Hypolipidemic Agents

Bencze, W. L.; Hess, R.; deStevens, George

doi:10.1007/978-3-0348-7068-9_5

Cited by 10 publications

(8 citation statements)

References 250 publications

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“…Non-hydroxylated triphenylethylenic antiestrogens, 6-or 7-ketosterols were inhibitors of D8D7I whereas hydroxylated antiestrogens were inhibitors of DHCR24. The presence of one (4-OH-tamoxifen) or two hydroxyl groups within the hydrophobic backbone (RU 39,411 and raloxifene) seems to be associated with the inhibition of DHCR24 because triparanol and ethamoxytriphetol are known inhibitors of DHCR24 (31,48). Raloxifene is the only phenolic antiestrogen compound of our series that is also an inhibitor of D8D7I.…”

Section: Fig 7 Inhibition Of [mentioning

confidence: 99%

Molecular Characterization of the Microsomal Tamoxifen Binding Site

Kedjouar

Médina

Oulad-Abdelghani

et al. 2004

Journal of Biological Chemistry

108

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Tamoxifen is a selective estrogen receptor modulator widely used for the prophylactic treatment of breast cancer. In addition to the estrogen receptor (ER), tamoxifen binds with high affinity to the microsomal antiestrogen binding site (AEBS), which is involved in ERindependent effects of tamoxifen. In the present study, we investigate the modulation of the biosynthesis of cholesterol in tumor cell lines by AEBS ligands. As a consequence of the treatment with the antitumoral drugs tamoxifen or PBPE, a selective AEBS ligand, we show that tumor cells produced a significant concentration-and time-dependent accumulation of cholesterol precursors. Sterols have been purified by HPLC and gas chromatography, and their chemical structures determined by mass spectrometric analysis. The major metabolites identified were 5␣-cholest-8-en-3␤-ol for tamoxifen treatment and 5␣-cholest-8-en-3␤-ol and cholesta-5,7-dien-3␤-ol, for PBPE treatment, suggesting that these AEBS ligands affect at least two enzymatic steps: the 3␤-hydroxysterol-⌬ Tamoxifen is a selective estrogen receptor modulator (SERM) widely used for the treatment and the prevention of breast cancer (1). More than 20 years ago, Sutherland et al. (2) discovered that tamoxifen bound to a high affinity binding site that was different from the estrogen receptor (2). This site has been named the microsomal antiestrogen binding site (AEBS) 1 because it is localized in the microsomes of cells; it binds principally aryl aminoethoxy antiestrogens and has no affinity for estrogens (3). Two classes of selective ligands have been developed so far to selectively target the AEBS. The first class includes diphenylmethane derivatives of tamoxifen (DPPE) and N-pyrrolidino-2-[4-(benzyl)-phenoxy-ethanamine⅐HCl (PBPE) (4 -6), while the second class includes oxygenated derivatives of cholesterol such as 7-ketocholestanol (7-9). We and others (5, 10 -14) have shown that AEBS ligands inhibit the growth of tumor cell lines in vitro and in vivo, demonstrating that the AEBS was involved in the mediation of the effects of these structural classes of its cognate ligands. These compounds represent not only specific tools to study AEBS function but are also anticancer drug candidates because the selective AEBS ligand DPPE (Tesmilifene) was brought up to phase II and III clinical trials for the treatment of breast and prostate cancer in association with doxorubicin (15-17). Two principal points remained unsolved: the first is the precise molecular nature of the AEBS and the second the explanation of the difference observed between the nanomolar affinity of AEBS ligands and their micromolar effectiveness for growth control and cytotoxicity.We have been involved in the identification of the AEBS for several years. The AEBS can be found in most tissues in mammals and is abundant in microsomes of liver that contained 20 -30ϫ the amount found in tumor cell lines (18). For this reason, the liver have been chosen for the purification of the AEBS but the pharmacological profiles of the AEBS found in the ...

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Section: Fig 7 Inhibition Of [mentioning

confidence: 99%

Molecular Characterization of the Microsomal Tamoxifen Binding Site

Kedjouar

Médina

Oulad-Abdelghani

et al. 2004

Journal of Biological Chemistry

108

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“…Hyperlipidemia represents a spectrum of metabolic disorders that can be found in many humans today. The manifestation of the hyperlipidemia is defined as an abnormal increase in one or more of the serum lipids profile such as either total cholesterol (TC), low-density lipoproteincholesterol (LDL-C) and triglycerides (TG) (Bencze et al, 2012). Hyperlipidemia need to be given special attention since it has been one of the greatest risk factors that contributes to the prevalence and severity of coronary heart diseases (Sudha et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Anti-hyperlipidemic Activity of Methanolic Extract of Impatiens Balsamina L. in Hypercholestrolemic Induced Sprague Dawley Rats

Fattepur

Nilugal

Balan

et al. 2018

Proceedings of BROMO Conference

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Background & Aim: The occurrence of hyperlipidemia, is currently increasing at a remarkable rate throughout the world. Hyperlipidemia graded as one of the greatest risk factors that contributes to the prevalence and severity of life threatening coronary heart diseases. Medicinal plants and their products are safer than their synthetic counterparts, including those involved in the anti-hyperlipidemic drugs statins. Impatiens Balsamina (IB) is used medicinally for various ailments. No study was carried out on the anticholesterol activity of IB. Objective: To study anti-hyperlipidemic activity of methanolic extracts of IB (MEIB) in hypercholesterolemia induced Sprague Dawley rats. Materials & Method: MEIB leaves were prepared using maceration method. Toxicity study was carried out using OECD guidelines. Hypercholesterolemia in rats was induced by using 6% of lard oil, 2% of cheese and egg yolk. Two different doses 200 and 400mg/kg of MEIB were used to study for anti-hyperlipidemic activity. Histopathological study was carried out in rats. Results: No mortality was observed even up to 2g/kg. Only 400mg/kg of MEIB statistically decreased in total cholesterol (P<0.05), LDL-cholesterol (P<0.05) and an increase in HDL-cholesterol (P<0.05) as compared to the positive control. Histopathology study revealed that 400mg/kg MEIB leaves administered group have mild steatosis and no inflammation as compared to control group. Conclusion: MEIB could be a potential herbal medicine as adjuvant with existing therapy for the treatment of hyperlipidemia.

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“…The prevalence of familial hyperlipoproteinemias (1)(2)(3)(4) as well as the direct relationship between hyperlipidemia and atherosclerosis in the human population (4-7) has indicated a need for blood lipid lowering compounds. The compound 2-methyl-2-[p- (1,2,3,4- man (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). However the study of this compound in experimental animals having abnormal lipid patterns has been limited.…”

Section: Introductionmentioning

confidence: 99%

The hypolipidemic effect of SU‐13,437 in rats with natural endogenous hypertriglyceridemia

Lenz

Fleischman

1971

Lipids

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The oral administration of 25 mg 2‐methyl‐2‐[p‐(1,2,3,4‐tetrahydro‐1‐naphthyl)‐phenoxy] propionic acid (SU‐13,437) per kilogram body weight per day in two‐month‐old female rats with naturally occurring hypertriglyceridemia resulted in a 31% decrease (P<0.01) in the serum triglyceride concentration after 14 days of treatment, compared with littermate controls receiving diluent (Polyethylene glycol‐300) only. Phospholipid, cholesterol, free fatty acid, glucose, red blood cell and white blood cell concentrations were similar in the blood of treated and control animals after 14 days of treatment. Liver total and relative weight was increased as a result of SU‐13,437 treatment (P<0.01). The liver total lipid concentration per 10 gm liver decreased (P<0.05) due to a decrease in triglyceride (P<0.01), cholesterol (P<0.01), and free fatty acid (P<0.05) concentration following treatment. The relative liver glycogen concentration was elevated in treated rats at 7 (P<0.01) and 14 (P<0.05) days of treatment.

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Hypolipidemic Agents

Cited by 10 publications

References 250 publications

Molecular Characterization of the Microsomal Tamoxifen Binding Site

Molecular Characterization of the Microsomal Tamoxifen Binding Site

Anti-hyperlipidemic Activity of Methanolic Extract of Impatiens Balsamina L. in Hypercholestrolemic Induced Sprague Dawley Rats

The hypolipidemic effect of SU‐13,437 in rats with natural endogenous hypertriglyceridemia

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