Alpha‐ketoglutarate protects the liver of piglets exposed during prenatal life to chronic excess of dexamethasone from metabolic and structural changes

Abstract

Glucocorticoids play a role in the origin of the features of the metabolic diseases. Alpha-ketoglutarate (AKG) is defined as glutamine homologue and derivative, conditionally an essential amino acid. In the liver, glutamine serves as a precursor for ureagenesis, gluconeogenesis and acute phase protein synthesis The aim of the study was to determine the effect of AKG administered to piglets prenatally exposed to dexamethasone, on the structure of the liver and its metabolic function. Sows were administered with dexamethasone (3 mg/sow/48 h) from day 70 of pregnancy to the parturition, and then after the birth, the piglets were divided into the group administered with AKG (0.4 g/kg body weight) or physiological saline. Biochemical markers, lysozyme and ceruloplasmin serum activities, concentrations of selected free amino acids, macro- and microelements and histomorphometry of the liver tissue were determined. The total cholesterol concentrations in the sows and their newborns from the Dex groups were higher by 72% and 64%, respectively, compared with the control groups. Triacylglycerol concentration was higher by 50% in sows from the Dex group and 55% in the new-born piglets. Alpha-ketoglutarate administered to the piglets after prenatal influence of dexamethasone lowered the total cholesterol concentration by 40%, and enhanced aspartate by 41%, serine by 76%, glutamate by 105%, glutamine by 36%, glycine by 53% and arginine by 105%, as well as methionine and cystathionine, but increased the sulphur concentration compared with the control (p < 0.01). Intracellular space D decreased after AKG administration in comparison with the piglets from Dex/Control group not treated with AKG. Postnatal administration of AKG had a protective effect on liver structure, and lowered the total cholesterol concentration in piglets prenatally exposed to dexamethasone, and also influenced selected macro- and microelement serum concentrations and amino acids plasma concentration.

The effect of dietary administration of 2-oxoglutaric acid on the cartilage and bone of growing rats

“…1); however, no differences were observed in the absolute weight of the bones examined or in the weight of any of the other organs (except the liver) when compared with the C group. The increase in absolute liver weight after 2-Ox administration may be a reflection of the increase in cell volume, intercellular space, average size of the nuclei, as well as the number and total area of nuclei of liver cells, which was observed in our previous study (Śliwa et al ( 33 ) ). Such changes in liver histology, leading to an increase in the weight and volume of this organ, according to Haussinger et al ( 34 ) , are related to glutamine metabolism.…”

Effects of maternal treatment with β‐hydroxy‐β‐metylbutyrate and 2‐oxoglutaric acid on femur development in offspring of minks of the standard dark brown type

“…The doses of 2‐Ox and HMB were determined in previous studies (Śliwa, ; Śliwa et al., ; Świetlicka et al., ; Tatara et al., ).…”

“…Their role in pre‐natal programming is still investigated in livestock (Śliwa, Kowalik, et al. ; Śliwa, Tatara, et al., ; Śliwa, Tatara, Nowakowski, Pierzynowski, & Studziński, ; Śliwa, ; Śliwa, Tatara, & Pierzynowski, ; Śliwa, Dobrowolski, Siwicki, & Pierzynowski, ; Śliwa et al., ; Śliwa, Adaszek, Tatara, & Dobrowolski, ; Tatara, Śliwa, & Krupski, ; Tomaszewska & Dobrowolski, ; Świetlicka et al., ). There is no knowledge about their effect on production results in fur animals.…”

“…In mammalian cells, glutamine is a key between carbon metabolism of carbohydrates and proteins and plays an important role in the growth (Kowalik et al., ; Neu, Shenoy, & Chakrabarti, ). It improves nitrogen balance and preserves the concentration of glutamine in skeletal muscle (Boelens, Nijveldt, Houdijk, Meijer, & Van Leeuwen, ; Calfee & Fadale, ; Pierzynowski & Sjodin, ; Williams, Abumrad, & Barbul, ; Śliwa et al., ). It must be emphasized that 2‐Ox administered enterally is utilized directly not only through different bacterial species but also through intestinal cells and is converted into glutamine, improving protein synthesis in the skeletal muscle (Boelens et al., ; Śliwa, Tatara, Nowakowski, et al., ; Williams et al., ).…”

Effect of HMB and 2-Ox administered during pregnancy on bone properties in primiparous and multiparous minks (Neivison vison)

“…2-Ox administered per os has positive effects on prenatal or postnatal skeletal development and growth progress in animals, e.g. post-hatching turkeys (4,11,16,(27)(28)(29)(30). 2-Ox also exerts a protective effect against the negative action of dexamethasone on bone and cartilage in intrauterine restricted animals (30).…”