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Published on: October 19, 2013
Postnatal hyperoxia exposure differentially affects hepatocytes and liver haemopoietic cells in newborn rats
Guya Diletta Marconi1, Susi Zara1, Marianna De Colli1
1Department of Pharmacy, University "G. d'Annunzio" Chieti-Pescara, Chieti, Italy.
Insights
Premature newborns exposed to oxygen therapy experience distinct liver changes. Severe hyperoxia impacts liver cells and blood cell development, suggesting differential effects of oxygen on liver tissue.
Area of Science:
- Neonatal physiology
- Liver biology
- Oxygen toxicity
Background:
- Premature infants often require oxygen therapy, leading to hyperoxia.
- Hyperoxia's effects on liver metabolism are known, but its impact on growth factors, signaling molecules, and liver blood cell development is unclear.
- Understanding hyperoxia's influence on liver tissue is crucial for neonatal care.
Purpose of the Study:
- To investigate the effects of varying hyperoxia levels on liver tissue in newborn rats.
- To analyze changes in key proteins: Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1α (HIF-1α), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB).
- To differentiate hyperoxia's impact on liver cells (hepatocytes) and blood-forming cells (haemopoietic cells).
Main Methods:
- Newborn rats were exposed to room air, moderate (60% O2), or severe (95% O2) hyperoxia for two weeks.
- Immunohistochemistry and Western blot techniques were used for analysis.
- Evaluated changes in hepatocytes, haemopoietic cells, and specific protein expressions.
Main Results:
- Severe hyperoxia increased hepatocyte apoptosis and MMP-9, while decreasing VEGF.
- Moderate and severe hyperoxia reduced reticular fibers in the liver.
- Hyperoxia differentially affected hepatocytes (e.g., HIF-1α, eNOS, NF-kB changes) and haemopoietic cells (increased haemopoiesis, altered VEGF and eNOS expression).
Conclusions:
- Hyperoxia exerts distinct effects on hepatocytes and haemopoietic cells within the liver.
- VEGF and eNOS are likely involved in the liver's blood cell response to hyperoxia.
- Findings highlight the complex role of oxygen levels in neonatal liver development and function.
Abstract:
Premature newborns are frequently exposed to hyperoxic conditions and experimental data indicate modulation of liver metabolism by hyperoxia in the first postnatal period. Conversely, nothing is known about possible modulation of growth factors and signaling molecules involved in other hyperoxic responses and no data are available about the effects of hyperoxia in postnatal liver haematopoiesis. The aim of the study was to analyse the effects of hyperoxia in the liver tissue (hepatocytes and haemopoietic cells) and to investigate possible changes in the expression of Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase 9 (MMP-9), Hypoxia-Inducible Factor-1α (HIF-1α), endothelial Nitric Oxide Synthase (eNOS), and Nuclear Factor-kB (NF-kB). Experimental design of the study involved exposure of newborn rats to room air (controls), 60% O2 (moderate hyperoxia), or 95% O2 (severe hyperoxia) for the first two postnatal weeks. Immunohistochemical and Western blot analyses were performed. Severe hyperoxia increased hepatocyte apoptosis and MMP-9 expression and decreased VEGF expression. Reduced content in reticular fibers was found in moderate and severe hyperoxia. Some other changes were specifically produced in hepatocytes by moderate hyperoxia, i.e., upregulation of HIF-1α and downregulation of eNOS and NF-kB. Postnatal severe hyperoxia exposure increased liver haemopoiesis and upregulated the expression of VEGF (both moderate and severe hyperoxia) and eNOS (severe hyperoxia) in haemopoietic cells. In conclusion, our study showed different effects of hyperoxia on hepatocytes and haemopoietic cells and differential involvement of the above factors. The involvement of VEGF and eNOS in the liver haemopoietic response to hyperoxia may be hypothesized.
