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Molybdenum and Cadmium Co-exposure Impairs Splenic Mitochondrial Homeostasis and Promotes Ferroptosis-Related Injury in Sheep.

Year: 2026

Type: article

Abstract: Background: Molybdenum (Mo) and cadmium (Cd) can contaminate feed, water, and agricultural environments, thereby threatening food-producing animals. However, their combined effects on splenic mitochondrial homeostasis in ruminants remain unclear. Aims and Objectives: This study aimed to investigate the effects of Mo and Cd, individually and in combination, on splenic injury, mitochondrial homeostasis, mitophagy-related markers, and ferroptosis-related alterations in sheep. Materials and Methods: Seventy-two 2-month-old lambs were randomly assigned to four groups: control, Mo, Cd, and Mo + Cd groups, and were orally administered 45 mg Mo•kg⁻¹ body weight and/or 1 mg Cd•kg⁻¹ body weight daily for 75 days. Splenic morphology, oxidative stress, iron metabolism, mitochondrial ultrastructure and dynamics, mitophagy-related markers, TBK1-OPTN-related signaling, and ferroptosis-related indices were evaluated. Results: Mo and/or Cd exposure induced splenic morphological alterations, including disorganized tissue architecture, indistinct red-white pulp boundaries, and thickening of the central arteriole wall. These changes were accompanied by decreased glutathione content and catalase activity and increased malondialdehyde, H₂O₂, 4-HNE, and Fe²⁺ levels. Transmission electron microscopy revealed mitochondrial cristae disruption, vacuolization, and shrinkage. GPX4, FTH1, and SLC7A11 expression decreased, whereas NCOA4 expression increased. Mo and Cd exposure also altered mitochondrial dynamics, increased PINK1, Parkin, and LC3B expression, reduced p62 expression, and enhanced PINK1-Parkin colocalization. Increased TBK1 phosphorylation, OPTN expression, and NCOA4-LC3B colocalization were also observed. Conclusion: Mo and Cd co-exposure impaired splenic mitochondrial homeostasis and was associated with coordinated mitophagy- and ferroptosis-related alterations in sheep.

Source: PubMed

DOI: 10.4103/ijvsm.ijvsm_42_26