Src Family Kinases Inhibition Ameliorates Hypoxic-Ischemic Brain Injury in Immature Rats

Hypoxic-ischemic (HI) injury is one of the initial factors contributing to neonatal brain injury. Src family kinases (SFKs) are considered to act as molecular hubs for N-methyl-d-aspartate receptor (NMDAR) regulation and participate in the HI injury process. The objectives of this study were to evaluate the levels of phospho-Src (p-Src), the relationship between NMDARs and SFKs, and the effects of SFK inhibition on an immature rat HI brain injury model. The model was induced in 3-day-old Sprague–Dawley rats using the Rice-Vannucci model operation. The level of p-Src was evaluated using Western blotting. The association of NMDARs with SFKs was detected using Western blotting and coimmunoprecipitation. After intraperitoneal injection of 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP2), an SFK-selective inhibitor, neuropathological changes were observed by performing H&E and immunofluorescence staining, and the neurological functions were assessed using the following behavioral tests: modified neurological severity score, open field test, and Morris water maze test. The levels of p-Src first decreased at 0 h after injury, increased at 2 h after injury, and continuously decreased from 6 h to 3 days. Along with the increased p-Src levels observed at 2 h after injury, the phosphorylation of NMDAR subunit NR2B at tyrosine 1472 was increased. Following the administration of PP2, the increased p-Src and NMDAR-2B levels detected at 2 h after injury were decreased, and tissue injury and myelin basic protein expression were improved at 7 days after injury. The PP2 intervention improved the performance of injured rats on behavioral tests. In conclusion, we determined the patterns of p-Src expression after HI brain injury in immature rats and showed a relationship with the activated NMDA receptor. The inhibition of p-Src ameliorates neuropathological changes and damages neurological functions induced by HI injury.

Study of the skin-resorptive effect of a skin antiseptic based on polyvinylpyrollidone-iodineОценка эффективности профилактических дезинфекционных мероприятий на основе комплексного анализа микробиома мест содержания служебных собак

The skin-resorptive effect of a skin antiseptic based on polyvinylpyrollidone-iodine on immature rats of different ages was studied.The skin-resorptive effect of the drug in doses of 5.0 and 0.5 g/kg was revealed on 2–6 week-old rats. The animals showed changes in thyroxine and thyroid-stimulating hormone, as well as general toxic indicators. Absorption of the drug through the skin at a dose of 0.5 g/kg on 4–8 week old rat pups has not been established. The rationale for the use of a skin antiseptic for the hygienic treatment of hands containing PVP-iodine in the age group of children from 8 years old is given. Keywords: toxicity, skin-resorptive effect, immature white rats, skin antiseptic, iodine, thyroxine, thyroid-stimulating hormone.

Diazinon exposure reduces bone mineral density in adult and immature rats: A histomorphometric and radiographic study

Diazinon has been widely used as a domestic and agricultural pesticide. This study examined the effects of diazinon on bone mineral density (BMD) of mature and immature rats. For this purpose, 24 adult Wistar rats (male; 8 weeks old) were initially divided into four groups ( n = 6). Corn oil was used as the control while diazinon at 15, 30, and 45 mg/kg in corn oil was given to mature rats via gavage per day. Since these dosages were lethal for the immature rats, 12 immature Wistar rats (male; 4 weeks old) ( n = 6) were gavaged with corn oil as control and 5 mg/kg of diazinon in corn oil. The animals were sacrificed on day 28 with their left femur bones removed for histomorphometric studies. BMD was measured in the right femur, using standardized radiographs in the femoral head, femoral neck, greater trochanter, and shaft. The Image J Program was used for measuring the bone lamellae and epiphyseal growth plates. The results of this study for the first time revealed that diazinon reduced BMD in both adults and immature rats. Diazinon exposure was associated with diminished trabecular and cortical bone density. Correspondingly, our results indicated that in immature rats, DZN led to the reduction in the epiphyseal growth plate width, both in the proliferation and hypertrophic zones. These results suggested that diazinon might be associated with impaired bone longitudinal growth as well as bone metabolism in adults.

Increased Testicular Insulin-like Growth Factor 1 is Associated with Gonadal Activation by Recombinant Growth Hormone in Immature Rats

To understand the mechanism of precocious sexual maturation following prepubertal growth hormone (GH) therapy, the effects of recombinant human GH (rhGH) on the kisspeptin-gonadotropin-releasing hormone-luteinizing hormone (GnRH-LH) system in the hypothalamus-pituitary axis, systemic and testicular insulin-like growth factor-1 (IGF1), spermatogenesis and Leydig cell steroidogenesis, and circulating testosterone levels were examined in immature rats. Following daily injection of rhGH (1 or 2 IU/kg) from postnatal day (PND) 21 to PND 23 or 30, testicular steroidogenic pathway genes and spermatogenesis marker genes mRNA levels, the number and size of HSD17B(+) Leydig cells, and blood testosterone levels in the rhGH rats were significantly higher than those of controls on PNDs 24 and 31. Hypothalamic Kiss1 and Gnrh1 mRNA in the rhGH rats were significantly higher than those in the controls on PND 24, indicating early activation of hypothalamic kisspeptin-GnRH neurons by rhGH. Hypothalamic Igf1 mRNA levels in rhGH rats were significantly higher than those in the controls on PND 24 but significantly lower than those in controls on PND 31. Testicular Igf1 mRNA levels were significantly higher in rhGH rats than in the controls on PNDs 24 and 31 whereas liver Igf1 mRNA levels and circulating IGF1 levels were not. In progenitor Leydig cells, rhGH significantly increased the Igf1 and steroidogenic pathway genes mRNA levels and the testosterone production. Therefore, local increases in testicular IGF1 might be an important mediator of gonadal activation via steroidogenic activation of Leydig cells in immature rats given rhGH.

Bilobalide Enhances AMPK Activity to Improve Liver Injury and Metabolic Disorders in STZ-Induced Diabetes in Immature Rats via Regulating HMGB1/TLR4/NF-κB Signaling Pathway

This study was aimed at examining the effect and underlying mechanisms of bilobalide (BB) on hepatic injury in streptozotocin- (STZ-) induced diabetes mellitus (DM) in immature rats. Immature rats (one day old) were randomly divided into five groups: group I, control nondiabetic rats; group II, STZ-induced, untreated diabetic rats; groups III/IV/V, STZ-induced and BB-treated diabetic rats, which were intraperitoneally injected with BB (2.5 mg/kg, 5 mg/kg, or 10 mg/kg) after 3 days followed by STZ treatment. We observed that BB improved the histopathological changes and maintained normal glucose metabolism, blood lipid, and liver function indicators, such as fasting blood glucose, obesity index, HbA1c, HOMA-IR, fast serum insulin, adiponectin, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), aspartate transaminase (AST), and alanine transaminase (ALT) in STZ-induced DM in immature rats by a biochemical analyzer or ELISA. Meanwhile, Western blot analysis showed that in STZ-induced DM immature rats, BB decreased the expression of apoptosis-related proteins Bax, cleaved caspase-3, and cleaved caspase-9 while enhancing the Bcl-2 expression; BB downregulated the expression of ACC related to fat anabolism, while upregulating the expression of CPT-1 related to fat catabolism. Strikingly, treatment with BB significantly increased the expression of AMPKα1 as well as inhibited HMGB1, TLR4, and p-P65 expression in hepatic tissues of immature DM rats. AMPK inhibitor (compound C, CC) cotreated with BB undermined the protective effect of BB on the liver injury. The results of the present study suggested BB may have a significant role in alleviating liver damage in the STZ-induced immature DM rats.

ENGLISH VERSION: AGE FEATURES OF RADIOACTIVE IODINE (131I) ABSORPTION BY RAT THYROID GLANDS IN CORRECTION OF THE DIETARY IODINE DEFICIENCY WITH ORGANIC IODINE

The structure of endocrine morbidity is characterized by a significant spread of thyroid pathology. The insufficient efficacy of inorganic iodine drugs poses the problem of search for new means for iodine deficiency treatment and prevention. Given the progressive aging of the population in economically developed countries, the purpose of the study was to clarify the effect of organic iodine on the features of absorption and elimination of radioactive iodine from the thyroid glands of variously aged rats in the conditions of iodine deficiency in the diet. The study was performed on nonlinear white male rats in two series of studies that were kept on iodine-deficient isocaloric starch-casein diet for 60 days: the first series included two groups of old rats weighing 0.400-0.450 kg, the second series – two groups of sexually immature rats weighing 0.060-0.090 kg. There were 5 rats in each group. In animals of the experimental groups in each series, 10% of casein in the diet was replaced with organic iodine, which came with iodine-protein preparation from the red Black Sea algae Phyllophora nervosa. The functional state of the thyroid gland was studied using the Sodium Iodide Na 131 I Injection drug. The dosimetry was performed using the STS-6 Geiger-Muller Detector. Radioindication of the thyroid gland was carried out after subcutaneous administration of 0.1 ml of 131I solution at the following time intervals: 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 hours after administration of 131I. The study results were presented as a percentage of the radioiodine dose administered, adjusted for natural radioactivity background and the radioactive decay of the drug. It was found that in the iodine deficiency conditions, the thyroid glands of old rats have higher rates of radioiodine absorption and a lower rate of its excretion than the glands of immature rats, which indicates their lower iodine reserve and greater liability to iodine deficiency pathology. Intake of organic iodine regardless of the rats’ age is accompanied by a decrease in radioiodine accumulation and acceleration of its excretion from the thyroid gland, which indicates a decrease in functional stress, but the glands of older rats absorb more iodine and excrete it more slowly, indicating less effective correction of iodine deficiency with age. Reduced functional activity of the thyroid glands in old rats can be used as a sensitive changes marker for the in-depth study of thyrotropic and thyroid disrupting effects.