Influence of Lecithins on Autoxidation of Cholesterol From Aqueous Dispersions at 85°

Weiner, Norman; Bruning, Werner C.; Felmeister, Alvin

doi:10.1002/jps.2600620734

Cited by 5 publications

(2 citation statements)

References 9 publications

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“…Thus, in the present series of experiments, appreciable autoxidation of cholesterol was not demonstrable. This finding is consistent with studies showing that quantitative autoxidation of cholesterol in aqueous dispersions requires hours of incubation and elevated temperatures (Weiner et al, 1973;Kimura et al, 1976). To measure radioactivity bound to tissue, the arteries were digested in 1 ml of Protosol (NewEngland Nuclear).…”

Section: Methodssupporting

confidence: 87%

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Sensitization of isolated canine coronary arteries to calcium ions after exposure to cholesterol.

Yokoyama¹,

Henry²

1979

Circulation Research

103

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The abundance of membrane cholesterol is an important determinant of the functional properties of biomembranes. To determine whether arterial smooth muscle acquires altered contractile properties in a high cholesterol environment, isolated canine coronary arteries were exposed to cholesterol in stable aqueous solution. Cholesterol, 10(-12) to 10(-10) M, was an efficacious vasoconstrictor, as maximum contractions equaled those obtained with 15 mM KCl. Antiadrenergic interventions, including chemical sympathectomy in vivo with 6-hydroxydopamine and alpha- and beta-adrenergic blockade with phentolamine and L-propranolol (both 10(-6 M), did not significantly attenuate the contractions. However, responses to cholesterol were abolished completely by (+/-)-verapamil (10(-6) M). Cholesterol in picomolar concentration enhanced the constrictor effects of CaCl2 and KCl, both in the presence and absence of alpha- and beta-adrenergic blockade. Increases in tone in response to graded elevations in the CaCl2 concentration (0-2 mM) were augmented up to 1.5-fold by 10(-12) M cholesterol (P less than 0.01). Results indicate that cholesterol sensitizes isolated coronary arteries to external Ca2+ by a nonadrenergic mechanism. The findings are consistent with the hypothesis that acquisition of membrane cholesterol may alter the contractile properties of coronary arterial smooth muscle, a phenomenon that could play a role in the pathophysiology of atherosclerotic heart disease.

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Section: Methodssupporting

confidence: 87%

“…Cholesterol dispersed in aqueous solvents may undergo autoxidation (Weiner et al, 1973;Kimura et al, 1976). In addition, cholesterol may have affinity for highly reactive oxygen species that may be generated at membrane sites (Suwa et al, 1977).…”

Section: Discussionmentioning

confidence: 99%

Sensitization of isolated canine coronary arteries to calcium ions after exposure to cholesterol.

Yokoyama¹,

Henry²

1979

Circulation Research

103

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The pharmacokinetics of methotrexate after intravenous administration of methotrexate‐loaded proliposomes to rats

Park

Ahn

Yoon

et al. 1994

Biopharm & Drug Disp

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The pharmacokinetics and tissue distribution of methotrexate (MTX) were investigated after intravenous (i.v.) injection of free MTX (treatment I), MTX-loaded proliposomes (treatment II), and empty proliposomes mixed manually with free MTX (treatment III), 8 mg kg-1, to rats using an HPLC assay. After i.v. infusion in 1 min, the plasma concentration of MTX (Cp), the area under the plasma concentration-time curve (AUC, 639 versus 913 micrograms min mL-1), the terminal half-life (t1/2, 48.8 versus 397 min), the mean residence time (MRT, 8.40 versus 325 min), and the apparent volume of distribution at steady state (Vss, 98.1 versus 2800 mL kg-1) were significantly higher; however, the total body clearance (CL, 12.5 versus 8.76 mL min-1 kg-1), renal clearance (CLR, 4.49 versus 2.78 mL min-1 kg-1), non-renal clearance (CLNR, 7.50 versus 5.99 mL min-1 kg-1), and the amount of MTX excreted in urine (Xu, 808 versus 685 micrograms, p < 0.0948) were significantly lower from treatment II than from treatment I. This could be due to the fact that some of the MTX-loaded liposomes (formed immediately after hydration of MTX-loaded proliposomes) are entrapped in tissues and the rest are present in the plasma (higher MRT and Vss from treatment II), and MTX is slowly released from MTX-loaded liposomes (higher t1/2 from treatment II). In the present HPLC assay, the concentrations of MTX represent the sum of free MTX and MTX loaded in liposomes (higher Cp and AUC, slower CL from treatment II). After i.v. infusion in 1 min, some pharmacokinetic parameters, such as t1/2, MRT, and Vss, were significantly different between treatments I and III; however, the differences seemed to be smaller than those between treatments I and II. After 30 min from i.v. infusion, the tissue to plasma (T/P) ratios of MTX in kidney and stomach from treatment II were significantly lower than those from treatment I. This suggested that the i.v. administration of MTX-loaded proliposomes might have fewer side effects in the organs than that of free MTX. The mean amount of MTX loaded in MTX-loaded proliposomes was 2.54 mg/g proliposomes and the MTX was released slowly from hydrated MTX-loaded proliposomes when incubated with phosphate-buffered saline (PBS), rat plasma, or rat liver homogenate.

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Pharmaceutical Sciences — 1973: Literature Review of Pharmaceutics

Herd¹,

Haleblian²

1974

Journal of Pharmaceutical Sciences

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Influence of Lecithins on Autoxidation of Cholesterol From Aqueous Dispersions at 85°

Cited by 5 publications

References 9 publications

Sensitization of isolated canine coronary arteries to calcium ions after exposure to cholesterol.

Sensitization of isolated canine coronary arteries to calcium ions after exposure to cholesterol.

The pharmacokinetics of methotrexate after intravenous administration of methotrexate‐loaded proliposomes to rats

Pharmaceutical Sciences — 1973: Literature Review of Pharmaceutics

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