Integrated Metabolomics and Proteomics Reveal Gender-Dependent Immunotoxicity Mechanisms of Mineral Oil Saturated Hydrocarbons in Fischer 344 Rats.

Bibliographic Details
Title:	Integrated Metabolomics and Proteomics Reveal Gender-Dependent Immunotoxicity Mechanisms of Mineral Oil Saturated Hydrocarbons in Fischer 344 Rats.
Authors:	Zhu L; Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China., Zhang M; Wilmar (Shanghai) Biotechnology Research & Development Center Co. Ltd., Shanghai 200137, China., Zhang H; Wilmar (Shanghai) Biotechnology Research & Development Center Co. Ltd., Shanghai 200137, China., Zhang H; Wilmar (Shanghai) Biotechnology Research & Development Center Co. Ltd., Shanghai 200137, China., Gao B; Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China., Yu LL; Department of Nutrition and Food Science, University of Maryland, College Park, Maryland 20742, United States., Zhang Y; Institute of Food and Nutraceutical Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Source:	Journal of agricultural and food chemistry [J Agric Food Chem] 2026 Mar 11; Vol. 74 (9), pp. 7976-7990. Date of Electronic Publication: 2026 Feb 27.
Publication Type:	Journal Article
Language:	English
Journal Info:	Publisher: American Chemical Society Country of Publication: United States NLM ID: 0374755 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5118 (Electronic) Linking ISSN: 00218561 NLM ISO Abbreviation: J Agric Food Chem Subsets: MEDLINE
Imprint Name(s):	Original Publication: Washington, American Chemical Society.
MeSH Terms:	Mineral Oil/toxicity , Mineral Oil/chemistry , Hydrocarbons*/toxicity, Spleen/drug effects ; Spleen/immunology ; Spleen/metabolism ; Animals ; Male ; Female ; Rats, Inbred F344 ; Rats ; Proteomics ; Metabolomics ; Sex Factors
Abstract:	A 6 month subchronic toxicity study demonstrated that exposure to the mineral oil saturated hydrocarbon (MOSH) subfraction (predominant carbon range C20-30) induced dose- and gender-dependent immunometabolic disruption in Fischer 344 rats. Both low- (1.5 g/kg) and high-dose (15 g/kg) exposure significantly reduced the arterial blood CD4⁺/CD8⁺ T-cell ratio in both genders (female: 1.85 ± 0.40 and 1.27 ± 0.13 vs 3.14 ± 0.20 in controls; male: 1.04 ± 0.39 and 0.95 ± 0.26 vs 4.38 ± 0.54 in controls), indicating concomitant immune dysregulation and inflammation. Integrated metabolomic and proteomic analyses of the spleen elucidated distinct gender-associated responses. Females exhibited upregulated purine metabolism, evidenced by elevated purine intermediates (5-aminoimidazole ribonucleotide and 5'-phosphoribosyl-N-formylglycinamide) and increased expression of proteins involved in de novo synthesis (PRPS1, GART, and ADSS2) and salvage pathways (adenylate kinase 3, guanine deaminase, and GMPR). In contrast, males displayed a dual pathophysiological pattern characterized by systemic purine activation alongside suppressed mitochondrial energy metabolism (PDHB, HK1, and ACSS1), impaired glutathione homeostasis (GSR and GSTA4), and downregulated heme metabolism (ALAS2, HMBS, CPOX, FECH, HMOX1, and CP). These alterations were consistently more pronounced in the high-dose group. The findings reveal gender-specific immunometabolic toxicity of the MOSH C20-30 subfraction, highlighting the necessity of incorporating gender-specific effects and immunometabolic endpoints in future risk assessment of MOSH exposure.
Contributed Indexing:	Keywords: gender-dependent; immunotoxicity; mineral oil saturated hydrocarbon (MOSH) subfraction; multiomics integration; spleen
Substance Nomenclature:	8020-83-5 (Mineral Oil) 0 (Hydrocarbons)
Entry Date(s):	Date Created: 20260227 Date Completed: 20260709 Latest Revision: 20260709
Update Code:	20260711
DOI:	10.1021/acs.jafc.5c15401
PMID:	41758903
Database:	MEDLINE

Description
ISSN:	1520-5118
DOI:	10.1021/acs.jafc.5c15401