increased following exposure to cigarette smoke, whereas the activity in fetal and pup tissues remained unchanged from the levels observed in control animals. Direct exposure of 7‐and 14‐day‐old rat pups to cigarette smoke resulted in a significant induction of AHH in lung, liver, and kidney at both ages. In the 7‐and 14‐day‐old hamster pups, increased AHH activity was measured only in the lungs of 14‐day‐old animals. In the guinea pip pups at 2 days of age, AHH levels were increased significantly only in the kidney.
Induction of cytochrome p‐450 isozymes by mirex and chlordecone
Authors: Lewandowski Margaret , Levi Patricia , Hodgson Ernest 
Published: October 2006

AbstractThe effect of the insecticides, mirex and chordecone (Kepone), on the cytochrome P‐450 monooxygenase system in C57BL/6N mouse liver microsomes was studied. Mice were treated intraperitoneally with low (6 mg/kg) and high (30 mg/kg) doses of mirex and chlordecone in corn oil for 2 days. For comparison, mice were also treated with either phenobarbital (PB) or 3‐methylcholanthrene (3‐MC). All treatments significantly increased the hepatic microsomal P‐450 content over that of controls. Benzphetamine N‐demethylase, ethoxyresorufin O‐deethylase, benzo[a]pyrene hydroxylase, and acetanilide hydroxylase activities were also determined. Mirex and chlordecone resembled phenobarbital with respect to the induction of monooxygenase activities. Immunoquantitation with antibodies to purified P‐450 IIB1 (Pb‐induced P‐450) and P‐450 IA1 (3‐MC‐induced P‐450) indicated that mirex and chlordecone induced P‐450 IIB1 in a dose‐dependent manner. The high dose of mirex also induced a small amount of a protein cross reacting with the antibody to IA1. The induction of this isozyme did not, however, contribute significantly to the monooxygenase activities measured.
Hepatic Ah Receptor from the Wistar Rat: Role of Solvation in Receptor Structure and Inactivation
Authors: Landers James P. , Bunce Nigel J. 
Published: October 2006

AbstractRepeated freezing and thawing, the addition of salts, and elevated temperatures all promote the inactivation of the rat hepatic Ah receptor. The reduced availability of bulk water to solvate the protein is proposed to be the factor linking all these routes for inactivation. Prospective protocols for purification of unliganded Ah receptor should therefore minimize the number of freeze/thaw cycles; long‐term freezing of cytosolic samples at −20°C is inadequate to maintain long‐term viability of the unliganded receptor. The stability of rat hepatic receptor is greatly increased upon binding the ligand, and the extent of ligand‐induced stabilization is much greater than what is observed with steroid hormone receptors. Concentrations of NaCl and K2HPO4 up to 0.5 M inactivate the unbound Ah receptor irreversibly, with the loss of approximately 50% of the specific binding. At 2.0 M NaCl, a further reversible reduction in ligand binding activity is observed. The results at lower salt concentrations are interpreted in terms of the irreversible dissociation of a single binding unit from the trimeric cytosolic Ah receptor (which consists of two ligand‐binding units and a 90‐kDa heat shock protein), with the release of bound ligand from that subunit.
Induction of drug metabolism enzymes by dihalogenated biphenyls
Authors: van Bree L. , Commandeur J. , Lamberts B. , Cornelissen M. , van Roon M. , Laterveer H. , de Vries J. 
Published: October 2006

AbstractThe effects of pretreatment with symmetrically dihalogenated biphenyls (DXBs, X‐F, Cl(C), Br(B) and I) on rat liver drug metabolism enzymes were investigated. 4,4′‐DFB, ‐DCB, and ‐DBB as well as 2,2′‐DFB appeared to be inducers of microsomal cytochrome P‐450‐linked monoxygenases (N‐demethylases of aminopyrine and ethylmorphine). However, no structure‐induction relationship was found. 4,4′‐DXBs also induced a cytochrome P‐448‐linked mono‐oxygenase (ethoxyre‐sorufin O‐deethylase), and their order of induction potential seemed to parallel the increase of the size of the halogen substituent. Therefore, 4,4′‐DXB's may be categorized as mixed‐type inducers, the cytochrome P‐450 component being the more pronounced. Data on the cytochrome P‐448 induction by dihalogenated biphenyls with only para substituents may be considered as a refinement of the previously described structure‐activity relationship in this respect. All of the DXBs except 3,3′‐DCB and 4,4′‐DIB, enhanced, like phenobarbital, the activity of UDP‐glucuronyltransferase toward 4‐hydroxybiphenyl. Only 4,4′‐DFB was able to induce the activity of glutathione S‐transferase toward 1,2‐epoxy‐3‐(p‐nitrophenoxy)propane. Studies after 4,4′‐DBB‐treatment revealed, like phenobarbital, a preferential induction of ethylmorphine N‐demethylase on rough endoplasmic reticulum‐derived microsomes, whereas UDP‐glucuronyltransferase activity toward 4‐hydroxybiphenyl was induced to a larger extent on smooth endoplasmic reticulum microsomes, suggesting a dissimilar enzyme induction in microsomal subfractions.
The Interference of Aroclor 1254 with Progesterone Metabolism in Guinea Pig Adrenal and Testes Microsomes
Authors: Goldman Daphne , Yawetz Aminadav 
Published: October 2006

AbstractThe effects of Aroclor 1254 on cytochrome P‐450‐mediated steroidogenic activities were investigated in adrenal and testis microsomes of male guinea pigs. A significant decrease was recorded in the tissue content of adrenal microsomal cytochrome P‐450 as well as a significant reduction in the overall conversion of progesterone to steroid products., The effects of exposure to Aroclor 1254 on activities of cytochrome P450 21‐hydroxylase and cytochrome P450 17α‐hydroxylase /C17,20‐lyase were selective. Cytochrome P‐450 21‐Hydroxylase activity was inhibited, as reflected by a decrease in production of 11‐deoxycortisol and 11‐deoxycorticosterone, whereas the cytochrome P‐450 17α‐hydroxylase / C17,20‐lyase activities, represented by the production of 17α‐hydroxyprogesterone and androstenedione were elevated. The same and even more pronounced pattern of altered progesterone metabolism elicited by Aroclor 1254 was observed in vitro, when Aroclor 1254 was introduced into incubation mixtures prepared with adrenal microsomes from untreated animals. Under such experimental conditions, a decrease in the overall metabolism of progesterone was observed as well as a decrease in cytochrome P‐450 21‐hydroxylase activity, while there was significant elevation in the 17α‐hydroxylase /C17,20‐lyase activities.The effect of Aroclor 1254 on the testes differed largely from its effect on the adrenal cortex. In testis microsomes, pretreatment with Aroclor 1254 resulted in no changes in the cytochrome P‐450 content, contrary to the decrease observed in adrenal microsomes. In contrast to its inductive effect on the normally suppressed androgen producing pathway in adrenal microsomes, Aroclor 1254 had no effect on the 17‐hydroxylase /C17,20‐lyase activities in testis microsomes, both in the pretreated animals as well as when it was present in the incubation mixtures containing microsomes of untreated animals. The results of this study indicate a difference in the response of steroidogenic tissues to Aroclor 1254. In adrenal microsomes Aroclor 1254 may have modulated the steroidogenic activities at a posttranscriptional level, possibly by interfering with membrane regulation of these metabolic activities. At the same time, the results obtained do not exclude the possibility that Aroclor 1254 alters the composition of cytochrome P‐450 isozymes present in adrenal tissue.
Aflatoxin B1 metabolism by 3‐methylcholanthrene‐induced hamster hepatic cytochrome P‐450s
Authors: Lai T. S. , Chiang J. Y. L. 
Published: October 2006

AbstractWe have studied the activation of aflatoxin B1 by hamster liver microsomes and purified hamster cytochrome P‐450 isozymes using a umu mutagen test. The hamster liver microsomes or S‐9 fractions were much more active than rat liver microsomes or S‐9 fractions in the activation of umu gene expression by aflatoxin B1 metabolites. 3‐Methylcholanthrene treatment increased aflatoxin B1 activation by hamster liver microsomes. Two major 3‐methylcholanthrene‐inducible cytochrome P‐450 isozymes, P‐450 MC1 (IIA) and P‐450 MC4 (IA2), were purified from 3‐methylcholanthrene‐treated hamster liver microsomes, and the metabolism of aflatoxin B1 by these two cytochromes was studied. In the reconstituted enzyme system, both P‐450 MC1 and P‐450 MC4 were highly active in the activation of aflatoxin B1, and antibodies against these P‐450s specifically inhibited these activities. Antibody against P‐450 MC1 inhibited the activation of aflatoxin B1 by 20% in the presence of 3‐methylcholanthrene‐treated hamster liver microsomes. In contrast, antibody against P‐450 MC4 stimulated the activity by 175%. These results indicated that hamster P‐450 MC1 might convert aflatoxin B1 to more toxic metabolite(s), whereas P‐450 MC4 might convert aflatoxin B1 to less toxic metabolite(s), than aflatoxin B1 in liver microsomes. The metabolite(s) produced by both hamster cytochrome P‐450 MC1 and MC4 were genotoxic in the umu mutagen test.