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Response of the nuclear xenobiotic receptors to alleviate glyphosate-based herbicide-induced nephrotoxicity in weaned piglets

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Abstract

Glyphosate-based herbicides (GBHs) are widely used worldwide. Glyphosate (GLP) is the main active component of GBHs. The presence of GBH residues in the environment has led to the exposure of animals to GBHs, but the mechanisms of GBH-induced nephrotoxicity are not clear. This study investigated the effects of GBHs on piglet kidneys. Twenty-eight healthy female hybrid weaned piglets (Duroc × Landrace × Yorkshire) with an average weight of 12.24 ± 0.61 kg were randomly divided into four treatment groups (n=7 piglets/group) that were supplemented with Roundup® (equivalent to GLP concentrations of 0, 10, 20, and 40 mg/kg) for a 35-day feeding trial. The results showed that the kidneys in the 40-mg/kg GLP group suffered slight damage. Roundup® significantly decreased the activity of catalase (CAT) (P=0.005) and increased the activity of superoxide dismutase (SOD) (P=0.029). Roundup® increased the level of cystatin-C (Cys-C) in the plasma (linear, P=0.002 and quadratic, P=0.015). The levels of neutrophil gelatinase–associated lipocalin (NGAL) in plasma increased linearly (P=0.007) and quadratically (P=0.003) as the dose of GLP increased. The mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1) in the 20-mg/kg GLP group was increased significantly (P<0.05). There was a significant increase in the mRNA levels of pregnenolone X receptor (PXR), constitutive androstane receptor (CAR), and uridine diphosphate glucuronosyltransferase 1A3 (UGT1A3) (P<0.05). Our findings found that kidney nuclear xenobiotic receptors (NXRs) may play an important role in defense against GBHs.

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Abbreviations

GBHs:

Glyphosate-based herbicides

GLP:

Glyphosate

GLP10:

Glyphosate 10 mg/kg

GLP20:

Glyphosate 20 mg/kg

GLP40:

Glyphosate 40 mg/kg

SOD:

Superoxide dismutase

CAT:

Catalase

GSH-Px/GPx:

Glutathione peroxidase

MDA:

Methane dicarboxylic aldehyde

Cys-C:

Cystatin-C

NGAL:

Neutrophil gelatinase–associated lipocalin

MCP-1:

Monocyte chemoattractant protein-1

ICAM-1:

Intercellular cell adhesion molecule-1

TNF-α:

Tumor necrosis factor α

IL-6:

Interleukin-6

IL-8:

Interleukin-8

CAR:

Constitutive androstane receptor

PXR:

Pregnenolone X receptor

CYP1A1:

Cytochrome P450 1A1

CYP1A2:

Cytochrome P450 1A2

CYP2E1:

Cytochrome P450 2E1

UGT1A3:

Uridine diphosphate glucuronosyltransferase 1A3

UGT1A6:

Uridine diphosphate glucuronosyltransferase 1A6

GSTA1:

Glutathione S-transferase A1

GSTA2:

Glutathione S-transferase A1

MDR1:

Multidrug resistance-1

NXRs:

Nuclear xenobiotic receptors

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Acknowledgements

The authors thank all the participants and staff of this trial for their valuable contributions.

Funding

This work was supported by the Provincial Science Fund for Distinguished Young Scholars (JQ2019C002).

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Authors and Affiliations

  1. Institute of Animal Nutrition, Northeast Agricultural University, Harbin, 150030, People’s Republic of China

    Shengnan Qiu, Yang Liu, Yanan Gao, Huiyang Fu & Baoming Shi

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  1. Shengnan Qiu
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Contributions

SNQ performed the experiments, statistical data analysis, and writing original draft. YL, YNG, and HYF performed writing, review, and editing. BMS supervised the research and acquired the financial support. All authors provided major input on the manuscript.

Corresponding author

Correspondence to Baoming Shi.

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Ethics approval

The experimental proposals and procedures for the care and treatment of the pigs were approved by the Animal Care and Use Committee of Northeast Agricultural University and followed Chinese Guidelines for Animal Welfare (NEAU-[2011]-9).

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Highlights

1. GLP (10–40 mg/kg) did not cause oxidative stress in the kidneys of piglets.

2. GLP caused kidney damage, as shown by the increase in pNGAL and pCys-C.

3. The upregulated mRNA expression of ICAM-1 indicated GLP-induced inflammation.

4. The nuclear receptor may play an important role in the defense against GLP.

5. This is the first report of adverse effects of GLP on piglet kidneys.

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Qiu, S., Liu, Y., Gao, Y. et al. Response of the nuclear xenobiotic receptors to alleviate glyphosate-based herbicide-induced nephrotoxicity in weaned piglets. Environ Sci Pollut Res 29, 2707–2717 (2022). https://doi.org/10.1007/s11356-021-15831-0

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