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Accumulation and Metabolism of Iron-Dextran by Hepatocytes, Kupffer Cells and Endothelial Cells in the Neonatal Pig Liver^1,2,3,

Thomas J. Caperna^*,,, Mark L. Failla^*,,4, Norman C. Steele and Mark P. Richards

^* Department of Biochemistry and Nutrition, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061 Nonruminant Animal Nutrition Laboratory, Animal Science Institute, USDA, Beltsville, MD 20705 Vitamins and Minerals Nutrition Laboratory, Beltsville Human Nutrition Research Center, USDA, Beltsville, MD 20705

Treatment of newborn pigs with supplemental iron is a common procedure utilized to prevent neonatal anemia. The aim of this study was to investigate the hepatic distribution and intracellular metabolism of iron-dextran, a widely used colloidal-iron-carbohydrate preparation. Piglets were injected intramuscularly with iron-dextran (50 mg Fe/kg body wt) at 1 d of age. Hepatocytes and sinusoidal cells (Kupffer cells and endothelial cells) were isolated from iron-treated and control (uninjected) piglets at 2, 6 and 11 d of age. The concentrations of iron, copper and zinc in isolated cells were determined by atomic-absorption spectroscopy. In addition, the quantities of ferritin-protein and ferritin-iron were measured by immunoelectrophoresis and ionexchange chromatography, respectively. At 2 d of age, the concentration (µg/mg cell protein) of iron was 5-, 62- and 54-fold higher in hepatocytes, Kupffer cells and endothelial cells, respectively, isolated from iron-treated piglets than from control piglets. Hepatocytes, Kupffer cells and endothelial cells accumulated ferritin in response to iron-dextran treatment. Higher concentrations of ferritin-protein and ferritin-iron were present in Kupffer cells and endothelial cells than in hepatocytes at all times after treatment with iron-dextran. The percentage of cellular iron that was associated with ferritin, however, was greater in hepatocytes than in sinusoidal cells. Iron accumulated by all three liver cell types was mobilized to extrahepatic sites. Slight alterations in zinc and copper status of liver cells were evident at 11 d of age as a result of iron treatment.

KEY WORDS: • iron • supplemental iron • ferritin • hepatocytes • Kupffer cells • endothelial cells • neonatal pigs • zinc • copper

¹ This work was supported in part by grants from the Virginia Pork Industry Commission (to M. L. Failla) and the Sigma Xi Grants-in-Aid Program (to T. J. Caperna).

² A preliminary report of this work was presented at the 70th Annual Meeting of the Federation of American Societies for Experimental Biology, April 13–18, 1986, St. Louis, MO. Caperna, T. J. & Failla, M. L. (1986) Metabolism of supplemental iron by hepatocytes, Kupffer cells and endothelial cells in neonatal pig liver. Fed. Proc. 45: 1080 (abs. 5384).

³ Mention of trade names, proprietary product or vendor does not constitute a guarantee or warranty of the product by USDA or imply its approval to the exclusion of other products or vendors that may also be suitable.

⁴ To whom reprint requests should be sent at USDA, Beltsville.

Manuscript received 7 May 1986. Revision accepted 30 September 1986.