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KMID : 0378019670100120029
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New Medical Journal
1967 Volume.10 No. 12 p.29 ~ p.42
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Effect of Corticosteroids on the Hepatic Cell and Bile Secretion
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Abstract
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It is evident by clinical observation that the jaundice of hepatitis often decreases rapidly following the administration of adrenecorticosteroids. Patterson, et al. studied this problem directly and concluded that cortisone possesses choleretic and hydrocholeretic capacities. Against this interpretation are several studies which have not confirmed a choleretic effect. However, the observation of Gans and McEntee that repeated administration of large doses of prednisolone resulted in an increase in hepatic bile flow is of interest. They also observed a peculiar hepatic lesion characterized by the presence of large areas of vacuolar degeneration in liver sections from the prednisolone treated animals. The pre-sent study was performed to explore the status of hepatic bile secretion as well as Iiver cell during the chronic administration of glucocorticoids or other steroids, using secretory stimulants or histologic technique.
Mongrel dogs of both sexes, weighing 8 to 14 kg were employed in this experiment and divided into follo-Wing groups:
Group 1. Control: 10 dogs served as nontreated controls.
Group 2. Glucocorticoid treated: 17 dogs were used. Cortisone acetate, prednisolone, or dexamethasone was administered intramuscularly to each subgroup of three dogs for 10 da rs, at a daily dose of 8.0 mg/kg, 2.0 mg/kg and 0.4 mg/kg, respectively. In addition three adranalectomized dogs and five prednisolone treated animals for successive liver biopsies were used.
Group 3, Desoxycorticosterone treated: Desoxycorticosterone acetate (DOCA) was administered intramuscularly to a group of three dogs for 10 days, at a dose of 4.0 mg/ kg daily.
Group 4. Testosterone treated: Testosterone propionate was administered at a dose of 8.0 mg,/kg daily as Group 3.
At the-end of the experimental_ period, food was withheld from each dog for 15 hours. Each dog was then anesthetized with sodium pentobarbital and the trachea was carnnulated. A laparotomy was performed. The cystic duct was ligated and a polyethylene tube of an appropriate size (PE 190, Clay-Adams Co.) was passed into the common duct and ligated securely in place. Physiological saline solution, pH 8.0, was infused throughout the experiment. Hepatic bile collected for one hour and then bile samples were obtained following secretory stimulants such as secretin, 10 u, pancreozymin 10 u, and 100 mg of cholates, e.g., sodium taurocholate, sodium cholate or sodium desoxychoiate.
Samples of bile were taken during 2 consecutive 10 minute periods following the administration of the secretory stimulants.- Bile acid and bilirubin content were determined according to the methods of Irvin ct al. and Magee et al., respectively. Total bile acid and bilirubin outputs in bile have been expressed in terms of mg per 10 kg of body weight per 10 minutes. Serum amylase and lipase ;were determined by the methods as those described previously (Hong et al). The method for serum GOT, GPT, or Alkaline Phosphatase were followed by the technique described in Sigma Bulletin. Glycogen content were determined by the Anthrone Adapted method. The liver strips were dried in the oven at 80C to constant weight. Ash was obtained following 24hrs incubation in furnace at the temperature of 800-1,000C.
Results
Hepatic bile flow: Although the total bile acid and bilirubin in hepatic bile following the installation of total biliary fistulas in dogs decreased with a time course, the bile flow during early 2 to 3 hours after preparation was relatively consistence.
The administration of corticosteroid to dogs did not accompany any observable responses except an irrespectable minor changes of body weight. However, a significant changes of hepatic bile flow and bile acid content in response to secretory stimulants were noticed in glucocorticoid-treated animals.
In control animal the bile flow was increased following secretin or pancreozymin stimulation and both the bile flow and bile acid content were significantly increased by the stimulation with the choleretics, taurocholate and cholate. After treatment with DOCA the flow increase was marked but bile acid content was greatly reduced.
Following administration of glucocorticoid for 10 days the bile flow in response to secretin or pancreozymin was increased more than double folds in comparison with that of control values, but the bile acid content in bile were essentially unchanged. The response of bile flow induced by the choleretics, particularly by sodium cholate was enhanced in glucocorticoid-treated animals. Unlike control in these animals bile acid content in bile was not raised by the taurocholate administration.
In DOCA treated group the bile secretion after various secretory stimulation was approximately similar to that seen in cortisone-treated animal. The response of bile secretion in testosterone-treated animals showed little difference from control and the flow was rather erratic.
1 Hepatic weight: The weight of the liver as a fraction of body weight in the case of animals receiving glucocorticoids daily for 10 days was significantly increased to 46.4 g/kg body weight from the control value of 37.8 g/kg body weight. The hepatic weight was also increased in the adrenalectomized animals receiving supplementary cortisone for 2 weeks. The testosterone-treated animals or DOCA treated animals showed reduction of liver weight.
The weight of pancreas was relatively constant in all animals and the weight of the kidney was decreased slightly in case of prednisolone, dexamethasone, DOCA treated animals and adrenalectomized animals with supplementary cortisone.
Histological findings: Histological examination revealed in case of animals receiving glucocorticoids a peculiar changes characterized by the presence of large areas of ballooning and vesicular changes in liver. Special stain demonstrated that the material distending the hepatic cells are glycogen. When serial biopsies were taken the appearance of vesicular changes in liver cell was increased during prednisolone administration and it faded rapidly after stopping the treatment. The glycogen content in liver was increased during prednisolone treatment and decreased after cessation of treatment same as the changes in the hepatic cells. The ballooning and vesicular cytoplasmic changes in liver were observed in cortisone, prednisolone and dexamethasone-treated animals but not in the normal control, testoste-cone-treated or DULA injected animals. The degrees of the change were most marxea in aexametha. sone-treated animals and followed by prednisolone and cortisone-treated animals.
Summary
1. The administration of glucocorticoids to dogs resulted in a significant increase in the hepatic bile secretion in response to secretory stimulants. .
2. The secretory response of hepatic bile in testosterone-treated animals was not changed and the response was increase in DOCA-treated animals.
3. A significant increase of liver weight was induced by the animals receiving glucocorticoids for 10 days. Other organ weights were not changed by the steroid treatment except slight reduction of kidney weights in prednisolone, dexamethasone, DOCA treated animals as well as adrenalectomized animal supplemented with cortisone.
4. The presence of large areas of ballooning and vesicular changes of liver cell was seen in glucocorticoid-treated animals, particularly in cases of dexamethasone and prednisolone administration. Both vesicular changes of liver cell and liver glycogen content were increased by the repeated administration of prednisolone and reduced by the cessation of treatment. Special stain and liver glycogen determination demonstrated the material distending the liver cell was glycogen.
These findings indicate that chronic administration of glucocorticoid results in choleretic and hydrocholeretic actions, and increases liver weight and hepatic glycogen content. (Supported by grant No. 65-847, China Med. Board of New York)
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