Effects of developmental exposures to Bisphenol-A and Bisphenol-S on hepatocellular function in male Long-Evans rats

Keyi Liu; Surekha Kadannagari; Jack Deruiter; Suhrud Pathak; Kodye L Abbott; Julia M Salamat; Satyanarayana R Pondugula; Benson T Akingbemi; Muralikrishnan Dhanasekaran

doi:10.1016/j.lfs.2023.121752

Effects of developmental exposures to Bisphenol-A and Bisphenol-S on hepatocellular function in male Long-Evans rats

Life Sci. 2023 Aug 1:326:121752. doi: 10.1016/j.lfs.2023.121752. Epub 2023 May 10.

Authors

Keyi Liu¹, Surekha Kadannagari¹, Jack Deruiter¹, Suhrud Pathak¹, Kodye L Abbott², Julia M Salamat², Satyanarayana R Pondugula², Benson T Akingbemi², Muralikrishnan Dhanasekaran³

Affiliations

¹ Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, AL, USA.
² Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
³ Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, AL, USA. Electronic address: dhanamu@auburn.edu.

PMID: 37172818
DOI: 10.1016/j.lfs.2023.121752

Abstract

Bisphenol-S (BPS) is a current substitute for Bisphenol-A (BPA) in various commercial products (paper, plastics, protective can-coatings, etc.) used by all age groups globally. The current literature indicates that a drastic surge in pro-oxidants, pro-apoptotic, and pro-inflammatory biomarkers in combination with diminished mitochondrial activity can potentially decrease hepatic function leading to morbidity and mortality. Consequently, there are increasing public health concerns that substantial Bisphenol-mediated effects may impact hepatocellular functions, particularly in newborns exposed to BPA and BPS postnatally. However, the acute postnatal impact of BPA and BPS and the molecular mechanisms affecting hepatocellular functions are unknown. Therefore, the current study investigated the acute postnatal effect of BPA and BPS on the biomarkers of hepatocellular functions, including oxidative stress, inflammation, apoptosis, and mitochondrial activity in male Long-Evans rats. BPA and BPS (5 and 20 microgram/Liter (μg/L) of drinking water) were administered to 21-day-old male rats for 14 days. BPS had no significant effect on apoptosis, inflammation, and mitochondrial function but significantly reduced the reactive oxygen species (51-60 %, **p < 0.01) and nitrite content (36 %, *p < 0.05), exhibiting hepatoprotective effects. As expected, based on the current scientific literature, BPA induced significant hepatoxicity, as seen by significant glutathione depletion (50 %, *p < 0.05). The in-silico analysis indicated that BPS is effectively absorbed in the gastrointestinal tract without crossing the blood-brain barrier (whereas BPA crosses the blood-brain barrier) and is not a substrate of p-Glycoprotein and Cytochrome P450 enzymes. Thus, the current in-silico and in vivo findings revealed that acute postnatal exposure to BPS had no significant hepatotoxicity.

Keywords: Acute toxicity; Bisphenol-A & Bisphenol-S; Hepatotoxicity; Oxidative stress; Postnatal; Rodents (Long Evans).

MeSH terms

Animals
Benzhydryl Compounds / toxicity
Carcinoma, Hepatocellular*
Inflammation
Liver Neoplasms*
Male
Rats
Rats, Long-Evans
Reactive Oxygen Species

Substances

Reactive Oxygen Species
bis(4-hydroxyphenyl)sulfone
bisphenol A
Benzhydryl Compounds