Zinc toxicity in the fowl: ultrastructural pathology and relationship to selenium, lead and copper

Some dietary, enzymic and morphological relationships of selenium, lead and copper to the toxicity of zinc in adult female fowls have been investigated. The anorexia, pancreatic and gizzard lesions which resulted from incorporating 20,000 and 25,000 mg zinc as zinc oxide per kg diet were not prevented by concurrent daily injections of 0.3 mg selenium or the addition of 500 and 2500 mg lead per kg diet. Anorexia and gizzard lesions were also produced by feeding copper sulphate at levels of 2000 and 4000 mg per kg of diet but the pancreas was unaffected. This suggests that zinc may act directly on the pancreas rather than by interfering with the protective function of the selenium. Glutathione peroxidase activity significantly decreased in the blood when zinc-containing diets were fed and selenium injection prevented this. Activity in the liver was also reduced but in the pancreas it was increased by both zinc and zinc plus selenium. Electron microscopy showed that there was an infiltration of heterophils in the gizzard of birds given excess zinc but otherwise there was little qualitative difference in surface cell ultrastructure from the degenerative processes of the normal desquamatory sequence. Pancreatic exocrine cells had reduced numbers of zymogen bodies, distended rough endoplasmic reticulum, many cytoplasmic small, electron-dense bodies and large autophagic vacuoles, sometimes leading to cell death. The acinar lumina were dilated and there was periacinar fibrosis. The significance of these lesions as an indication of zinc-induced interference with pancreatic protein synthesis and membrane integrity is discussed.