In vitro glucuronidation of bisphenol A in liver and intestinal microsomes: interspecies differences in humans and laboratory animals. (4th July 2022)

• Record Type: Journal Article
• Authors: Hanioka, Nobumitsu; Isobe, Takashi; Tanaka-Kagawa, Toshiko; Jinno, Hideto; Ohkawara, Susumu
• Is Part Of: Drug and chemical toxicology. Volume 45:Number 4(2022)
• Page Start: 1565
• Page End: 1569
• Publication Date: 2022-07-04
• Subjects: Bisphenol A (BPA) -- glucuronidation -- UDP-glucuronosyltransferase (UGT) -- liver microsomes -- intestinal microsomes; Toxicology -- Periodicals; Drugs -- Toxicology -- Periodicals; Toxicology, Experimental -- Periodicals; 615.9005
• DOI: 10.1080/01480545.2020.1847133
• Languages: English
• ISSNs: 0148-0545

Abstract

Abstract: Bisphenol A (BPA) is an endocrine-disrupting chemical, and is predominantly metabolized into glucuronide in mammals. The present study was conducted in order to examine the hepatic and intestinal glucuronidation of BPA in humans and laboratory animals such as monkeys, dogs, rats, and mice in an in vitro system using microsomal fractions. K m, V max, and CL int values in human liver microsomes were 7.54 µM, 17.7 nmol/min/mg protein, and 2.36 mL/min/mg protein, respectively. CL int values in liver microsomes of monkey, dogs, rats, and mice were 1.5-, 2.4-, 1.7- and 8.2-fold that of humans, respectively. In intestinal microsomes, K m, V max, and CL int values in humans were 39.3 µM, 0.65 nmol/min/mg protein, and 0.02 mL/min/mg protein, respectively. The relative levels of CL int in monkey, dogs, rats, and mice to that of humans were 7.0-, 12-, 34-, and 29-fold, respectively. Although CL int values were higher in liver microsomes than in intestinal microsomes in all species, and marked species difference in the ratio of liver to intestinal microsomes was observed as follows: humans, 118; monkeys, 25; dogs, 23; rats, 5.9; mice, 33. These results suggest that the functional roles of UDP-glucuronosyltransferase (UGT) enzymes expressed in the liver and intestines in the metabolism of BPA extensively differ among humans, monkeys, dogs, rats, and mice.