Bone development of suckling piglets after prenatal, neonatal or perinatal treatment with dexamethasone.

In mammals, the release from growth-inhibiting conditions results in catch-up growth. To investigate animal evidence for whether prenatal dexamethasone (DEX) treatment leads to the development of growth restriction especially reduced mineralization of skeleton, and release from it leads to the phenomenon of catch-up, piglets were prenatally exposed to DEX (3.0 mg/sow per day(-2)) during the last 24 days of prenatal life and tested further in two different ways: discontinued at birth and continued administration of DEX (0.5 mg/kg day(-2)) to piglets through 30 days of neonatal life. Using dual energy X-ray absorptiometry methods, bone mineral density (BMD) and bone mineral content (BMC) were measured. The three-point bending test was applied to determine the mechanical properties of the bones. Furthermore, geometric properties of the bones were assessed. Serum concentration of osteocalcin (OC) was determined. Histomorphological analysis of the ribs was also performed. The consequences of neonate DEX treatment and in utero DEX exposure were reflected in a dramatic decrease of BMD, BMC and blood serum OC concentration and geometric parameters of piglets' bones. Prenatal action of DEX during the last 24 days of pregnancy resulted in continued neonatal modification of bone tissues, thus diminishing bone quality, and negatively influenced structural development and mechanical properties, finally increasing the risk of fractures of ribs and limb bones. Prenatal DEX treatment limited to the last 24 days of foetal life did not reduce the term birth weight and the growth of suckling piglets followed up to 30 days of neonatal life, and catch-up in bone mineralization did not occur.

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

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 quercetin on pro-apoptotic activity of cisplatin in HeLa cells.

It is well known that some tumour cells are very resistant to chemotherapy-induced cell death which indicate poor prognosis for patients. Thus the aim of the present study was to investigate the effect of quercetin on pro-apoptotic activity of cisplatin in human cervix carcinoma cells (HeLa). Three variants of experiments were performed. In the first one cells were incubated with studied drugs separately for 8 and 24h. In the second, drugs were added to the culture medium simultaneously. In third cisplatin or quercetin addition was followed by subsequent quercetin or cisplatin treatment, respectively. We observed different apoptotic effects, dependent on the drug succession. Preincubation of cells with quercetin followed by cisplatin treatment appeared to be the most effective and was correlated with strong activation of caspase-3 and inhibition of both heat shock proteins (Hsp72) and multi-drug resistance proteins (MRP) levels. Our results indicate that quercetin pretreatment sensitizes HeLa cells to cisplatin-induced apoptosis in HeLa cells.