Bilirubin Exerts Protective Effects on Alveolar Type II Pneumocytes in an In Vitro Model of Oxidative Stress

• Published in: International journal of molecular sciences Vol. 25; no. 10; p. 5323
• Main Authors: Endesfelder, Stefanie, Schmitz, Thomas, Bührer, Christoph
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.05.2024
• Subjects: Alveolar Epithelial Cells - drug effects; Alveolar Epithelial Cells - metabolism; alveolar epithelial cells type II; Animals; Antioxidants; Antioxidants - pharmacology; Apoptosis - drug effects; Bilirubin; Bilirubin - metabolism; Bilirubin - pharmacology; Cell death; Cell Survival - drug effects; Cells, Cultured; Comparative analysis; DNA binding proteins; Free radicals (Chemistry); Genes; Genetic transcription; Homeostasis; Hyperoxia; Hypoxia; Infants (Newborn); Newborn babies; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; Oxidative stress; Oxidative Stress - drug effects; Physiology; Premature babies; Premature birth; Rats; Respiratory distress syndrome; Signal Transduction - drug effects; Transcription factors; Germany; alveolar epithelial cells type II; bilirubin; hypoxia; hyperoxia; oxidative stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25105323

Newborn infants face a rapid surge of oxygen and a more protracted rise of unconjugated bilirubin after birth. Bilirubin has a strong antioxidant capacity by scavenging free radicals, but it also exerts direct toxicity. This study investigates whether cultured rat alveolar epithelial cells type II (AEC II) react differently to bilirubin under different oxygen concentrations. The toxic threshold concentration of bilirubin was narrowed down by means of a cell viability test. Subsequent analyses of bilirubin effects under 5% oxygen and 80% oxygen compared to 21% oxygen, as well as pretreatment with bilirubin after 4 h and 24 h of incubation, were performed to determine the induction of apoptosis and the gene expression of associated transcripts of cell death, proliferation, and redox-sensitive transcription factors. Oxidative stress led to an increased rate of cell death and induced transcripts of redox-sensitive signaling pathways. At a non-cytotoxic concentration of 400 nm, bilirubin attenuated oxidative stress-induced responses and possibly mediated cellular antioxidant defense by influencing Nrf2/Hif1α- and NFκB-mediated signaling pathways. In conclusion, the study demonstrates that rat AEC II cells are protected from oxidative stress-induced impairment by low-dose bilirubin.