Pharmacology & toxicology最新文献_第6页

CYP1A1 but not CYP1A2 proteins are expressed in human lymphocytes. CYP1A1蛋白在人淋巴细胞中表达，而CYP1A2蛋白不表达。

Pharmacology & toxicology Pub Date : 2000-05-01 DOI: 10.1034/j.1600-0773.2000.d01-42.x

M Spatzenegger, Y Horsmans, R K Verbeeck

引用次数: 4

Myrica nagi attenuates cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in Swiss albino mice. 杨梅减轻异丙苯氢过氧化物诱导的瑞士白化病小鼠皮肤氧化应激和毒性。

Pharmacology & toxicology Pub Date : 2000-05-01 DOI: 10.1034/j.1600-0773.2000.d01-37.x

A Alam, M Iqbal, M Saleem, S Ahmed, S Sultana

{"title":"Myrica nagi attenuates cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in Swiss albino mice.","authors":"A Alam, M Iqbal, M Saleem, S Ahmed, S Sultana","doi":"10.1034/j.1600-0773.2000.d01-37.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-37.x","url":null,"abstract":"In recent years, considerable efforts have been made to identify new chemopreventive agents which could be useful for man. Myrica nagi, a subtropical shrub, has been shown to possess significant activity against hepatotoxicity and other pharmacological and physiological disorders. We have shown a chemopreventive effect of Myrica nagi on cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in mice. Cumene hydroperoxide treatment at a dose level of 30 mg/animal/0.2 ml acetone enhances susceptibility of cutaneous microsomal membrane for iron-ascorbate-induced lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and depletion in the level of cutaneous glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes such as glutathione S-transferase and quinone reductase has been observed. Application of Myrica nagi at doses of 2.0 mg and 4.0 mg/kg body weight in acetone prior to that of cumene hydroperoxide (30 mg/animal/0.2 ml acetone) treatment resulted in significant inhibition of cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in a dose-dependent manner. Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation induced by iron ascorbate and xanthine oxidase activities were significantly reduced (P<0.05). In addition the depleted level of glutathione, the inhibited activities of antioxidants, and phase II metabolizing enzymes were recovered to a significant level (P<0.05). The protective effect of Myrica nagi was dose-dependent. In summary our data suggest that Myrica nagi is an effective chemopreventive agent in skin and capable of ameliorating cumene hydroperoxide-induced cutaneous oxidative stress and toxicity.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 5","pages":"209-14"},"PeriodicalIF":0.0,"publicationDate":"2000-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21705650","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}

引用次数: 13

Bioavailability and pharmacokinetics of isradipine after oral and intravenous administration: half-life shorter than expected? 口服和静脉给药后isradipine的生物利用度和药代动力学:半衰期比预期短?

Pharmacology & toxicology Pub Date : 2000-04-01 DOI: 10.1034/j.1600-0773.2000.d01-32.x

H R Christensen, K Antonsen, K Simonsen, A Lindekaer, J Bonde, H R Angelo, J P Kampmann

{"title":"Bioavailability and pharmacokinetics of isradipine after oral and intravenous administration: half-life shorter than expected?","authors":"H R Christensen, K Antonsen, K Simonsen, A Lindekaer, J Bonde, H R Angelo, J P Kampmann","doi":"10.1034/j.1600-0773.2000.d01-32.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-32.x","url":null,"abstract":"Isradipine is a calcium channel-blocking agent of the dihydropyridine type, used in the treatment of hypertension. A terminal half-life of 8-9 hr has been reported, in several pharmacokinetic studies after oral administration of isradipine. In a yet unpublished study a much shorter half-life was observed, and the present trial was therefore conducted in order to estimate the half-life after intravenous administration of isradipine. The bioavailability was estimated as well. In a randomised cross-over design ten healthy young volunteers were given either isradipine orally or an intravenous infusion. The two study periods were separated by at least 3 days. Blood samples for measurement of isradipine concentration were collected for 10-12 hr after administration and half-life and bioavailability were estimated. Mean terminal half-life after intravenous administration was calculated to be 2.8 hr, and the bioavailability to be 0.28. None of the 10 subjects suffered from side effects. In the present intravenous study the half-life of isradipine seems to be of much shorter than demonstrated in previous oral studies.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 4","pages":"178-82"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21661498","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}

引用次数: 20

Protective effect of ebselen on aflatoxin B1-induced cytotoxicity in primary rat hepatocytes. 艾布selen对黄曲霉毒素b1诱导的大鼠原代肝细胞毒性的保护作用。

Pharmacology & toxicology Pub Date : 2000-04-01 DOI: 10.1034/j.1600-0773.2000.d01-29.x

C F Yang, J Liu, H M Shen, C N Ong

{"title":"Protective effect of ebselen on aflatoxin B1-induced cytotoxicity in primary rat hepatocytes.","authors":"C F Yang, J Liu, H M Shen, C N Ong","doi":"10.1034/j.1600-0773.2000.d01-29.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-29.x","url":null,"abstract":"Recent studies have shown that aflatoxin B1 enhances reactive oxygen species formation and causes oxidative damage, which may ultimately contribute to the cytotoxicity and carcinogenic effect of aflatoxin B1. Ebselen, 2-phenyl-1,2-benzoisoseleazol-3(H)-one, a synthetic seleno-organic compound has been shown to possess glutathione peroxidase-like activity and free radical scavenging ability. Thus present study was designed to investigate the protective effect of ebselen on aflatoxin B1-induced cytotoxicity in primary rat hepatocytes. Aflatoxin B1-induced cytotoxicity and lipid peroxidation were determined by lactate dehydrogenase leakage and malondialdehyde generation, respectively. Intracellular reactive oxygen species level was measured using the fluorescent probe 2',7'-dichlorofluorescin diacetate, and the intracellular reduced glutathione concentration was determined with a fluorometric method. Ebselen was found to display a dose-dependent protective effect on lactate dehydrogenase leakage and malondialdehyde generation caused by aflatoxin B1 exposure. The results also demonstrate that ebselen efficiently inhibits the intracellular reactive oxygen species formation in aflatoxin B1-treated hepatocytes in a dose and time-dependent manner. It was also noted that ebselen was able to increase the intracellular reduced glutathione concentration, both in the control and in aflatoxin B1-treated hepatocytes. The protection of ebselen against aflatoxin B1 cytotoxicity, however, was not affected by lowering the concentration of intracellular reduced glutathione. The overall data indicate that ebselen possesses a potent protective effect against aflatoxin B1-induced cytotoxicity, and the main mechanism involved in the protection may be its strong capability in inhibiting intracellular reactive oxygen species formation and preventing oxidative damage.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 4","pages":"156-61"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21660898","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}

引用次数: 24

The effect of aminophylline on right heart function in young pigs after ligation of the right coronary artery. 氨茶碱对猪右冠状动脉结扎术后右心功能的影响。

Pharmacology & toxicology Pub Date : 2000-04-01 DOI: 10.1034/j.1600-0773.2000.d01-34.x

M B Spalding, T I Ala-Kokko, K Kiviluoma, H Ruskoaho, S Alahuhta

引用次数: 8

Effect of nitric oxide synthase inhibitors on lipid peroxide formation in liver caused by endotoxin challenge. 一氧化氮合酶抑制剂对内毒素致肝脏脂质过氧化形成的影响。

Pharmacology & toxicology Pub Date : 2000-04-01 DOI: 10.1034/j.1600-0773.2000.d01-30.x

S Sakaguchi, S Furusawa, K Yokota, K Sasaki, M Takayanagi, Y Takayanagi

{"title":"Effect of nitric oxide synthase inhibitors on lipid peroxide formation in liver caused by endotoxin challenge.","authors":"S Sakaguchi, S Furusawa, K Yokota, K Sasaki, M Takayanagi, Y Takayanagi","doi":"10.1034/j.1600-0773.2000.d01-30.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-30.x","url":null,"abstract":"This study investigated the effect of nitric oxide on lipid peroxide formation during endotoxaemia. Nitric oxide synthase inhibitors N(G)-monomethyl-L-arginine acetate (L-NMMA, 20 mg/kg, intravenously), N(G)-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg, intravenously), and N(G)-nitro-L-arginine (L-NA, 10 mg/kg, intravenously), and a relatively selective inducible nitric oxide synthase inhibitor aminoguanidine (10 mg/kg, intravenously), did not protect against endotoxin-induced death of mice. Superoxide dismutase activity in liver 18 hr after administration of endotoxin (6 mg/kg, intraperitoneally) to L-arginine analogues (L-NMMA, L-NAME, L-NA)-treated mice was lower than in mice treated with endotoxin alone, whereas the administration of L-arginine analogues increased xanthine oxidase activity in the livers of endotoxin-injected mice compared with mice treated with endotoxin alone. In mice treated with L-arginine analogues and aminoguanidine, the levels of non-protein sulfhydryl and lipid peroxide in liver 18 hr after endotoxin injection did not show significant differences from mice treated with endotoxin alone. L-Arginine analogues and aminoguanidine had little effect on lipid peroxide formation in liver caused by endotoxin. Treatment with aminoguanidine (300 microM) significantly inhibited endotoxin-induced intracellular peroxide in J774A.1 cells, however, aminoguanidine did not affect endotoxin-induced cytotoxicity in J774A.1 cells. Our results clearly demonstrate that treatment with catalase (10 microg/ml), D-mannitol (10 mM), or superoxide dismutase (100 U/ml), has little or no effect on nitric oxide production by endotoxin (1 microg/ml)-activated J774A.1 cells. These findings suggest that nitric oxide is not crucial for lipid peroxide formation during endotoxaemia. Therefore, it is unlikely that nitric oxide plays a significant role in liver injury caused by free radical generation in endotoxaemia.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 4","pages":"162-8"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21661496","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}

引用次数: 11

Sensitivity to nitrogen mustard relates to the ability of processing DNA damage in Chinese hamster ovary cells. 对氮芥的敏感性与中国仓鼠卵巢细胞处理DNA损伤的能力有关。

Pharmacology & toxicology Pub Date : 2000-04-01 DOI: 10.1034/j.1600-0773.2000.d01-31.x

P Møller, K Wassermann, J Damgaard, B A Nexø, H Wallin

{"title":"Sensitivity to nitrogen mustard relates to the ability of processing DNA damage in Chinese hamster ovary cells.","authors":"P Møller, K Wassermann, J Damgaard, B A Nexø, H Wallin","doi":"10.1034/j.1600-0773.2000.d01-31.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-31.x","url":null,"abstract":"The hallmark of the excision repair pathways is the removal of DNA adducts by excision of the damaged nucleotides. In the course of repair, transient DNA strand breaks occur, which can be measured by the Comet assay. We have investigated the processing of DNA damage, mediated by nitrogen mustard, in wild-type AA8 Chinese hamster ovary cells, and in UV5, UV20 and UV41 DNA repair deficient cell lines. Whereas DNA repair could not be detected by unscheduled DNA synthesis at nitrogen mustard doses below 10 microM, processing of nitrogen mustard-mediated DNA damage was observed by the Comet assay at a 100-times lower concentration. Wild-type Chinese hamster ovary AA8 cells were able to process nitrogen mustard-mediated DNA damage within 4-24 hr depending on the dose of nitrogen mustard (0.1-10 microM). None of the repair-deficient cell lines was able to completely process the DNA damage induced by 10 microM nitrogen mustard. At nitrogen mustard doses that conferred 10% colony forming ability, the repair-deficient cells had an altered processing of nitrogen mustard-mediated DNA damage: In the AA8, UV20, and UV41 cells, the amplitude of strand breaks peaked early (within 4 hr), the level of strand breaks in the nitrogen mustard exposed UV20 and UV41 cells did not return to the baseline of the unexposed reference culture, and the peak in strand breaks in the UV5 cell line occurred after 4 hr. Our results indicate that the single cell gel electrophoresis (Comet) assay is suitable for assessing repair capability of DNA alkylations.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 4","pages":"169-77"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21661497","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}

引用次数: 9

Influence of ageing on vasomotor responses of human epicardial coronary arteries. 衰老对人心外膜冠状动脉血管舒缩反应的影响。

Pharmacology & toxicology Pub Date : 2000-04-01 DOI: 10.1034/j.1600-0773.2000.d01-33.x

O Saetrum Opgaard, H T Ytterberg, P R Saxena, L Edvinsson

{"title":"Influence of ageing on vasomotor responses of human epicardial coronary arteries.","authors":"O Saetrum Opgaard, H T Ytterberg, P R Saxena, L Edvinsson","doi":"10.1034/j.1600-0773.2000.d01-33.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-33.x","url":null,"abstract":"Vasomotor responses to various agonists were studied on isolated circular segments of human epicardial coronary arteries from three different age groups; 23-38 years, 40-58 years and 63-86 years. Noradrenaline had no or only weak contractile effect on coronary arteries from younger patients but induced contraction of all artery segments from older patients. The Emax value was significantly (P<0.0001) higher in arteries from the oldest group compared to each of the two younger age groups, whereas the potency was similar in all three groups. Linear regression analysis of noradrenaline-induced contraction in individual patients revealed a significantly positive age-correlation (correlation coefficient 0.67, P<0.0001). Contraction induced by endothelin-1 and relaxation induced by substance P, calcitonin gene-related peptide and vasoactive intestinal peptide on arteries precontracted with U46619 showed no significant differences in maximum responses and potencies between the three age groups, and no significant linear age-correlation. These data demonstrate a large variability in contractile responses to noradrenaline with contractions seen mostly in coronary arteries from older patients. It thus seems that sympathetic activation could contribute to coronary ischaemia in some patients.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 4","pages":"183-91"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21661499","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}

引用次数: 8

Neurotoxic effects of three fractions isolated from Tityus serrulatus scorpion venom. 三种蝎毒分离物的神经毒性作用。

Pharmacology & toxicology Pub Date : 2000-04-01 DOI: 10.1034/j.1600-0773.2000.d01-28.x

A L Nencioni, F F Carvalho, I Lebrun, V A Dorce, M R Sandoval

{"title":"Neurotoxic effects of three fractions isolated from Tityus serrulatus scorpion venom.","authors":"A L Nencioni, F F Carvalho, I Lebrun, V A Dorce, M R Sandoval","doi":"10.1034/j.1600-0773.2000.d01-28.x","DOIUrl":"https://doi.org/10.1034/j.1600-0773.2000.d01-28.x","url":null,"abstract":"Scorpion venoms contain low molecular weight basic polypeptides, neurotoxins, that are the principal toxic agents. These toxins act on ion channels, promoting a derangement that may result in an abnormal release of neurotransmitters. In the present study we investigated some of the effects of the F, H and J fractions isolated from Tityus serrulatus scorpion venom on the central nervous system of rodents. The venom was partially purified by gel filtration chromatography. The neurotoxic effect of these fractions was studied on convulsive activity after intravenous injection, and on electrographic activity and neuronal integrity of rat hippocampus when injected directly into this brain area. The results showed that intravenous injection of the F and H fractions induced convulsions, and intrahippocampal injection caused electrographic seizures in rats and neuronal damage in specific hippocampal areas. Fraction J injected intravenously reduced the general activity of mice in the open field but induced no changes when injected into the brain. These results suggest that scorpion toxins are able to act directly on the central nervous system promoting behavioural, electrographic and histological modifications.","PeriodicalId":19876,"journal":{"name":"Pharmacology & toxicology","volume":"86 4","pages":"149-55"},"PeriodicalIF":0.0,"publicationDate":"2000-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21661614","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}

引用次数: 0

The preservatives ethyl-, propyl- and butylparaben are oestrogenic in an in vivo fish assay. 防腐剂乙基，丙基和对羟基苯甲酸丁酯是雌激素在体内鱼试验。

Pharmacology & toxicology Pub Date : 2000-03-01 DOI: 10.1034/j.1600-0773.2000.d01-20.x

K L Pedersen, S N Pedersen, L B Christiansen, B Korsgaard, P Bjerregaard

引用次数: 56