The administration to rats of cholesta-3:5-dien-7-one

Abstract

The fact that cholesta-3:5-dien-7-one occurs in arteriosclerotic aorta and some other tissues, in small amounts (Hardegger, Ruzicka & Tagmann, 1943; Prelog, Ruzicka & Stein, 1943), and that it is not necessarily an artifact (Kantiengar & Morton, 1955a) makes it desirable to study the effect of administering it to animals. In the present work it has been given to rats orally at the rate of 25 mg./ rat. Absorption is slow and partial, but a little unchanged material reaches the liver; conversion into a similar compound (probably cholesta-4:6dien-3-one) occurs in the gut to an appreciable extent, but absorption of this substance is very poor. It has been shown (Kantiengar & Morton,1955b) that by feeding cholesterol (2 % ofdiet) the resulting fatty livers contain small, but significant, amounts of the 3:5-dien-7-one. One result of the present study is the finding that on an otherwise sterol-free diet providing 83.3 mg. dienone/rat/day, the part which reaches the liver is stored to only a minute extent and, although the digitonin-precipitable sterol becomes higher than in the sterol-free controls, it is quite comparable with that of normal rat liver. This may mean that the appearance of cholesta-3:5-dien-7-one in tissues is a result of excess cholesterol production or deposition. EXPERIMENTAL AnimaZs. Healthy adult male albino rats were used. They were given 12 g. rat cubes on each of 4 days before dosing.

Sterol Metabolism. I. 26-Hydroxycholesterol in the Human Aorta*

“…It must be emphasized that our detection of cholesta-3.5-dien-7-one in the present sterol fractions neither confirms nor denies the prior claims for its isolation from or detection in the human aorta (Hardegger et al, 1943;Kantiengar and Morton, 1955;Robertson, 1955), since our results apply here only to aortal polar sterol fractions initially more polar than cholesterol on column and thin layer chromatoplates. The ready dehydration of 7-ketocholesterol herein observed in relatively uncomplicated chromatographic procedures does support an artifact status for cholesta-3,5-dien-7-one recovered from tissues where controlled chromatographic observation of the several steps involved was not had.…”

“…7-Ketocholesterol has been detected or isolated as such or as its dehydration product cholest-3,5-dien-7-one from a variety of tissues, including the human aorta (Schoenheimer, 1932;Hardegger et al, 1943;Kantiengar and Morton, 1955;Brooks et al, 1966). However, the extent of air oxidation as a contributory process was either not considered by these investigators or else was rejected as a factor (Kantiengar and Morton, 1955). No prior effort is known to us which offers the careful chromatographic or other control work and attention to detail necessary to definitive conclusions on the matter.…”

“…Furthermore, the presence of desmosterol in aortal tissue of patients treated with triparanol has been reported (Blankenhorn et al, 1961;Hollander, 1961, 1965; Jose and Peak, 1963). Other sterols isolated from or detected in the human aorta include cholesta-3,5-dien-7- one (Hardegger et al, 1943;Kantiengar and Morton, 1955;Robertson, 1955), cholesta-4,6-dien-3-one (Hardegger et al, 1943;Robertson, 1955), 5a-cholestane-3/3,5,6/3-triol (Hardegger et al, 1943;Henderson and McDougall, 1954;Henderson, 1956), 7a-hydroxycholesterol (Hardegger et al, 1943;Henderson and McDougall, 1954; Henderson, 1956), 7/3-hydroxycholesterol (Henderson, 1956), 24or 25-hydroxycholesterol (Henderson, 1956), and 7-ketocholesterol (Schoenheimer, 1932;Brooks et al, 1966). More recently 26-hydroxycholesterol has been detected as a constituent of human atherosclerotic plaques (Steel et al, 1966;Brooks et al, 1966) and cholesteryl sulfate has been isolated from human aortal tissue (Drayer and Lieberman, 1967).…”