Bull Vet Inst Pulawy 49, 343-348, 2005 INFLUENCE OF ALPHA-KETOGLUTARATE ON BONE MINERAL DENSITY OF THE FEMUR IN PIGLETS SYLWESTER KOWALIK, RAFAŁ S. FILIP 1 , EWA ŚLIWA, MARCIN R. TATARA, STEFAN G. PIERZYNOWSKI 2 AND TADEUSZ STUDZIēSKI Department of Animal Physiology, Faculty of Veterinary Medicine, Agricultural University of Lublin, 20–033 Lublin, Poland 1 Department of Metabolic and Degenerative Diseases of Bone Tissue, Institute of Agricultural Medicine, 20–950 Lublin, Poland 2 Department of Cell and Organism Biology, University of Lund, SE-223 62 Lund, Sweden e-mail: sylvester@wp.pl Received for publication May 24, 2005. Abstract The aim of this study was to determine the influence of daily oral administration of alpha-ketoglutarate (AKG) on bone mineral density of the femur and concentration of 17-ȕ- oestradiol in blood plasma during 70 d of postnatal life in piglets. All the animals were kept under standard rearing conditions. AKG was administered orally from the 1 st d of life, while the control piglets were treated in the same way and time with physiological saline. The experimental and control groups were assigned to 6 age subgroups: 3, 14, 21, 35, 56 and 70 d of life. The animals from both groups were euthanised, then bone samples were collected and frozen at –25 o C until further analyses. Using dual-energy x-ray absorptiometry (DEXA method) bone mineral density of the femora was estimated. Additionally, 17-ȕ-oestradiol concentration in blood plasma was assayed using RIA-test. The obtained results indicate positive influence of enteral AKG administration on bone mineral density of the femur in piglets. Moreover, AKG increased the level of 17-ȕ-oestradiol in blood plasma in post-weaned piglets. Key words: piglets, alpha-ketoglutarate, femur, bone mineral density, 17-ȕ-oestradiol. Under physiological conditions, maintenance of skeletal mass is the result of a tightly coupled process of complex multi-interactions between genetic, hormonal, dietary, and mechanical factors (1, 2, 3, 4, 13, 16, 20, 22). Diseases of the skeletal system, including osteoporosis, arise when delicate balance between these factors is disrupted, as, for example, in postmenopausal women, when oestrogen level decreases dramatically with the cessation of ovarian function. In recent studies, oestrogen deficiency is considered one of the main factors leading to bone loss (12, 17). A better understanding these relationships is very important and necessary for the identification of the deterioration of the skeleton and, in consequence, fracture risk. The important role of glutamine in the neonatal period of life inclined to undertake experiments on the influence of AKG, as a precursor of glutamine, administered orally on the general development with special direction to the skeletal system in piglets (10, 23). In mammals, glutamate is the only amino acid that can be formed by reductive amination of its ketoacid namely α- ketoglutaric acid (10, 15). Recent studies reported beneficial effects of AKG on bone geometrical and mechanical parameters but the mechanism of this interactions is still unknown (6, 7, 9, 19, 24, 26). It is well documented that AKG serves many functions in the organism. For example, it plays a central role in Krebs cycle, stimulates protein synthesis and inhibits protein degradation. It is also a main source of energy for enterocytes and immune cells (8, 24, 25). Moreover, AKG activates a hydroxylation of proline to hydroxyproline, one of the part of type I collagen, which is the main component (about 95%) of bone matrix (8). The skeletal system development and its mineralisation from experimental point of view is still not explained sufficiently because of lack of experimental animal model. Piglets seem to fulfil this gap. This paper revealed up-to-date findings on AKG influence on bone structural properties and changes of 17-ȕ-oestradiol in blood plasma in pre- and post-weaned piglets. Material and Methods Experimental design and sampling procedu- re. The experiment was performed on 120 piglets of Large Polish White breed. The animals were housed in piggery under standard rearing conditions with constant access to fresh water. After weaning, the piglets were fed standard commercial diets twice a day at 7.00 a.m. and 3.00 p.m. The piglets were divided into two equal