Tissue γ-glutamyl transpeptidase activity and hepatic ultrastructural alterations in dogs with experimentally induced glucocorticoid hepatopathy

Glucocorticoid hepatopathy was induced in 2 Beagle dogs with IM injections of prednisone, 4.4 mg/kg, given once daily for 14 consecutive days. Serum enzymatic activities were monitored and percutaneous hepatic biopsy materials were collected. A placebo-treated group of 2 Beagle dogs was given saline solution injections. Treated dogs showed clinical signs of Cushing's disease and alterations in mean serum enzymatic activities consistent with glucocorticoid hepatopathy. The γ-glutamyl transpeptidase activities in placebo-treated dogs were highest for kidney, less (but marked) for pancreas, and least for liver, gallbladder, jejunum, duodenum, spleen, heart, lung, skeletal muscle, and erythrocytes. In treated dogs, the γ-glutamyl transpeptidase activities were highest for pancreas and were decreased for kidney and slightly increased for the other tissues. Results of hepatic biopsy and necropsy examinations of treated dogs showed swollen, pale, friable hepatic parenchyma with hepatocytic cytoplasmic vacuolation and glycogen accumulation. Extrahepatic lesions included gastric ulceration, catarrhal enteritis, splenic and lymph node atrophy and lymphocytolysis, and vacuolation of adrenal cortical cells in the zona fasciculata. Ultrastructural study of liver from dogs with glucocorticoid hepatopathy indicated that the principle alterations were abundant glycogen accumulation and few mitochondria in hepatocytes.