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Zinc Deficiency Exacerbates Bisphenol A–Induced Hepatic and Renal Damage: Delineation of Molecular Mechanisms

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Abstract

Zinc (Zn) plays an important role in the maintenance of redox status in the biological system. Zn deficiency has been found to be associated with negative effects on the functioning of many organ systems, including hepatic and renal systems. Bisphenol A (BPA) can alter Zn homeostasis and perturb the physiological system by provoking oxidative stress, which can lead to damage of different organs such as reproductive, immune, neuroendocrine, hepatic and renal systems. The present study aims to investigate the toxicity of BPA in Zn deficient condition in the liver and kidney of rat and to correlate its synergistic actions. Zn deficiency was induced by feeding Zn-deficient diet (ZDD), and BPA was administered orally (100 mg/kg/d). Male Sprague–Dawley rats were divided into four groups: NPD + Vehicle (normal feed and water), NPD + BPA (100 mg/kg/d), ZDD + Vehicle (fed with Zn-deficient diet only) and ZDD + BPA (Zn-deficient diet + BPA; 100 mg/kg/d) for 8 weeks. Biochemical, histopathological, TUNEL assay and protein expression profiles were determined to decipher the oxidative damage induced by ZDD and the toxicant BPA. Expression profile of nuclear factor erythroid 2-related factor 2, proliferating cell nuclear antigen, kelch-like ECH-associated protein 1, superoxide dismutase-1, metallothionein and apoptosis incidence showed that ZDD and BPA have a synergistic exacerbation effect on the liver and kidney of rat.

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All the data and materials support their published claims and comply with field standards. Data will be available on demand.

Abbreviations

BPA:

Bisphenol A

ZDD:

Zinc-deficient diet

NPD:

Normal pellet diet

Nrf2:

Nuclear factor erythroid 2-related factor 2

PCNA:

Proliferating cell nuclear antigen

Keap1:

Kelch-like ECH-associated protein 1

MTH:

Metallothionein

SOD:

Superoxide dismutase

GR:

Glutathione reductase

TUNEL:

Terminal deoxynucleotidyl transferase dUTP nick end labelling

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Funding

Financial assistance from the National Institute of Pharmaceutical Education and Research, S.A.S Nagar was provided to undertake the present study. Also, the Department of Science and Technology, Science and Engineering Research Board (DST‐SERB EMR/2015/001212/HS), Government of India provided financial assistance to carry out the present study.

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

    Aarzoo Charaya, Chittaranjan Sahu, Shivani Singla & Gopabandhu Jena

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  1. Aarzoo Charaya
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  2. Chittaranjan Sahu
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Aarzoo Charaya, Chittaranjan Sahu and Shivani Singla conceived, performed the experiments, analysed the data and Aarzoo Charaya and Shivani Singla wrote all the sections of the manuscript. G. B. Jena reviewed and proof-read the manuscript. Finally, all the authors approved the manuscript.

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Correspondence to Gopabandhu Jena.

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All institutional and national guidelines for the care and use of laboratory animals were followed. The animal studies were approved by the Animal Ethics Committee of the NIPER S.A.S Nagar (IAEC/16/52).

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12011_2022_3392_MOESM1_ESM.jpg

Supplementary file1 (JPG 2383 KB) Supplementary Fig. 1. Effect of ZDD and BPA on (A) line graph of feed intake at different time points; (B) line graph of water intake at different time points. All values are shown as mean ± SEM (n=5)

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Charaya, A., Sahu, C., Singla, S. et al. Zinc Deficiency Exacerbates Bisphenol A–Induced Hepatic and Renal Damage: Delineation of Molecular Mechanisms. Biol Trace Elem Res 201, 2879–2894 (2023). https://doi.org/10.1007/s12011-022-03392-3

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