Transkriptionsfaktorn NF-κB’s roll vid läkemedelsinducerad leverskada
Josefin Söderbaum Lindberg
Fördjupningsprojekt 15 hp, Receptarieprogrammet
Institutionen för Farmaceutisk Biovetenskap
Maria Norlin
Background: This study is about a drug adverse event and the most common reason for canceled drug development, Drug induced liver injury (DILI). Our immune system has a lot of factors but this systematic review will focus on NF-κB that induces transcription of factors related to inflammation, for example cytokines, anti-apoptosis and cell-proliferation.
Aim: The aim is to investigate if the transcription factor NF-κB has a protective role regarding DILI.
Methods: Five articles from PubMed were used to write a literature study. Inclusions: from 2012, free full text, not review and cell or animal studies. There was only one search including two keywords, “nf kappab AND DILI”.
Results: First up is an in vitro study (Wink et al, 2018) that severe-DILI drugs downregulated NF-κB. Next was in silico and in vitro (Herpers et al, 2015) with compound clusters and those that caused severe-DILI downregulated NF-κB and live cell imaging showed that induced NRF2 resulted in a negative regulation of NF-κB. The third was in silico (T. M. Souza, 2017) and showed with statistics that both DILI and non-DILI/carcinogenic drugs downregulated NF-κB. The fourth study (Alegre et al. 2022) showed that NF-kB’s expressed molecule SERPINE1 can cause liver fibrosis. The fifth study (Hassan et al from, 2020) resulted in less severe DILI when Ganoderma lucidum mushrooms suppressed NF-kB.
Conclusion: The conclusion is that NF-κB may have a protective role in some situations, since it is anti-apoptotic and can stimulate proliferation. Unfortunately, since it is hard to regulate NF-κB may harm the liver.
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