{"doi":"10.1093/pnasnexus/pgac191","title":"Cobinamide is a strong and versatile antioxidant that overcomes oxidative stress in cells, flies, and diabetic mice","abstract":"Abstract Increased oxidative stress underlies a variety of diseases, including diabetes. Here, we show that the cobalamin/vitamin B12 analog cobinamide is a strong and multifaceted antioxidant, neutralizing superoxide, hydrogen peroxide, and peroxynitrite, with apparent rate constants of 1.9 × 108, 3.7 × 104, and 6.3 × 106 M−1 s−1, respectively, for cobinamide with the cobalt in the +2 oxidation state. Cobinamide with the cobalt in the +3 oxidation state yielded apparent rate constants of 1.1 × 108 and 8.0 × 102 M−1 s−1 for superoxide and hydrogen peroxide, respectively. In mammalian cells and Drosophila melanogaster, cobinamide outperformed cobalamin and two well-known antioxidants, imisopasem manganese and manganese(III)tetrakis(4-benzoic acid)porphyrin, in reducing oxidative stress as evidenced by: (i) decreased mitochondrial superoxide and return of the mitochondrial membrane potential in rotenone- and antimycin A-exposed H9c2 rat cardiomyocytes; (ii) reduced JNK phosphorylation in hydrogen-peroxide-treated H9c2 cells; (iii) increased growth in paraquat-exposed COS-7 fibroblasts; and (iv) improved survival in paraquat-treated flies. In diabetic mice, cobinamide administered in the animals’ drinking water completely prevented an increase in lipid and protein oxidation, DNA damage, and fibrosis in the heart. Cobinamide is a promising new antioxidant that has potential use in diseases with heightened oxidative stress.","journal":"PNAS Nexus","year":2022,"id":245844,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":437032,"name":"John Tat","orcid":null,"position":1,"is_corresponding":false},{"id":881041,"name":"Shyamsundar Pal China","orcid":"0000-0003-0062-3593","position":2,"is_corresponding":false},{"id":374129,"name":"Hema Kalyanaraman","orcid":"0000-0003-4870-937X","position":3,"is_corresponding":false},{"id":375319,"name":"Shunhui Zhuang","orcid":null,"position":4,"is_corresponding":false},{"id":375320,"name":"Adriano Chan","orcid":null,"position":5,"is_corresponding":false},{"id":881514,"name":"Cassandra Lai","orcid":null,"position":6,"is_corresponding":false},{"id":732168,"name":"Zoran Radić","orcid":"0000-0003-0806-3869","position":7,"is_corresponding":false},{"id":667391,"name":"Engy A. Abdel‐Rahman","orcid":null,"position":8,"is_corresponding":false},{"id":374128,"name":"Darren E. Casteel","orcid":"0000-0002-7673-6597","position":9,"is_corresponding":false},{"id":374130,"name":"Renate B. Pilz","orcid":"0000-0003-4555-3541","position":10,"is_corresponding":false},{"id":666818,"name":"Sameh S. Ali","orcid":"0000-0002-0339-6106","position":11,"is_corresponding":false},{"id":374131,"name":"Gerry R. Boss","orcid":"0000-0002-9758-8714","position":12,"is_corresponding":false},{"id":881513,"name":"Stephen C. Chang","orcid":null,"position":0,"is_corresponding":true}],"reference_count":77,"raw_metadata":null,"created_at":"2026-07-19T00:23:39.284121Z","pmid":"36276587","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":[]}