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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 70 (1996), S. 714-723 
    ISSN: 1432-0738
    Keywords: Key words 1 ; 2-Dichlorobenzene (o-DCB) ; Straindifferences ; Dose-response ; Tissue repair ; Ultimate outcome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Fischer 344 (F344) rats are reportedly 75-fold more sensitive than Sprague Dawley (S-D) rats to 1,2-dichlorobenzene (o-DCB) hepatotoxicity. Lethality studies were conducted since no information was available regarding the ultimate consequence of this sensitivity in terms of animal survival in the two strains. LD50s for o-DCB (1.66 ml/kg and 1.76 ml/kg in male F344 and S-D rats, respectively) did not differ. Several studies have shown the importance of tissue repair on animal survival following exposure to toxic chemicals. The objective of this study was to investigate if differential rates of cell division and tissue repair might explain the lack of difference in LD50 dose between the two strains despite higher hepatotoxic injury in F344 rats. Age-matched male S-D and F344 rats were administered o-DCB (0.2, 0.6, 1.2 ml/kg, i.p.); injury and tissue repair occurring as two dynamic but opposing events were measured over time. Liver injury was assessed by measuring plasma alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities and by liver histopathology. Higher plasma ALT elevations were observed in F344 rats following administration of 0.2 and 0.6 ml o-DCB/kg. Using SDH as a marker of liver injury, the strain difference was evident only at 0.2 ml o-DCB/kg. Liver regeneration was estimated by 3H-thymidine incorporation into hepatonuclear DNA and via proliferating cell nuclear antigen (PCNA) assay. Prompt and significantly higher hepatocellular regeneration beginning at 36 h was evident in F344 rats following administration of 0.2 and 0.6 ml o-DCB/kg. The significantly higher depletion of hepatic glycogen observed in F344 rats following administration of 0.2 and 0.6 ml o-DCB/kg occurred without significant changes in plasma glucose and is consistent with highly stimulated tissue repair seen in these rats at the corresponding doses. However, increasing the dose further to 1.2 ml o-DCB/kg results in a delayed (S-phase synthesis begins at 48 h) and diminished response to o-DCB. These findings suggest that a significantly higher rate of tissue repair in F344 rats helps them overcome higher liver injury inflicted by o-DCB. This differential in tissue repair in the two strains may play a vital role in equalizing the ultimate outcome of toxicity in the two strains.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Archives of environmental contamination and toxicology 1 (1973), S. 36-47 
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract Oral administration of two isomeric tetrachlorobiphenyls (TCBs) (2, 3, 4, 5-and 3, 5, 3′, 5′-tetrachlorobiphenyls) to rats at three dosage levels does not cause any adverse effect on their growth. However, several hepatic enzyme systems are affected, even at the lowest level (5 mg/kg). EthylmorphineN-demethylase and aniline hydroxylase activities are slightly induced by 2, 3, 4, 5-TCB but, at a medium dose level (20 mg/kg), the activity ofpara-nitroanisoleO-demethylase is induced two-fold. Also, 3, 5, 3′, 5′-TCB induces these enzyme systems in male rats but decreases the activities of aniline hydroxylase and ethyl morphineN-demethylase in female rats at higher doses. An extra polar metabolite occurs in thein vitro metabolism of oestradiol-3H when female rats are treated with 2, 3, 4, 5-TCB at a dosage level of 40 mg/kg. UDP-Glucuronyl/transferase and δ-aminolevulinic acid synthetase activities are not affected by the administration of these two TCBs.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Archives of environmental contamination and toxicology 1 (1973), S. 245-254 
    ISSN: 1432-0703
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Abstract Mirex (dodecachlorooctahydro-1,3,4-metheno-2H-cyclobuta[cd]pentalene) was orally administered to male and female rats at daily dosages of 5, 10, 25, and 50 mg/kg for 5 days and its effects on aniline hydroxylas,p-nitroanisoleO-demethylase, ethyl morphine-N-demethylase, and UDP-glucruonyltransferase activities in the liver were studied. Liver-to-body weight ratios show significant increases at all of the doses tested, reaching maximum of 206 and 230 per cent of controls at a dose of 25 mg/kg for males and females, respectively. Metabolism of each of the substrates is altered by each dose of mirex fed. Aniline hydroxylase activity is decreased at all levels tested and the reduction is progressive with the dose. The Mirex content of rat liver microsomes is, by analysis, 9.69, 14.75, and 36.73 µg per 0.2gram-equivalents of liver microsomes from male rats treated at 10, 25, and 50 mg/kg, respectively. Aniline hydroxylase activity is not affected by addition of up to 400 µg of mirex to the reaction mixtures, using liver preparations from untreated animals.p-Nitroanisole demethylation activity is induced to a maximum in animals treated at 5 mg/kg. Ethyl morphine demethylase is induced to a maximum by 10 mg/kg in male and 25 mg/kg in female rats. Higher doses manifest a reversal ofp-nitroanisole-and ethyl morphine demethylase activities in both the sexes. Although the UDP-glucuronyl transferase specific activity is unaffected by mirex pretreatment, total activity in the liver increases to a maximum of 173 and 149 percent of controls at 25 mg/kg in males and females, respectively. Thus, it appears that chronic low doses of mirex seriously alter hepatic mixed-function oxidase systems of exposed animals, although mirex is not a substrate for any of these enzymes.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The carnitine, labelled with carbon-14 in the methyl groups, used in the present investigation was synthesized according to the method of Mazzetti et aZ.8, and the purity established by co-chromatography with authentic carnitine. The melting point of the synthesized material was 142 C. ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 69 (1995), S. 526-532 
    ISSN: 1432-0738
    Keywords: Key words Autoprotection ; Bled/recovered ; 2-Butoxyacetic acid ; 2-Butoxyethanol ; Ethylene glycol monobutyl ether ; Hematocrit ; Hematopoiesis ; Hematotoxicity ; Packed cell volume ; Pyrazole ; Red blood cells ; Resiliance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Pretreatment with a low dose of a toxic chemical protecting the animals from a subsequently administered lethal dose of the same chemical is called autoprotection. Autoprotection by model hepatotoxicants has been recently shown to be due to augmentation of cell division and tissue repair as well as an inherent resiliance of newly divided cells. The present studies were designed to investigate if an autoprotection model could be established in an extrahepatic tissue. The second objective was to test the hypothesis that inherent resiliance of newly divided cells is a major contributing mechanism for autoprotection. Female Sprague-Dawley rats (200–250 g) received a single administration of a moderately toxic but nonlethal dose (500 mg/kg, p.o.) 7 days prior to the administration of an LD90 dose (1500 mg/kg, p.o.) of the same compound. All rats receiving the initial protective dose are able to survive the lethal dose of butoxyethanol, in contrast to the death of those receiving the lethal dose alone. Following the administration of butoxyethanol, the hematocrit decreased from the normal 45% to 18% and by day 7, recovered to normal levels. Following the lethal challenge, hematocrit decreased to 13% in the naive rats, while decreasing only to 27% in rats receiving the protective dose, permitting animal survival. Administration of pyrazole to inhibit metabolism of butoxyethanol to butoxyacetic acid abolished autoprotection. A time-course study, wherein the time intervening between the protective and lethal dose of butoxyethanol was increased, indicated that 100% autoprotection observed at 7 days wanes to a mere 12%by day 21, suggesting that ageing of the newly formed cells results in loss of their resiliance to hemolysis. This was also confirmed by in vitro studies. To test the hypothesis that new blood cells that replace the hemolyzed cells form the basis of autoprotection, rats were bled and allowed to recover prior to challenge with a lethal dose of butoxyethanol. Bled/recovered rats demonstrated an 87% survival. In vitro incubation experiments revealed that the red blood cells from the bled/recovered rats were resilient to a 10-fold range of butoxyacetic acid concentration compared to cells from control rats. This work has led to the establishment of 2-butoxyethanol autoprotection model in an extrahepatic tissue. The mechanism of this autoprotection seems to be the inherent resiliance of newly formed red blood cells that replace the cells lost due to hemolysis caused by the protective dose.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Bulletin of environmental contamination and toxicology 8 (1972), S. 200-207 
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Notes: Summary About 58.5 percent of the uniformly labeled mirex-14C administered to rats as a single oral dose was excreted in feces and 0.69% in urine after 7 days. Considerable tissue storage of mirex was observed; fat, muscle, liver, kidneys and intestines contained 27.8, 3.20, 1.75, 0.76 and 0.23 percent of the total dose, respectively 7 days after treatment. While the first half-life of mirex was 38 hours, the projected second half-life was in excess of 100 days indicating a very slow rate of elimination from the body. No metabolite of mirex was detected in the feces, urine or any of the tissues. Nor was any mirex metabolite detected on incubation with rat, mouse, and rabbit liver preparations or plant root preparations. Mirex was concentrated by pea and bean roots and smaller amounts were translocated to the aerial parts when the plants were allowed to grow in water containing 1, 5 and 10 ppm mirex for 2 days. The resistance of mirex to biodegradation and its long biological half-life indicate that this insecticide may have an environmental half-life which far surpasses that of any previously studied insecticide.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0263-6484
    Keywords: Amiodarone neuropathy ; Na-, K-ATPase ; Mg2-ATPase ; rat brain synaptosomes ; p-nitrophenyl phosphatase ; ion transport in CNS ; ATP turnover in CNS ; ouabain binding ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Amiodarone hydrochloride is a diiodinated antiarrhythmic agent widely used in the treatment of cardiac disorders. With the increasing use of amiodarone, several untoward effects have been recognized and neuropathy following amiodarone therapy has recently been reported. The present studies were carried out to study the effect of amiodarone on rat brain synaptosomal ATPase in an effort to understand its mechanism of action. Na+, K+-ATPase and oligomycin sensitive Mg2+ ATPase activities were inhibited by amiodarone in a concentration dependent manner with IC50 values of 50 μM and 10 μM respectively. [3H]ouabain binding was also decreased in a concentration dependent manner with an IC50 value of 12 μM, and 50 μM amiodarone totally inhibited [3H]ouabain binding. Kinetics of [3H]ouabain binding studies revealed that amiodarone inhibition of [3H]ouabain binding is competitive. K+-activated p-nitrophenyl phosphatase activity showed a maximum inhibition of 32 per cent at 200 μM amiodarone. Synaptosomal ATPase activities did not show any change in rats treated with amiodarone (20mg kg-1 day-1) for 6 weeks, when compared to controls. The treatment period may be short, since the reported neurological abnormalities in patients were observed during 3-5 years of treatment. The present results suggest that amiodarone induced neuropathy may be due to its interference with sodium dependent phosphorylation of Na+, K+-ATPase reaction, thereby affecting active ion transport phenomenon and oxidative phosphorylation resulting in low turnover of ATP in the nervous system.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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