Efficacy of erythropoietin-pretreated mesenchymal stem cells in murine burn wound healing: possible in vivo transdifferentiation into keratinocytes.

BACKGROUND: Stem cells have shown promising potential to treat burn wounds. Erythropoietin was capable of promoting in vitro transdifferentiation of mesenchymal stem cells (MSCs). The aim of the study was to investigate possible role of erythropoietin-pretreated mesenchymal stem cells (EPOa/MSCs) in burn wounds healing and to evaluate its in vivo differentiation into keratinocytes. MATERIALS AND METHODS: Forty rats were utilised in this study divided into four groups (n = 10 for each). Control group (I), burn group (II), burn + MSCs, group (III), burn + EPOa/MSCs. 1 × 106 cells were injected locally for each 1 cm² of burn areas. Burn areas were followed-up morphologically. After 21 days of the experiment, the rats were euthanised, skin specimens were assessed biochemically, histologically and immunohistochemically. RESULTS: EPOa/MSCs enhanced significantly (p < 0.05) burn wound vimentin gene expression and level of interleukin (IL)-10 while decreased IL-1 and COX2 as compared to the burn group. Histologically, EPOa/MSCs improved epithelialisation despite stem cells' differentiation into keratinocytes was rarely detected by PKH26 red fluorescence. EPOa/MSCs promoted angiogenesis as detected by significant increase in VEGF and PDGF immunoexpression as compared to burn group. CONCLUSIONS: EPOa/MSCs may improve burn wound healing, probably through anti-inflammatory, immunomodulatory and angiogenic action. However, in vivo transdifferentiation into keratinocytes was rarely detected.

Effects of nicotine on rat adrenal gland: crosstalk between oxidative and inflammatory markers, and amelioration by melatonin.

Although the risks of smoking are well known, the effects of exposure to nicotine on endocrine functions remain unclear. We investigated the deleterious effects of nicotine on the adrenal gland and the mechanisms of these changes in rats. The role of melatonin in ameliorating pathological changes also was investigated. We used 24 rats divided into four groups of six: group 1, control; group 2, nicotine treated; group 3, nicotine and melatonin treated; group 4, melatonin treated. We used histology; immunohistochemistry of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and tyrosine hydroxylase (TH); measured oxidative and antioxidative markers, malondialdehyde (MDA) and glutathione (GSH); and performed real-time PCR for NF-κB 65, IL1-B and IL6. We also performed histomorphometric analysis. Indentation and lamellar separation of the adrenal capsule, vacuolated degenerated cells and lymphocytic infiltration were observed in group 2. Vacuolated cells and cells with pyknotic nuclei also were detected in the zona reticularis and medulla of the same group. We observed improved shape and cellular lining of the gland in groups 3 and 4. Widespread expression of iNOS, VEGF and TH, increased area percent collagen, decreased GSH (56%) and increased MDA, NF-κB, IL1-B and IL-6 were observed in group 2. All parameters were ameliorated in groups 3 and 4. The effects of nicotine on the adrenal gland can be attributed to oxidative and inflammatory stress; melatonin ameliorates these effects.

Effect of valproic acid administration during pregnancy on postnatal development of cerebellar cortex and the possible protective role of folic acid.

BACKGROUND: Valproic acid (VPA), one of the most important antiepileptic drugs, proved to be inevitable for epileptic pregnant women to limit the hazards of convulsions on the foetuses and mothers. Periconceptional folic acid supple-mentation was investigated to protect against several birth defects. However, its role against VPA cerebellar toxicity was not properly investigated. The present study was conducted to evaluate the protective effect of folic acid against VPA cerebellar neurotoxicity. MATERIALS AND METHODS: Twenty-four pregnant female albino rats were divided into three groups; group I (control group, did not receive any drugs), group II (given VPA at a dose of 50 mg/kg body weight once daily) and group III (given the same dose of VPA and 400 µg/kg of body weight folic acid once daily). Ten male offspring from each group were sacrificed at two ages: at 2 and 12 weeks after birth. Samples of cerebellar cortex were taken and prepared for light, electron microscopic examination, glial fibrillary acidic protein (GFAP) immunohistochemical study and histomorphometric analysis. RESULTS: The present study confirmed the neurotoxic effect of prenatal VPA on the cerebellar cortex, especially on Purkinje cells. The cells appeared shrunken, reduced in density, disorganised and surrounded by empty haloes. Nuclear damage and axon degeneration in the form of vacuolation, loss of organelles and absence of neurofilaments with myelin sheath depletion were detected. Concomitant supply of folic acid was shown to retain the normal architecture of Purkinje cells with their axons and nuclei. In many animals receiving folic acid, the thickness of all layers of the cortex increased up to that of the control groups, after being markedly reduced in VPA-treated groups. GFAP immunoreaction was also improved against the strong positive gliosis detected in VPA-treated groups. CONCLUSIONS: The present study confirmed the protective role of folic acid against the cerebellar neurotoxic effects of VPA prenatal exposure. It is recommended that folic acid supplements should be given to every epileptic pregnant mother treated with VPA. (Folia Morphol 2018; 77, 2: 201-209).

Efficiency of selenium in attenuating epididymal histopathological changes in hypercholesterolaemic adult rat.

BACKGROUND: Studies on sperm maturation, epididymal histology, or epididymal tubule physiology are significant parts in reproductive researches. The present study was aimed to evaluate the effect of induced hypercholesterolaemia on the epididymis of adult albino rats and to clarify the possible protective role of selenium. MATERIALS AND METHODS: Forty adult albino Wistar rats were divided into four groups; untreated control group (group I), sham control (group II), group with induced hypercholesterolaemia (group III), group with induced hypercholesterolaemia treated with selenium 0.25 mg/kg/day (group IV). RESULTS: Histological and ultrastructural examination of the epididymal epithelial cells of hypercholesterolaemic rats (group III) showed loss of cilia with many vacuolations, fatty degenerative changes and increased collagen fibres. Morphometrically significant increase (p < 0.0001) in the per cent area of collagen fibres with no significant change in the optical density of periodic acid Schiff reaction (p > 0.05). Selenium treated group (group IV) produced marked improvement in histological, ultrastructural and morphometric results as compared with group III. CONCLUSIONS: It could be concluded that hypercholesterolaemia produced deleterious effects to the epididymis and selenium could attenuate these effects.