Journal of biochemical toxicology最新文献

{"title":"A phase model for the gas–liquid equilibria in the ammonia–carbon dioxide–water–urea system in chemical equilibrium at urea synthesis conditions. II. Experimental verification","authors":"S. Lemkowitz, Eric Vet, P. Berg","doi":"10.1002/JBT.2570270149","DOIUrl":"https://doi.org/10.1002/JBT.2570270149","url":null,"abstract":"Bubble- and critical-points in the ammonia–carbon dioxide plane and ammonia–urea system are presented as well as bubble-points in the carbon dioxide–urea system. In order to confirm the form of a previously presented phase model a large number of bubble- and dew-points were measured at various ammonia–carbon dioxide–water–urea compositions (including those most important to the urea industry) in the range of 140 ⩽ T ⩽ 200°C and 15 < P < 400 atm. All of the measurements were carried out under conditions of complete chemical equilibrium. The results are in agreement with the ternary phase model presented in a previous article.","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"82 1","pages":"335-348"},"PeriodicalIF":0.0,"publicationDate":"2007-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79326462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative damage and antioxidant status in the lungs and bronchoalveolar lavage fluid of rats exposed chronically to cigarette smoke.","authors":"H Wurzel, C C Yeh, C Gairola, C K Chow","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effect of chronic smoke exposure on oxidative damage and antioxidant status was studied in rats. Ten-week-old female Sprague-Dawley rats were exposed to fresh mainstream cigarette smoke or filtered room air twice daily, or maintained as room controls, for 65 weeks. Animals were sacrificed 18-20 hours after the last treatment. The bronchoalveolar lavage (BAL) fluid, lung tissues, and plasma were processed to assess oxidative damage and antioxidant status. Compared with sham and room control groups, the levels of conjugated dienes and alpha-tocopheryl quinone were significantly higher in the lung tissues of rats exposed to cigarette smoke. The levels of malondialdehyde, protein carbonyls, reduced glutathione (GSH), ascorbic acid and vitamin E, and activities of catalase and GSH peroxidase in the lung tissues were not significantly altered by smoke exposure. No significant differences in any measurements were found in BAL fluid and plasma among the experimental groups. The results obtained support the view that cigarette smoking increases oxidative stress and suggest a metabolic adaptation of antioxidant systems following chronic smoke exposure.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"10 1","pages":"11-7"},"PeriodicalIF":0.0,"publicationDate":"1995-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18602870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible mechanism of adenosine protection in carbon tetrachloride acute hepatotoxicity. Role of adenosine by-products and glutathione peroxidase.","authors":"V Chagoya de Sánchez,&nbsp;R Hernández-Muñoz,&nbsp;L Yáñez,&nbsp;S Vidrio,&nbsp;M Díaz-Muñoz","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Adenosine proved to be an effective hepatoprotector increasing the survival rate of rats receiving lethal doses of CCl4. Searching for the mechanism of action, we found that adenosine transiently prevents the necrotic liver damage associated to an acute CCl4 treatment. The antilipoperoxidative action of the nucleoside was evidenced by a decrease of TBA-reactive products and the diene conjugates elicited by the hepatotoxin. Adenosine's protective effect was demonstrated by reverting the decrease of cytochrome P-450 while preserved intact the activity of the microsomal enzyme glucose-6-phosphatase. CCl4 promoted an increase in the oxidant stress through an enhancement in oxidized glutathione levels. This action was also completely counteracted by the nucleoside. Adenosine was unable to prevent CCl4 activation and, even, increased .CCl3 formation in the presence of PBN in vivo. However, in the presence of the nucleoside, irreversible binding of 14CCl4 to the microsomal lipid fraction of the treated animals was decreased. These results suggest that adenosine protective action might be exerted at the level of the propagation reaction following CCl4 activation. Two possible mechanisms were associated to the nucleoside protection: (1) the peroxide-metabolyzed enzymes, GSH-per, showed a marked increase after 30 minutes of adenosine treatment, which was potentiated by the hepatotoxin, suggesting an important role of this enzyme in the nucleoside's action; (2) the adenosine catabolism induced an increase in uric acid level, and allopurinol, a purine metabolism inhibitor, prevented such elevation as well as the antilipoperoxidative action of adenosine and the increase of GSH-per associated with the nucleoside treatment. These facts strongly suggest that the protective effect elicited by adenosine is not a direct one, but rather is related to its catabolic products, such as uric acid, which has been recognized as a free radical scavenger.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"10 1","pages":"41-50"},"PeriodicalIF":0.0,"publicationDate":"1995-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18600857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo temperature modulation of hepatic metabolism and DNA adduction of aflatoxin B1 in rainbow trout.","authors":"H M Carpenter,&nbsp;Q Zhang,&nbsp;C el Zahr,&nbsp;D P Selivonchick,&nbsp;D E Brock,&nbsp;L R Curtis","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alterations in membrane lipid composition during temperature acclimation of poikilotherms is hypothesized to compensate for direct effects of temperature on membrane fluidity. Temperature also influences disposition and actions of some xenobiotics. This suggests the potential for complex interactions between temperature and metabolism of chemical carcinogens. Whole livers and hepatic microsomes from rainbow trout acclimated at 18 degrees C have more saturated fatty acids and less mono- and polyunsaturated fatty acids than those from fish acclimated at 10 degrees C. Such changes are consistent with a role for membrane lipid fluidity in temperature compensation. When 10 and 18 degrees C acclimated fish are ip injected with 0.4 mg/kg [3H]aflatoxin B1 (AFB1) at their respective acclimation temperatures, hepatic disposition of AFB1, DNA adduction, and biliary metabolites are similar. An acute shift of 18 degrees C acclimated trout to 14 degrees C reduces [3H]AFB-DNA adduct formation, while [3H]AFB1 adduction after acute shift of 10 degrees C acclimated fish to 14 degrees C is no different than in non-shifted fish. Hepatic microsomes isolated from 10 or 18 degrees C acclimated trout, incubated with 10 microM [3H]AFB1 and calf thymus DNA between 6 and 22 degrees C exhibit no differences in the \"break points\" of Arrhenius plots (16 degrees C in both groups). There is, however, more in vitro DNA adduction of [3H]AFB1 by microsomes from 18 degrees C acclimated fish, a difference abolished by 0.5 mM alpha-naphthoflavone (ANF). These results suggest that temperature acclimation of trout differentially modifies activities of cytochrome P-450 isozymes. When assayed at respective acclimation temperatures, hepatic cytosol from 18 degrees C fish produces more aflatoxicol, a detoxication product of AFB1, than cytosol from 10 degree C fish. Therefore, this soluble enzyme does not exhibit ideal temperature compensation. Such temperature-induced differences in microsomal cytochrome P-450 isozymes and cytosolic dehydrogenase partially explain temperature-modulated AFB1 genotoxicity.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"10 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"1995-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18602869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of natural polyphenols on aflatoxin B1 activation in a reconstituted microsomal monooxygenase system.","authors":"P F Firozi,&nbsp;R K Bhattacharya","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Covalent adduct formation between aflatoxin B1 and DNA, as catalyzed by a reconstituted microsomal monooxygenase system containing purified cytochrome P450 and NADPH-cytochrome P450 reductase, was observed to be inhibited by certain polyphenolic compounds of natural origin. Polyhydroxylated flavonoids were found to be more effective than phenolic acids and displayed dose-dependent inhibition. The inhibition (50%) could be reversed by increasing the amount of cytochrome P450 but not by increasing the amount of reductase. Each polyphenol inhibited NADPH-cytochrome P450 reductase activity as measured by reduction of cytochrome C. This inhibition could be reversed with higher amounts of cytochrome C. This inhibition, however, could not be reversed if an artificial electron acceptor, dichlorophenolindophenol, was used in place of cytochrome C. These results suggest a strong affinity of polyphenols toward cytochromes. This conclusion was further supported from the observation that pretreatment of cytochrome P450 with each polyphenol reduced its ability to catalyze aflatoxin B1-DNA adduct formation in the reconstituted system. Natural polyphenols, thus, may have the ability to modulate chemical carcinogenesis by modulating cytochrome P450 function.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"10 1","pages":"25-31"},"PeriodicalIF":0.0,"publicationDate":"1995-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18600855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity of some nuclear enzymes associated with DNA repair following hepatocarcinogen administration to rats.","authors":"R P Webster,&nbsp;R K Bhattacharya","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Administration of hepatocarcinogens aflataxin B1 (AFB1) and N-nitrosodimethylamine (NDMA) to rats caused single-strand breaks in hepatic nuclear DNA. The damage was found to be maximum at 4 hours following AFB1 administration and at 2 hours following NDMA administration. These damages were repaired after 17 and 4 hours, respectively in cases of AFB1 and NDMA. The activity of poly(ADP-ribose)polymerase (PARP), an enzyme known to use single-strand breaks of DNA as cofactor, was observed to increase with increasing damage to DNA and decrease as and when this damage got repaired. DNA polymerase beta and DNA ligase activities were also seen to increase and decline in a way analogous to PARP. In contrast, DNA topoisomerase activity declined corresponding to an increase in PARP activity. These observations suggest a possible role of PARP in coordinating the activities of other enzymes involved in DNA repair. It is also envisaged that these parameters can be utilized to devise strategies to counteract the deleterious effects of chemical carcinogens.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"10 1","pages":"33-40"},"PeriodicalIF":0.0,"publicationDate":"1995-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18600856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations of histone phosphorylation in rat spleen cells after treatment with the aromatic amine, 4,4'-methylene-bis(2-chloroaniline).","authors":"D G DeBord,&nbsp;K L Cheever,&nbsp;A D Booth-Jones,&nbsp;T F Swearengin,&nbsp;R E Savage","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alterations of the phosphorylation pattern of histones by the carcinogen, 4,4'-methylene-bis(2-chloroaniline) (MOCA) were investigated using rodent spleen cells. Spleen cells were isolated from Sprague-Dawley rats and treated with either 5, 10, 25, or 50 microM MOCA or acetone vehicle controls for 1, 2, 4, or 8 hours. Cells were incubated with 32P-phosphoric acid, and histones from these cells were fractionated utilizing two-dimensional polyacrylamide gel electrophoresis. Marked stimulation of histone phosphorylation was observed with the 10 microM MOCA treatment. A transient decrease in histone phosphorylation was observed at the 1 and 2 hour time points followed by a marked stimulation at 4 hours.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"10 1","pages":"19-23"},"PeriodicalIF":0.0,"publicationDate":"1995-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18600854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of the hepatic CYP2B and CYP3A enzymes by the proestrogenic pesticide methoxychlor and by DDT in the rat. Effects on methoxychlor metabolism.","authors":"H C Li,&nbsp;S S Dehal,&nbsp;D Kupfer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In earlier investigations, methoxychlor treatment did not elicit induction of hepatic P450 monooxygenases in rats, apparently due to the short half-life of methoxychlor in vivo. The current study demonstrates that multiple bidaily doses of methoxychlor to female rats produce a marked induction of the hepatic microsomal P450 2B1/2B2 and 3A proteins. There was no increase in CYP1A1 or CYP2E1 proteins, demonstrating selectivity of induction by methoxychlor. Similarly, treatment with DDT, a methoxychlor analog, increased CYP2B and 3A proteins but had no effect on CYP1A1 and 2E1. Methoxychlor moderately elevated the enzymatic activity corresponding to CYP2B and 3A catalysis. In immature rats, only the higher dose of methoxychlor (300 mg/kg), produced elevation of testosterone hydroxylation at the 16 alpha position (major product) that was statistically significant, indicative of increased catalysis by CYP2B1/2B2. Both the low (150 mg/kg) and high dose (300 mg/kg) of methoxychlor increased the 6 beta hydroxylation (major product) and 2 beta and 15 beta hydroxylation (minor products) of testosterone, indicative of increased catalysis by CYP3A. In mature female rats, both methoxychlor and DDT treatment elevated the 16 alpha and 6 beta hydroxylation and androstenedione formation. Additional indication of methoxychlor- and DDT-mediated induction of CYP2B enzymatic activity in mature and immature rats was evident from increased ring hydroxylation of methoxychlor, an activity attributed to CYP2B. These findings indicate that methoxychlor and DDT belong to the phenobarbital type of inducers and that exposure to methoxychlor can affect its own metabolism. The methoxychlor-mediated increase in CYP2B and 3A proteins was considerably larger than the increase in the corresponding enzymatic activities. The possible reasons for the lack of correlation between P450 levels and their enzymatic activities and the potential relevance of induction by methoxychlor to its metabolism and toxicity are discussed.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"10 1","pages":"51-61"},"PeriodicalIF":0.0,"publicationDate":"1995-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18600858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significance of mirex-caused hypoglycemia and hyperlipidemia in rats.","authors":"L Jovanovich,&nbsp;S Levin,&nbsp;M A Khan","doi":"10.1002/jbt.2570020305","DOIUrl":"https://doi.org/10.1002/jbt.2570020305","url":null,"abstract":"<p><p>Treatment of rats with mirex (40 ppm in diet) caused hypoglycemia, liver enlargement, and inhibition of adrenal corticosteroid-synthesizing enzyme activity. At toxic dosages (20,000 ppm mirex in diet, which has a lethal toxicity-50 [LT-50] of ten days) poisoned female rats showed severe hypoglycemia, fatty liver, adrenal hyperplasia, hypophagia, lipid mobilization, and body weight (bw) loss. A 50 micrograms/kg intraperitoneal (IP) dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in male rats caused similar effects two days posttreatment. Hypoglycemia could be overcome by prednisone (which also inhibited adrenocorticoid-synthesizing enzyme activities) but not by streptozotocin treatment, indicating that hypoglycemia may be related to glucocorticoid deficiency resulting from inhibition of their synthesis and not by direct effects on pancreatic beta-cells. Glucocorticoid deficiency could also cause increased release of adrenocorticoid hormone (ACTH), which may enhance fat mobilization caused by hypophagia.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"203-13"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14630644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of cellular calcium homeostasis in toxic liver injury induced by the pyrrolizidine alkaloid senecionine and the alkenal trans-4-OH-2-hexenal.","authors":"D S Griffin,&nbsp;H J Segall","doi":"10.1002/jbt.2570020302","DOIUrl":"https://doi.org/10.1002/jbt.2570020302","url":null,"abstract":"<p><p>The pyrrolizidine alkaloid senecionine has been shown to be hepatotoxic, genotoxic, and cytotoxic. However, the biochemical mechanism by which senecionine produces hepatocellular toxicity remains to be elucidated. The role of calcium homeostasis in toxic liver injury was examined in isolated rat hepatocytes treated with senecionine and trans-4-OH-2-hexenal (t-4HH), a microsomal metabolite of senecionine, and appropriate cofactors. Hepatocytes treated with senecionine and t-4HH demonstrated greater cytotoxicity (leakage of lactate dehydrogenase) when incubated in the absence of extracellular Ca2+ than in its presence. Both compounds elicited an increase in cytosolic Ca2+ levels of isolated hepatocytes in the presence of extracellular Ca2+. In the following study, senecionine and t-4HH depleted intracellular glutathione levels and induced lipid peroxidation and cytotoxicity in isolated hepatocytes. Pretreatment with the thiol-group reducing agent dithiothreitol prevented depletion of intracellular glutathione and protected hepatocytes against senecionine and t-4HH-induced lipid peroxidation and cytotoxicity. Both compounds also depleted intracellular ATP and NADPH levels. These results suggest that hepatotoxicity induced by senecionine and t-4HH is not dependent on the influx of extracellular Ca2+; however, alterations in intracellular Ca2+, possibly associated with depletion of intracellular glutathione, NADPH, and ATP, may play a critical role.</p>","PeriodicalId":15255,"journal":{"name":"Journal of biochemical toxicology","volume":"2 ","pages":"155-67"},"PeriodicalIF":0.0,"publicationDate":"1987-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jbt.2570020302","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14630645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}