钼、镉联合暴露介导氧化应激和铁死亡致绵羊肾损伤

doi:10.11843/j.issn.0366-6964.2024.12.042

Abstract

Abstract:

The aim of this study was to investigate the role of oxidative stress and ferroptosis in renal tissue injury caused by molybdenum, cadmium and their combined exposure in sheep. Twenty-four sheep aged 2 months were randomly divided into 4 groups, namely control group (Control), molybdenum group (Mo), cadmium group (Cd) and molybdenum cadmium combined group (Mo+Cd). The control group was given equal volume of distilled water, the Mo group was given 45 mg Mo·kg^-1BW, group Cd was given 1 mg Cd·kg^-1BW, and group Mo+Cd was given 1 mg Cd+45 mg Mo·kg^-1BW. The experimental period lasted for 75 d. At the end of the experiment, serum and kidney tissue were collected, pathological and ultrapathological changes of sheep kidney were observed, and the levels of serum renal function indexes, renal tissue oxidative stress and ferroptosis related factors were detected. The results showed that molybdenum, cadmium and their combined exposure increased the levels of serum renal function indicators (creatinine, urea and uric acid). In the Mo, Cd, and Mo+Cd groups, the renal tubular epithelial cells underwent degeneration, manifesting as swelling, structural blurring, and lysis. The cytoplasm contained minute red granules and vacuoles, indicating granular degeneration, vacuolar degeneration, and necrosis. Additionally, the renal tubular lumens were observed to contain pink-stained filamentous components, while the number of red blood cells was elevated in some glomeruli and interstitial spaces. The results of transmission electron microscopy showed that molybdenum, cadmium and their combined exposure resulted in the reduction of mitochondrial volume, blurring of ridge and vacuolation in renal tubular epithelial cells. The contents of oxidative damage related factors (H₂O₂, MDA) and Fe ions, the mRNA expression levels of ferroptosis related factors (NCOA4, ACSL4, TFR1 and PTGS2) and the protein expression levels of PTGS2 were increased in Mo and Cd groups. The mRNA and protein expression levels of antioxidant related factors (GSH, CAT and GSH-Px) and ferroptosis related factors (SLC7A11, GPX4 and FTH1) were decreased, and the above changes were more obvious in Mo+Cd group. Pearson correlation analysis showed that the levels of oxidative damage related factors (H₂O₂, MDA) and Fe ions were positively correlated with the expression levels of ferroptosis related factors (NCOA4, ACSL4, TFR1 and PTGS2), and negatively correlated with the expression levels of ferroptosis related factors (SLC7A11, GPX4 and FTH1). The correlation of antioxidant related factors (GSH, CAT and GSH-Px) and ferroptosis related factors was opposite to that of oxidative damage related factors. This study shows that molybdenum cadmium and its combined exposure induced renal oxidative stress and ferroptosis in sheep, resulting in renal tissue damage, and molybdenum, cadmium toxicity has a synergistic effect.

Key words: sheep, molybdenum, cadmium, oxidative stress, ferroptosis

CLC Number:

S856.9

XIONG Zhiwei, WANG Yun, CAO Huabin, PENG Chengcheng, YANG Fan, DAI Xueyan, XING Chenghong, LIU Lingli, LI Jingni, HU Aiming. Molybdenum and Cadmium Combined Exposure Mediates Oxidative Stress and Ferroptosis Induced Kidney Damage in Sheep[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(12): 5802-5812.

Figures/Tables 7

Table 1

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References 30

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基因 Gene	登录号 Accession number	上游引物(F)	下游引物(R)
NCOA4	XM_060406763.1	TTCAGAGCAGTCATTGCGGT	ACAATGGCAAACGTGGCATC
ACSL4	XM_042242179.1	CTCATGGGGTCGCAAAGAGT	GACAGTAGACGTTGGAAGTTGC
TFR1	XM_054347664.1	TCAGGTCAAAGGCAGTTCTCAA	TAGCATGGACCAGTTTGCCA
PTGS2	NM_001009432	CATGGGTGTGAAAGGGAGGAA	TCCCTTGGTGAAAGCTGGTC
SLC7A11	NM_001252182.1	GCAGGGCAGTGTTAATGGGAG	GCACGCCCTTAGGAGAGAT
GPX4	XM_060416444.1	GTTCGCTGCTGGCTATAACG	TCCATTTGATGGCGTTTCCC
FTH1	XM_060403847.1	TGACCGTGATGATGTGGCTTT	GCACAGCGCACATTCCATTG
GAPDH	XM_060411595.1	AGAGTGAGTGTCGCTGTTGAAGT	TCCGTTGTGGATCTGACCTG

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Molybdenum and Cadmium Combined Exposure Mediates Oxidative Stress and Ferroptosis Induced Kidney Damage in Sheep

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