Molybdenum and Cadmium Co-exposure Impairs Splenic Mitochondrial Homeostasis and Promotes Ferroptosis-Related Injury in Sheep.
- 1Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Economic and Technological Development District, Nanchang, Jiangxi, P. R. China.
- 2Fujian Vocational College of Agriculture, Fuqing, Fuzhou, Fujian, P. R. China.
- 3Department of Pharmacy, School of Medicine, Guangxi University of Science and Technology, Liuzhou, Guangxi, P. R. China.
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.
Related
- Restoring Endothelial Mitochondrial Homeostasis With a Bioactive Nanoshield Promotes Vascular Regeneration on Cardiovascular Implants
- Hypoxia-induced sulfide:quinone oxidoreductase suppresses ferroptosis and promotes gemcitabine resistance through mitochondrial coenzyme Q reduction in pancreatic ductal adenocarcinoma
- CDCA5 promotes hepatocellular carcinoma progression by suppressing ferroptosis through PP2Ac/p53/STEAP3 signaling
- SESN2 promotes ferroptosis in bladder cancer by negatively regulating the NRF2/FSP1 signaling axis
- MSRB3 promotes gastric cancer progression and immunotherapy resistance by stabilizing GPX4 to inhibit ferroptosis
BibTeX
@article{liu2026molybdenum,
title = {{Molybdenum and Cadmium Co-exposure Impairs Splenic Mitochondrial Homeostasis and Promotes Ferroptosis-Related Injury in Sheep.}},
author = {Lingli Liu and Xueyan Dai and Fan Yang and Chenghong Xing and Zhiwei Xiong and Feiyan Gao and Chengcheng Peng and Zhou Jiang and Kangyan Xu and Mingwen Hu and Haotang Li and Huabin Cao},
journal = {International journal of veterinary science and medicine},
year = {2026},
month = sep,
doi = {10.4103/ijvsm.ijvsm_42_26},
url = {https://europepmc.org/article/MED/42960379},
note = {CC BY-NC-SA},
}
RIS
TY - JOUR
TI - Molybdenum and Cadmium Co-exposure Impairs Splenic Mitochondrial Homeostasis and Promotes Ferroptosis-Related Injury in Sheep.
AU - Lingli Liu
AU - Xueyan Dai
AU - Fan Yang
AU - Chenghong Xing
AU - Zhiwei Xiong
AU - Feiyan Gao
AU - Chengcheng Peng
AU - Zhou Jiang
AU - Kangyan Xu
AU - Mingwen Hu
AU - Haotang Li
AU - Huabin Cao
PY - 2026
DA - 2026/09/29
JO - International journal of veterinary science and medicine
DO - 10.4103/ijvsm.ijvsm_42_26
UR - https://europepmc.org/article/MED/42960379
AB - 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.
SN - 2314-4580
SN - 2314-4599
ER -