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

Aarzoo Charaya, Chittaranjan Sahu, Shivani Singla, Gopabandhu Jena
Author Information
  1. Aarzoo Charaya: 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.
  2. Chittaranjan Sahu: 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.
  3. Shivani Singla: 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.
  4. Gopabandhu Jena: 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. gbjena@niper.ac.in.

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.

Keywords

References

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Grants

  1. EMR/2015/001212/HS/Science and Engineering Research Board
  2. NPLC-GBJ-2018-19/NIPER, S.A.S Nagar

MeSH Term

Rats
Male
Animals
Rats, Sprague-Dawley
Liver
Zinc
Malnutrition
Kidney
Oxidative Stress

Chemicals

bisphenol A
Zinc

Word Cloud

Created with Highcharts 10.0.0BPAZnZn-deficientsystemsdietZDD100 mg/kg/dZincsystemdeficiencyhepaticrenalBisphenolcanoxidativestressdamageliverkidneyratsynergisticinducedproteinnuclearfactorplaysimportantrolemaintenanceredoxstatusbiologicalfoundassociatednegativeeffectsfunctioningmanyorganincludingalterhomeostasisperturbphysiologicalprovokingleaddifferentorgansreproductiveimmuneneuroendocrinepresentstudyaimsinvestigatetoxicitydeficientconditioncorrelateactionsfeedingadministeredorallyMaleSprague-Dawleyratsdividedfourgroups:NPD + VehiclenormalfeedwaterNPD + BPAZDD + VehiclefedZDD + BPAdiet + BPA8 weeksBiochemicalhistopathologicalTUNELassayexpressionprofilesdetermineddeciphertoxicantExpressionprofileerythroid2-related2proliferatingcellantigenkelch-likeECH-associated1superoxidedismutase-1metallothioneinapoptosisincidenceshowedexacerbationeffectDeficiencyExacerbatesA-InducedHepaticRenalDamage:DelineationMolecularMechanismsKidneyLiverOxidative

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