{"doi":"10.1093/toxres/tfaf104","title":"Hormetic association between sodium nitrate and liver enzymes: a study in female and male rats","abstract":"This study aims to evaluate the long-term dose-dependent effects of sodium nitrate on serum ALT, AST, and ALP in healthy female and male rats. A total of 120 rats (60 females and 60 males) were divided into 6 subgroups (n = 10). In each sex, a control group received regular tap water, while five treatment groups received sodium nitrate in tap water (50, 100, 150, 250, and 500 mg/L). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and nitric oxide (NO) metabolites (NOx) were measured at baseline (month 0) and after 6 mo. Hormetic zones for sodium nitrate in female rats were 10-230 mg/L for ALT, 20-180 mg/L for AST, and 8-270 mg/L for ALP. In males, the zones were 5-190 mg/L for ALT, 7-180 mg/L for AST, and 7-265 mg/L for ALP. Serum NOx levels were negatively correlated with ALT (r = -0.498) and AST (r = -0.320) at moderate doses (100-150 mg/dL) but positively correlated with ALT (r = 0.500) and AST (r = 0.300) at higher doses (250-500 mg/dL (all P < 0.05). Sodium nitrate exhibited a J-shaped dose-response relationship with liver function tests (LFTs) in both female and male rats. Protective effects were observed at moderate doses (100 mg/L for ALT and AST; 150 mg/L for ALP), while low doses (<10 mg/L) were ineffective, and high doses (>200 mg/L for ALT/AST; >250 mg/L for ALP) were toxic. These findings highlight the dual potential of sodium nitrate as both beneficial and harmful, depending on the dosage in healthy state.","journal":"Toxicology Research","year":2025,"id":571020,"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":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"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":1258583,"name":"Sajad Jeddi","orcid":"0000-0002-3911-6620","position":1,"is_corresponding":false},{"id":38055,"name":"Khosrow Kashfi","orcid":"0000-0002-4060-7283","position":2,"is_corresponding":false},{"id":38053,"name":"Asghar Ghasemi","orcid":"0000-0001-6867-2151","position":3,"is_corresponding":false},{"id":1476450,"name":"Ramin Zeinodini","orcid":"0009-0005-6523-7257","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:57:11.713851Z","pmid":"40726758","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":[]}