Observations Concerning the Production and Excretion of Cholesterol in Mammals

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Abstract
Seventeen rats were bled, fed 100 mg of cholesterol in 3 ml of olive oil, and bled again after 48 hours. The plasma samples, which were devoid of chylomicra, contained an average of 49 mg% of cholesterol before feeding and 61 mg% afterwards. Rats fed only olive oil (5) showed a similar absence of chylomicra and averaged 43 and 67 mg% of plasma cholesterol for the respective samples taken before and after feeding. Rats injected intravenously with India ink (8), rats injected with chromium phosphate (5), and those injected with sac-charated iron (5), but not fed oil or cholesterol, also showed similar minor increases in plasma cholesterol concentration in 48 hours, with no plasma chylomicra. When 15 rats were injected with India ink and also fed oil, plasma cholesterol again rose only from 54 mg% to 69 mg %; chylomicra were observed in this plasma. However, when India ink (11 rats) chromium phosphate (9 rats) or saccharated iron (15 rats) were injected repeatedly during that time in which cholesterol was being actively absorbed from an oral dose of 100 mg in 3 ml of oil, plasma cholesterol values rose, respectively, from 49 to 101 mg%, from 44 to 97 mg%, and from 47 to 91 mg%. Chylomicra were present in all these 48 hour samples. Liver sections from these experimental and control rats, processed as described below, showed fat and cholesterol deposits in hepatic cells and reticulo-endothelial cells of non-injected animals fed cholesterol and/or oil, whereas very little stainable fat or retractile cholesterol could be seen in liver sections from injected fed rats. Three series of 9 rats each were fed, respectively, 100 mg of cholesterol in 3 ml of oil; 100 mg of cholesterol and 150 mg of "Tween" detergent in 3 cc of normal saline; 3 ml of oil. A similar control series was starved. At 6,24, and 48 hours respectively after feeding, 3 rats of each series were sacrificed 1/2 hour after injecting India ink (to identify active reticulo-endothelial cells). Formalin fixed frozen sections of liver, spleen and lung were made, stained with Sudan IV and also some incubated at 55[degree] to crystallize cholesterol and stained with hematoxylin. These incubated sections were examined under polarized light for retractile bodies. The organs of starved rats did not show either Sudanophilic or retractile bodies. Similar negative findings were the case for spleen and lung in the 3 fed series. However, the livers of all animals of the 3 fed series at 6 hours contained Sudanophilic granules largely deposited between the parenchymal cells and in contact with ink aggregates. A similar finding was made with respect to retractile bodies. The majority of retractile bodies and Sudanophilic granules still persisted in this location at 24 hours, but some intracellular parenchymal staining was also evident at this time. At 48 hours the few Sudanophilic granules and retractile bodies present were entirely within the hepatic cells. The injection of India into 5 rats caused no change in liver function, as indicated by ability to excrete cholic acid, and brought about no histological evidence of hepatic cell injury. The authors conclude that the liver reticulo-endothelial cell of the rat is necessary to the normal disposition of plasma cholesterol of exogenous origin, since this cholesterol circulates as chylomicra, some of which normally are phagocytized before disposal.