{"doi":"10.36959/582/456","title":"RBT-1, A Pro-Oxidant Preconditioning Agent, Mitigates Syndecan-1 Shedding in Patients Undergoing Cardiac Surgery and Following Experimental AKI","abstract":"Background: During systemic stress, e.g., sepsis or major surgeries, syndecan-1 (SDC-1) shedding into plasma results, imply endothelial glycocalyx damage. A recent phase 2 clinical trial indicated that RBT-1 induced ‘oxidant preconditioning’ mitigated post-operative complications following cardiac surgeries. The present study assessed whether RBT-1 preconditioning attenuated SDC-1 shedding in these patients, implying a vascular protective effect. Methods: Patients (n, 112) were randomized to receive low-dose RBT-1, high-dose RBT-1, or placebo 24-48 hrs prior to surgery. Plasma samples were obtained before and 2 days post-surgery and assayed for SDC-1 (ELISA). The results were compared between the groups. To gain further insights, CD-1 mice were subjected to diverse forms of acute renal injuries (maleate, glycerol, endotoxemic AKI; acute heart failure). RBT-1’s impact on resulting plasma SDC-1 increases, vascular/aortic stress (NGAL/IL-6 gene induction), and the expression of two vascular cytoprotective pathways (Nrf2; ferritin) were assessed. Results: Baseline plasma SDC-1 levels did not differ between the three patient groups. The placebo group developed a 40 ± 11% post-surgical plasma SDC-1 increase (p, 0.03). Conversely, no significant SDC-1 increases (< 10%) were observed in the RBT-1 treatment groups (< RBT-1 vs. placebos, p, 0.015). Each form of experimental injury markedly increased plasma SDC concentrations. This result was attenuated by RBT-1 preconditioning. RBT-1 also: i) Mitigated injury-induced aortic NGAL/IL-6 mRNA increases; ii) Activated aortic Nrf2; and iii) Increased ferritin expression in aorta and select renal vessels. Conclusion: RBT-1 induced ‘oxidant preconditioning’ confers a vaso-protective effect, potentially by activating Nrf2 and up-regulating ferritin. Whether this can decrease post-cardiac surgery complications requires further study.","journal":"Journal of Cardiothoracic Surgery and Therapeutics","year":2025,"id":571844,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1405439,"name":"Richard A. Zager","orcid":"0000-0002-2067-2395","position":1,"is_corresponding":false},{"id":1406077,"name":"Ali C.M. Johnson","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:57:19.669553Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}