ALTERED LIPID METABOLISM IN PEROXISOMAL PROLIFERATION
ALTERED LIPID METABOLISM IN PEROXISOMAL PROLIFERATION
批准号:
3438148
负责人:
MOSTAFA Zaki BADR
金额:
$7.08万
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-05-01 至 1990-10-31
关键词:
chemical structure function clofibrate diethylhexylphthalate environmental toxicology enzyme mechanism fatty acid metabolism gender difference guinea pigs hamsters histology ketones laboratory rat lipid metabolism liver metabolism liver pharmacology microscopy nicotinate peroxisome physical chemical interaction
中文摘要
邻苯二甲酸酯,广泛分散的增塑剂
环境,以及几种临床使用的降高脂血症
药物,诱导过氧化物体,并已被牵连到
肝细胞癌。这些生物的机制
目前还没有明确的回应。然而,2-乙基己醇是一种主要的
常用增塑剂邻苯二甲酸二乙基己酯的代谢物,
抑制灌流肝脏中肝酮的生成。2-
乙基己醇还导致循环酮小体减少。
伴随着微泡脂质的快速积累
仅在活体肝小叶的门脉周围区域。
因此,本文件中概述的实验的目的
应用是评估过氧酶体的假说
增殖物最初抑制酮的生成并导致脂质
在肝脏中积聚。血脂的增加可能是一种常见的
导致对这些化合物的生物反应的影响。至
检验这一假设,我们将研究脂肪酸的变化
多种过氧化物体增殖物在人体内的代谢
肝脏灌流和活体内对不同反应的物种
增殖物(大鼠、仓鼠、豚鼠)。信息来自
这些研究最终将导致阐明
过氧化体增殖物诱导其毒性的机制(S)
生物效应,并因此可能提供一种合理的手段
以防止它们的毒性。
英文摘要
Phthalic acid esters, widely dispersed plasticizers in the
environment, as well as several clinically used antihyperlipidemic
drugs, induce peroxisomes and have been implicated in
hepatocellular carcinoma. Mechanisms for these biological
responses are not clear. However, 2-ethylhexanol, a primary
metabolite of the common plasticizer diethylhexyl phthalate,
inhibited hepatic ketogenesis in the perfused liver. 2-
ethylhexanol also caused circulating ketone bodies to decline
concomitantly with a rapid accumulation of microvesicular lipid
exclusively in periportal regions of the liver lobule in vivo.
Therefore, the purpose of the experiments outlined in this
application is to evaluate the hypothesis that peroxisomal
proliferators initially inhibit ketogenesis and cause lipid to
accumulate in the liver. Increases in lipid may be a common
effect leading to the biological response to these compounds. To
test this hypothesis, we will study changes in fatty acid
metabolism due to a variety of peroxisomal proliferators in
perfused livers and in vivo in species with different responses to
proliferators (rats, hamsters, guinea pigs). Information from
these studies will lead ultimately to the elucidation of
mechanism(s) by which peroxisomal proliferators elicit their toxic
biological effects and may consequently, provide a rational means
to prevent their toxicity.
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Induction of peroxisomal enzyme activities by di-(2-ethylhexyl) phthalate in thyroidectomized rats with parathyroid replants.
邻苯二甲酸二(2-乙基己基)酯诱导甲状腺切除大鼠甲状旁腺再植的过氧化物酶体酶活性。
DOI:
--
发表时间:
1992
期刊:
The Journal of pharmacology and experimental therapeutics
影响因子:
--
作者:
[Badr,MZ]
通讯作者:
Badr,MZ
Regulation of perfluorooctanoic acid--induced peroxisomal enzyme activities and hepatocellular growth by adrenal hormones.
肾上腺激素对全氟辛酸诱导的过氧化物酶体酶活性和肝细胞生长的调节。
DOI:
10.1002/hep.1840150223
发表时间:
1992
期刊:
Hepatology (Baltimore, Md.)
影响因子:
--
作者:
[Thottassery,J, Winberg,L, Youssef,J, Cunningham,M, Badr,M]
通讯作者:
Badr,M
Mechanism of phthalate-induced inhibition of hepatic mitochondrial beta-oxidation.
邻苯二甲酸盐诱导的肝线粒体β-氧化抑制机制。
DOI:
10.1016/0378-4274(94)03199-1
发表时间:
1995
期刊:
Toxicology letters
影响因子:
3.5
作者:
[Winberg,LD, Badr,MZ]
通讯作者:
Badr,MZ
Mechanism of aluminum-induced inhibition of hepatic glycolysis: inactivation of phosphofructokinase.
DOI:
--
发表时间:
1990-07
期刊:
The Journal of pharmacology and experimental therapeutics
影响因子:
--
作者:
[Zhi-Xin Xu;L. Fox;S. Melethil;L. Winberg;M. Badr]
通讯作者:
Zhi-Xin Xu;L. Fox;S. Melethil;L. Winberg;M. Badr
BRAIN OXIDATIVE STRESS--A SIGN OF AGING OR EMINENT DEATH
-
批准号:6195289
-
项目类别:
-
资助金额:$7.25万
-
财政年份:2000
-
负责人:MOSTAFA Zaki BADR
-
依托单位:
AGING PPAR AND HEPATIC PEROXISOMES
-
批准号:2012369
-
项目类别:
-
资助金额:$9.96万
-
财政年份:1997
-
负责人:MOSTAFA Zaki BADR
-
依托单位:
海外基金