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Combination treatment of zinc and selenium intervention ameliorated BPA-exposed germ cell damage in SD rats: elucidation of molecular mechanisms

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Abstract

Bisphenol A (BPA) is a commonly used environmental toxicant, is easily exposed to the human body and causes testicular damage, sperm abnormalities, DNA damage and apoptosis, and interferes in the process spermatogenesis and steroidal hormone production along with obstruction in testes and epididymis development. Zinc (Zn), a potent regulator of antioxidant balance, is responsible for cellular homeostasis, enzymes and proteins activities during spermatogenesis for cell defence mechanisms in the testes. Selenium (Se) is required for spermatogenesis, antioxidant action and in the activities of different selenoproteins. Both Zn and Se are essential simultaneously for the proper regulation of spermatogenesis and sperm maturation as well as protection against chemical and disease-associated germ cell toxicity. Thus, the study aimed to understand the importance and beneficial effect of Zn and Se co-treatment against BPA-exposed testicular damage in rats. BPA 100 and 200 mg/kg/day was exposed through an oral gavage. Zn (3 mg/kg/day) i.p. and Se (0.5 mg/kg/day) i.p. were injected for 8 weeks. The testicular toxicity was evaluated by measuring body and organs weight, biochemical investigations, sperm parameters, testicular and epididymal histopathology, quantification DNA damage by halo assay, DNA breaks (TUNEL assay), immunohistochemistry and western blot. Results revealed that Zn and Se co-treatment ameliorated BPA-associated male gonadal toxicity in rat as revealed by decreased SGPT, SGOT and BUN levels in serum, reduced testes and epididymis tissue injury, DNA breaks, apoptosis, expressions of 8-OHdG, γ-H2AX and NFκB with an increased serum testosterone and catalase levels. These findings suggest that Zn and Se co-treatment could be a beneficial and protective option against BPA-exposed testicular and epididymal toxicity.

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Data availability

The data and materials will be available on demand where ever applicable.

Abbreviations

BPA:

Bisphenol A

COX:

Cyclooxygenase

DMSO:

Dimethyl sulfoxide

DPX:

Dibutyl phthalate in xylene

ECL:

Enhanced chemiluminescence

Fas (Apo-1):

Apoptosis antigen 1

GD:

Gestation day

IKK:

I kappa B kinase

NDF:

Nuclear diffusion factor

NFκB:

Nuclear factor kappa B

PI3K:

Phosphatidylinositol triphosphate

PND:

Post-natal day

SGPT:

Serum glutamic-pyruvic transaminase (alanine aminotransferase)

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Acknowledgements

C. Sahu is thankful to UGC for providing research fellowship (ID: 328410).

Funding

The institutional financial assistance was received (budget allotment no. NPLC) by the NIPER, S.A.S. Nagar, India.

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Authors and Affiliations

  1. Facility for Risk Assessment and Intervention Studies, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S., Nagar, Punjab, 160062, India

    Chittaranjan Sahu & Gopabandhu Jena

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  1. Chittaranjan Sahu
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  2. Gopabandhu Jena
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Contributions

Chittaranjan Sahu conceived and conceptualize the study, performed the experiments, analyzed the data and wrote entire manuscript. G. B. Jena supervised research work and reviewed the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Gopabandhu Jena.

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The animal study plan was duly approved by Institutional Animal Ethics Committee (IAEC) of the National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, India with approval no. IAEC/19/46). Animal experiments were conducted according to CPCSEA (Govt. of India) guidelines.

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The authors declare no competing interests.

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Sahu, C., Jena, G. Combination treatment of zinc and selenium intervention ameliorated BPA-exposed germ cell damage in SD rats: elucidation of molecular mechanisms. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03044-4

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