HEPATIC TOTAL 3-ALPHA-HYDROXY BILE-ACIDS CONCENTRATION AND ENZYME-ACTIVITIES IN PREDNISONE-TREATED DOGS

High serum alkaline phosphatase (ALP) activity is considered a sensiti ve marker of cholestasis in most mammalian species, including dogs. In duction of high serum ALP activity in association with cholestasis is dependent on high hepatic bile acids concentrations. Treatment of dogs with glucocorticoids also results in high serum ALP activity. The pos sible causal relation between serum ALP activity and bile acids concen tration was investigated in dogs treated with glucocorticoids. The rel ation of glucocorticoid treatment to changes in the activity of indivi dual ALP isoenzymes, alanine transaminase (ALT) and gamma-glutamyltran sferase (GGT) also was investigated. Eight conditioned dogs were given 4 mg of prednisone/kg of body weight, IM, daily for 10 days. Blood sa mples were taken prior to treatment and on treatment days 3, 5, 7, and 10. Liver tissue was then taken from each dog. Serum total ALP activi ty was significantly (P < 0.05) high at day 3 in prednisone-treated do gs. Isoenzyme analysis indicated that this increase was attributable t o an increase in the liver ALP isoenzyme (LALP). Significant increases in serum corticosteroid-induced ALP (CALF) and bone ALP were first ob served on days 7 and 10, respectively. Serum ALT and GGT activities we re significantly increased by day 5. Increased serum or hepatic tissue bile acids concentrations were not observed in prednisone-treated dog s, compared with values in 8 clinically normal (control) dogs, but wer e high in 3 dogs with complete bile duct ligation. Hepatic activities of LALP, CALP, and GGT were higher in prednisone-treated dogs than val ues in controls, indicating probable increased hepatic synthesis of th ese enzymes. Hepatic ALT activity was not increased. The ratio of seru m to tissue LALP activity was increased in prednisone-treated dogs, co mpared with values in controls, indicating that LALP may have been pre ferentially released into serum. There was no difference in the ratio of serum to liver GGT activity between prednisone-treated dogs and con trols. The LALP and GGT ratios were increased in bile duct-obstruction dogs. It was concluded that, although LALP is the principal ALP isoen zyme in serum during the first 10 days of prednisone treatment, hepati c bile acid concentrations are not increased and, therefore, are not l ikely to be responsible for induction and release of ALP into serum. P rednisone may, therefore, be directly responsible for induction of ALP activity in dogs treated thusly.