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Aim of the study: Hepatocyte transplantation has been discussed as an alternative to liver transplantation in selected cases of acute and chronic liver failure and metabolic diseases. Immediately after infusion of hepatocytes, hypoxia-related cell injury is inevitable. N-acetylcysteine (NAC) has been suggested to attenuate hypoxic damage. This study’s objective was to evaluate NAC’s protective effect in a model of hypoxia-related hepatocyte injury. Material and methods: HepG2 cells were used as a model for hepatocytes and were cultured under standardized hypoxia or normoxia for 24 hours with or without NAC. Growth kinetics were monitored using trypan blue staining. The activation of apoptotic pathways was measured using quantitative real-time PCR for Bcl-2/Bax and p53. The proportions of vital, apoptotic and necrotic cells were verified by fluorescence activated cell sorting using annexin V-labelling. The expression of hypoxia inducible factor 1 (HIF-1) was measured indirectly using its downstream target vascular endothelial growth factor A (VEGF-A). Results: After NAC, cell proliferation increased under both hypoxia and normoxia by 528% and 320% (p < 0.05), while VEGF-A expression decreased under normoxia by 67% and 37% (p < 0.05). Compared to cells treated without NAC under hypoxia, the Bcl-2/Bax ratio increased significantly in cells treated with NAC. This finding was confirmed by an increased number of vital cells in FACS analysis. Conclusions: NAC protects hepatocytes from hypoxic injury and ultimately activates anti-apoptotic pathways.

Background: Although animal studies models are frequently used for the purpose of attenuating ischemia reperfusion injury (IRI) in liver transplantation (LT), many of pharmacological agents have not become part of clinical routine. Methods: A search was performed using the PubMed database to identify agents, from which 58 articles containing 2700 rat LT procedures were selected. The identified pharmacological agents were categorized as follows: I - adenosine agonists, nitric oxide agonists, endothelin antagonists, and prostaglandins, II - Kupffer cell inactivator, III - complement inhibiter, IV - antioxidant, V - neutrophil inactivator, VI -anti-apoptosis agent, VII - heat shock protein and nuclear factor kappa B inducer, VIII - metabolic agent, IX - traditional Chinese medicine, and X - others. Meta-analysis using 7-day-survival rate was also performed with Mantel-Haenszel's Random effects model. Results: The categorization revealed that the rate of donor-treated experiments in each group was highest for agents from Group II (70%) and VII (71%), whereas it was higher for agents from Group V (83%) in the recipient-treated experiments. Furthermore, 90% of the experiments with agents in Group II provided 7-day-survival benefits. The Risk Ratio (RR) of the metaanalysis was 2.43 [95% CI: 1.88-3.14] with moderate heterogeneity. However, the RR of each of the studies was too model-dependent to be used in the search for the most promising pharmacological agent. Conclusion: With regard to hepatic IRI pathology, the categorization of agents of interest would be a first step in designing suitable multifactorial and pleiotropic approaches to develop pharmacological strategies.

Zdigitalizowano z mikrofilmu

Zdigitalizowano z mikrofilmu

Zdigitalizowano z mikrofilmu

Zdigitalizowano z mikrofilmu

Zdigitalizowano z mikrofilmu

Zdigitalizowano z mikrofilmu

Zdigitalizowano z mikrofilmu

Def.: dekomplet; część panegiryku poświęconego Joachimowi Schnobelowi (skł. A4-B2), Zdigitalizowano z mikrofilmu

Współopr. rękopisy: 1. [Życiorys? J. Schnobella], podpisany: A. F. Taddel, 1766. 2. [Zagadnienia dot. genealogii niemieckiej], 1778, Zdigitalizowano z mikrofilmu

Zdigitalizowano z mikrofilmu

Def.: dekomplet, zachowała się tylko skł. J4, Zdigitalizowano z mikrofilmu