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Protective effect of iron against cadmium-induced lesions in rat testis via downregulation of NQO1/Nrf2 and NF-κB
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  • Published: 16 March 2026

Protective effect of iron against cadmium-induced lesions in rat testis via downregulation of NQO1/Nrf2 and NF-κB

  • Oluwagbenga J. Ogunbiyi  ORCID: orcid.org/0000-0002-7583-22961,2,
  • Ngozi P. Okolie  ORCID: orcid.org/0000-0001-8558-76881,
  • Frederick O. Obi  ORCID: orcid.org/0000-0002-2230-19693,
  • Olusola O. Elekofehinti  ORCID: orcid.org/0000-0002-7921-70474 &
  • …
  • Victor O. Ukwenya  ORCID: orcid.org/0000-0002-8772-55785 

Scientific Reports , Article number:  (2026) Cite this article

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Subjects

  • Biochemistry
  • Cell biology
  • Environmental sciences
  • Molecular biology
  • Physiology

Abstract

At low concentrations, cadmium (Cd) stimulates expression of cytoprotective genes. Cadmium induces the mRNA of NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), which are nuclear factor (erythroid-derived 2)-like (Nrf2) transcription enzymes. Hence, the current study was designed to evaluate the probable protective role of iron (Fe) on Cd toxicity on the gonads of male rats. Twenty adult male albino rats were divided into four groups. The groups were designated as group A-control (rats exposed to exogenous Cd- and Fe-free water), group B (rats exposed to Cd-tainted water), group C (rats exposed to Fe-tainted water) and group D (rats exposed to Cd and Fe-tainted water concomitantly). The rats were initially gavaged with 0.229 mg/L Cd and 1.900 mg/L Fe tainted water, and the remaining solution was provided as drinking for the 4-week duration. Biochemical assays, hormone profiling, gene expression analysis, and histopathological evaluations were conducted on serum, plasma and testicular tissues. The study reveals that Cd induces oxidative stress, evidenced by decreased catalase (CAT) activities, whereas iron exposure showed antioxidant effects with alterations in malondialdehyde (MDA) levels. Concomitant exposure to Cd + Fe shows a reversal in the CAT activity in the serum of Cd-exposed rats. The levels of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) were significantly increased (p ≤ 0.05) in the plasma of rats exposed to Cd and Cd + Fe relative to the control. The testosterone and estradiol levels were significantly modulated in the plasma of rats exposed to Cd and Cd + Fe relative to the control. Exposure of rats to Cd only and Cd + Fe significantly downregulated HO-1 relative to the control. The mRNA level of NQO1 was significantly upregulated in the Cd only group relative to the control, but downregulated in the Cd + Fe group. The levels of Nrf2 and nuclear transcription factor kappa B (NF-κB) were upregulated in Cd only but downregulated in the Cd + Fe group relative to the control. Cadmium-induced alteration in mRNA levels in NQO1, Nrf2 and NF-κB was reversed in the presence of Fe. Histological changes in the testis of Cd-intoxicated rats were ameliorated in the presence of Fe. In conclusion, iron has the potential to offer protection against Cd-induced lesions in rat testis via a mechanism involving downregulation of NQO1/Nrf2 and NF-κB.

Data availability

The datasets generated and/or analysed during the current study are available on reasonable request from the corresponding author.

Abbreviations

NQO1:

NAD(P)H: quinone oxidoreductase 1

HO-1:

Heme oxygenase-1

Nrf2:

Nuclear factor (erythroid-derived 2)-like factor-2

NF-κB:

Nuclear transcription factor kappa B

CAT:

Catalase

MDA:

Malondialdehyde

GSH:

Reduced glutathione

SOD:

Superoxide dismutase

LH:

Luteinizing Hormone

FSH:

Follicle-Stimulating Hormone

WT:

Wild type

MEF:

Mouse Embryonic Fibroblasts

ROS:

Reactive oxygen species

DMT1:

Divalent metal transporter-1

MTP1:

Metal transporter protein 1

ELISA:

Enzyme-linked immunosorbent assay

RNA:

Ribonucleic acid

DNA:

Deoxyribonucleic acid

cDNA:

Complementary Deoxyribonucleic acid

PCR:

Polymerase chain reaction

TRFC:

Transferrin receptor protein 1

EPO:

Erythropoietin

GAPDH:

Glycerol aldehyde phosphate dehydrogenase

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Acknowledgements

The authors are grateful for the support received from the Petroleum Technology Development Fund (PTDF) with Ref No. PTDF/ED/ISS/PHD/OJO/1947/21.

We wish to acknowledge the support received from the management of Teady Bioscience Research Laboratory, Akure. Special thanks to Dr Akpeh Kingsley in the Biochemistry Department at the University of Benin for his assistance and support during this research.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Life Sciences, University of Benin, Benin City, Nigeria

    Oluwagbenga J. Ogunbiyi & Ngozi P. Okolie

  2. Biology Unit, Faculty of Science, Air Force Institute of Technology, Kaduna, Nigeria

    Oluwagbenga J. Ogunbiyi

  3. Department of Biochemistry, Michael and Cecilia Ibru University, Agbarha- Otor, Ughelli, Nigeria

    Frederick O. Obi

  4. Department of Biochemistry, School of Life Sciences, Federal University of Technology, Akure, Nigeria

    Olusola O. Elekofehinti

  5. Department of Human Anatomy, School of Basic Medical Sciences, Federal University of Technology, Akure, Nigeria

    Victor O. Ukwenya

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Contributions

OOJ conceived the idea for this research and proposed the research design. OOJ and ONP supervised the research and were major contributors to writing the original manuscript. OOJ, EOO, and OFO conducted the experiment, analysed, and interpreted the research data. UVO performed the histological examination of the testes and interpreted the results. OOJ and ONP conducted a critical review of the revised manuscript and were major contributors to its editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Oluwagbenga J. Ogunbiyi.

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Competing interests

The authors declare no competing interests.

Ethical approval

Ethical approval for the use of laboratory animals was obtained from the Faculty of Life Science Research Ethics Committee (FLSREC) of the University of Benin, with approval number FLSREC-2023-007.

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Ogunbiyi, O.J., Okolie, N.P., Obi, F.O. et al. Protective effect of iron against cadmium-induced lesions in rat testis via downregulation of NQO1/Nrf2 and NF-κB. Sci Rep (2026). https://doi.org/10.1038/s41598-026-43876-z

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  • Received: 02 December 2025

  • Accepted: 06 March 2026

  • Published: 16 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-43876-z

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Keywords

  • Gene expression
  • mRNA
  • gonad
  • hormone
  • exposure
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