Resveratrol Butyrate Esters Inhibit BPA-Induced Liver Damage in Male Offspring Rats by Modulating Antioxidant Capacity and Gut Microbiota

Int J Mol Sci. 2021 May 17;22(10):5273. doi: 10.3390/ijms22105273.


Resveratrol can affect the physiology or biochemistry of offspring in the maternal-fetal animal model. However, it exhibits low bioavailability in humans and animals. Fifteen-week SD pregnant female rats were orally administered bisphenol A (BPA) and/or resveratrol butyrate ester (RBE), and the male offspring rats (n = 4-8 per group) were evaluated. The results show that RBE treatment (BPA + R30) compared with the BPA group can reduce the damage caused by BPA (p < 0.05). RBE enhanced the expression of selected genes and induced extramedullary hematopoiesis and mononuclear cell infiltration. RBE increased the abundance of S24-7 and Adlercreutzia in the intestines of the male offspring rats, as well as the concentrations of short-chain fatty acids (SCFAs) in the feces. RBE also increased the antioxidant capacity of the liver by inducing Nrf2, promoting the expression of HO-1, SOD, and CAT. It also increased the concentration of intestinal SCFAs, enhancing the barrier formed by intestinal cells, thereby preventing BPA-induced metabolic disruption in the male offspring rats, and reduced liver inflammation. This study identified a potential mechanism underlying the protective effects of RBE against the liver damage caused by BPA exposure during the peri-pregnancy period, and the influence of the gut microbiota on the gut-liver axis in the offspring.

Keywords: bisphenol A (BPA); gut microbiota; maternal/fetal animal model; offspring; resveratrol butyrate esters (RBE); short-chain fatty acids (SCFAs).

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Benzhydryl Compounds / adverse effects*
  • Benzhydryl Compounds / pharmacology
  • Butyrates / metabolism
  • Esters / metabolism
  • Fatty Acids, Volatile / metabolism
  • Female
  • Gastrointestinal Microbiome
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / metabolism
  • Liver Diseases / prevention & control*
  • Male
  • Phenols / adverse effects*
  • Phenols / pharmacology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol / analogs & derivatives
  • Resveratrol / pharmacology*


  • Antioxidants
  • Benzhydryl Compounds
  • Butyrates
  • Esters
  • Fatty Acids, Volatile
  • Phenols
  • bisphenol A
  • Resveratrol