HISTOPATHOLOGIC AND ULTRASTRUCTURAL ALTERATIONS OF WHITE LIVER-DISEASE IN SHEEP EXPERIMENTALLY DEPLETED OF COBALT

Many cobalt-deficient sheep develop Liver lesions known as ovine ''whi te liver'' disease, but the etiology of these changes is controversial . It has been suggested that cofactors are required for development of liver damage in cobalt-deficient sheep. In this study, one group of l ambs (n=5) was fed a diet low in cobalt (4.5 mu g/kg) while a group of control lambs (n=4) received the same diet after it had been suppleme nted with cobalt (1000 mu g/kg). All cobalt-depleted lambs had reduced growth rate, anorexia, lacrimation, and alopecia, and they eventually became emaciated (mean body weight at end of study: 83% of initial bo dy weight). Plasma concentrations of bilirubin and serum activity of g lutamate-oxaloacetate transferase were elevated in these animals, whil e plasma concentrations of vitamin B-12 were reduced (less than 220 pm ol/L from day 42). Fatty degeneration of the liver associated with red uced concentrations of vitamin B-12 (14.5 pmol/g) was seen in these an imals at necropsy at 196 days. Microscopic liver lesions included accu mulation of lipid droplets and lipofuscin particles in hepatocytes, di ssociation and necrosis of hepatocytes, and sparse infiltration by neu trophils, macrophages, and lymphocytes. Ultrastructural hepatocytic al terations included swelling, condensation and proliferation of mitocho ndria, hypertrophy of smooth endoplasmic reticulum, Vesiculation and l oss of arrays of rough endoplasmic reticulum, and accumulation of Lipi d droplets and lipofuscin granules in cytoplasm of hepatocytes. No liv er lesions were seen in control lambs. The results of this study indic ate that cofactors are not a prerequisite to development of hepatic da mage in cobalt-deficient sheep. Reduced activities of the vitamin B-12 -dependent enzymes, methylmalonyl CoA mutase and methionine synthase, and lipid peroxidation are of likely pathogenetic importance in the de velopment of the lesions.