Research communications in chemical pathology and pharmacology最新文献_第6页

Developmental toxicity of cyclohexanediaminetetraacetic acid (CDTA) in mice. 环己二胺四乙酸(CDTA)对小鼠的发育毒性。

Research communications in chemical pathology and pharmacology Pub Date : 1994-03-01

D J Sánchez, M T Colomina, J L Domingo, J M Llobet, J Corbella

{"title":"Developmental toxicity of cyclohexanediaminetetraacetic acid (CDTA) in mice.","authors":"D J Sánchez, M T Colomina, J L Domingo, J M Llobet, J Corbella","doi":"","DOIUrl":"","url":null,"abstract":"Cyclohexanediaminetetraacetic acid (CDTA), an effective antagonist for the treatment of zinc, lead, and manganese poisoning was evaluated for maternal and developmental toxicity in pregnant Swiss mice. CDTA was given intraperitoneally on gestation days 6-15 at doses of 0, 270, 540, and 1080 mg/kg/day. On gestational day 18, the fetuses were examined for external, visceral, and skeletal malformations and variations. Treatment with CDTA at 1080 mg/kg/day resulted in a high level of maternal deaths, as well as less severe clinical signs (significant reduction in weight gain and food consumption). Increased resorptions, fetal deaths, and decreased number of live fetuses per litter were observed at 1080 mg/kg/day. Mean fetal body weights were also significantly decreased in this group. At 1080 mg/kg/day, CDTA caused external malformations, while the development of skeletal tissues was less affected. The no observable adverse effect level (NOAEL) for maternal and developmental toxicity of CDTA in mice was 540 mg/kg/day. Analyses of maternal and fetal tissues revealed only slight effects of CDTA on concentrations of calcium, magnesium, zinc, copper and iron. According to these results, the alterations in mineral metabolism should not be the major reason for CDTA-induced developmental toxicity.","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"83 3","pages":"329-40"},"PeriodicalIF":0.0,"publicationDate":"1994-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19001923","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

Characterization of and the influence of calcium channel blockers on the renal excretion of pyrimidine anticancer agents. 钙通道阻滞剂的特性及对嘧啶类抗癌药物肾排泄的影响。

Research communications in chemical pathology and pharmacology Pub Date : 1994-03-01

M A Enigbokan, J Preston, C Hubbard, J O Thompson

{"title":"Characterization of and the influence of calcium channel blockers on the renal excretion of pyrimidine anticancer agents.","authors":"M A Enigbokan, J Preston, C Hubbard, J O Thompson","doi":"","DOIUrl":"","url":null,"abstract":"The renal handling of two anticancer (a-Ca) pyrimidines 5-fluorodeoxyuridine (FUdR) and 5-fluorouracil (5-FU) was investigated in clearance experiments in CF-1 mice using specific inhibitors of classical renal transport systems. The 5-FU was derived from the metabolism of FUdR. Based on the FUdR:inulin clearance ratio and 5-FU:inulin clearance ratio, it was determined that FUdR was secreted into renal tubules while 5-FU underwent reabsorption. The secretion of FUdR was inhibited by cimetidine and dipyridamole but not by probenecid or phloridzin. While the clearance ratio of 5-FU:inulin was significantly reduced by phloridzin, it (i.e., the ratio) was not affected by cimetidine, dipyridamole, or probenecid. The impact of two calcium channel blockers, diltiazem (DZM) and verapamil (VER), on the renal handling of FUdR and 5-FU was also examined. VER increased the secretion of FUdR without affecting the reabsorption of 5-FU while DZM slightly decreased the secretion of FUdR and prevented the reabsorption of 5-FU. These data suggest that the organic cation carrier and a dipyridamole-sensitive nucleoside transporter are involved in the renal excretion of FUdR; that the renal transport of both FUdR and 5-FU is associated with the calcium channel; and that 5-FU utilizes, at least in part, the glucose transporter for its reabsorption.","PeriodicalId":21140,"journal":{"name":"Research communications in chemical pathology and pharmacology","volume":"83 3","pages":"270-8"},"PeriodicalIF":0.0,"publicationDate":"1994-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19003623","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

Tetrazole isosteres of biologically active acids and their effects on enzymes. 生物活性酸的四唑异构体及其对酶的影响。