Biomaterial Database

Alteration of acetaminophen metabolism by sulfate and steroids in primary monolayer hepatocyte cultures of rats and mice. 1999

K W Seo, and M H Oh, and S Y Choung, and S J Kim, and H J Kim

Department of Toxicology, Korea Food and Drug Administration, Eunpyunggu, Seoul.

Sulfotransferase (ST) is considered to be generally not induced by xenobiotics. However, it has been reported that steroids such as dexamethasone (DEX) and pregnenolone-16a-carbonitrile (PCN) are effective ST inducers in rats, and sulfation of xenobiotics is quite different in rats and mice. The present study is primarily aimed at determining the effect of sulfate and steroids on the metabolism of acetaminophen (AA) in vitro using monolayer cultured hepatocytes of Sprague-Dawley rats and ICR mice. Hepatocytes of rats and mice were incubated with inorganic sulfate (0.25, 0.5, 1.0, 2.0, 4.0 mM) and AA in SO4-depleted media. AA sulfation rates increased as the sulfate concentration was raised to 1.0 mM in rats, whereas the addition of inorganic sulfate to the media had a lesser effect in mice hepatocytes. After pretreatment with DEX (0.1, 1.0, 10, 100 microM) and PCN (0.1, 1.0, 10 microM) for 3 d, hepatocytes were incubated with AA in media containing 4.0 mM SO4-. Pretreatment of the hepatocytes with DEX caused an increase in the glucuronidation and sulfation of AA by 2-3 folds in rats, but to a lesser extent in mice. PCN significantly enhanced the formation of AA-glucuronide and AA-sulfate in mice, but had a minimal effect on rat hepatocytes. In summary, sulfate and DEX markedly enhanced the formation of AA-sulfate in rats hepatocytes, and DEX and PCN increased the sulfation of AA in mice hepatocytes. These results partially support the claim that DEX and PCN are effective ST and uridine diphosphate-glucuronyltransferase inducers in vivo.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008297	Male		Males
D008813	Mice, Inbred ICR	An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER.	Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
D011285	Pregnenolone Carbonitrile	A catatoxic steroid and microsomal enzyme inducer having significant effects on the induction of cytochrome P450. It has also demonstrated the potential for protective capability against acetaminophen-induced liver damage.	PCN,Pregnenolone 16 alpha-Carbonitrile,Pregnenolone Carbonitrile, (3 beta)-Isomer,Pregnenolone Carbonitrile, (3 beta,16 beta)-Isomer,16 alpha-Carbonitrile, Pregnenolone,Carbonitrile, Pregnenolone,Pregnenolone 16 alpha Carbonitrile
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D005938	Glucocorticoids	A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.	Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D000082	Acetaminophen	Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.	Acetamidophenol,Hydroxyacetanilide,Paracetamol,APAP,Acamol,Acephen,Acetaco,Acetominophen,Algotropyl,Anacin-3,Datril,N-(4-Hydroxyphenyl)acetanilide,N-Acetyl-p-aminophenol,Panadol,Tylenol,p-Acetamidophenol,p-Hydroxyacetanilide,Anacin 3,Anacin3
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013045	Species Specificity	The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.	Species Specificities,Specificities, Species,Specificity, Species