Pistacia integerrima alleviated Bisphenol A induced toxicity through Ubc13/p53 signalling

Mol Biol Rep. 2020 Sep;47(9):6545-6559. doi: 10.1007/s11033-020-05706-x. Epub 2020 Aug 8.

Abstract

Exposure to environmental toxicants such as Bisphenol A (BPA) has raised serious health issues globally particularly in developing countries. It is ubiquitously used in the manufacturing of canned food and feeding bottles. BPA generated reactive oxygen species can lead to several diseases including cardiotoxicity. However, the endpoints stimulated in BPA cardiotoxicity yet need to be investigated. The current study was aimed to investigate the underlying molecular pathways which may contribute in revealing the protective effects of Pistacia integerrima against BPA induced oxidative stress. The dose of 100 µg/kg BW of BPA, 200 mg/kg BW P. integerrima, and 4 mg/kg BW melatonin was administered to Sprague Dawley rats. Present results of western blotting and qRT-PCR showed the increased expression of p53, PUMA and Drp1, while downregulation of Ubc13 in heart tissues of BPA treated group whereas the levels were reversed upon treatment with P. integerrima. The role of BPA in heart tissue apoptosis was further confirmed by the increased level of P-p53, cytochrome C and disrupted cellular architecture whereas the P. integerrima has shown its ameliorative potential by mitigating the adverse effects of BPA. Moreover, the oxidant, antioxidant, lipid, and liver markers profile has also revealed the therapeutic potential of P. integerrima by maintaining the levels in the normal range. However, melatonin has also manifested the normalized expression of apoptotic markers, biochemical markers, and tissue architecture. Conclusively, the data suggest that P. integerrima may be a potential candidate for the treatment of BPA induced toxicity by neutralizing the oxidative stress through Ubc13/p53 pathway.

Keywords: Antioxidants; BPA; Environmental toxicant; Pistacia integerrima gall; Toxicity.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / toxicity*
  • Blood Glucose / drug effects
  • Cytochromes c / metabolism
  • Dynamins / genetics
  • Dynamins / metabolism
  • Female
  • Hypodermoclysis
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / pathology
  • Lipid Metabolism / drug effects
  • Liver / cytology
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Melatonin / administration & dosage
  • Melatonin / pharmacology
  • Oxidative Stress / drug effects*
  • Phenols / administration & dosage
  • Phenols / toxicity*
  • Pistacia / chemistry*
  • Plant Extracts / administration & dosage
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Tumors
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitin-Conjugating Enzymes / genetics
  • Ubiquitin-Conjugating Enzymes / metabolism*
  • Up-Regulation

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Bbc3 protein, rat
  • Benzhydryl Compounds
  • Blood Glucose
  • Phenols
  • Plant Extracts
  • Reactive Oxygen Species
  • Tp53 protein, rat
  • Tumor Suppressor Protein p53
  • Cytochromes c
  • Ube2n protein, rat
  • Ubiquitin-Conjugating Enzymes
  • Dnm1l protein, rat
  • Dynamins
  • Melatonin
  • bisphenol A