Suppressed farnesoid X receptor by iron overload in mice and humans potentiates iron-induced hepatotoxicity.

Background And Aims: Iron overload (IO) is a frequent finding in the general population. As the major iron storage site, the liver is subject to iron toxicity. Farnesoid X receptor (FXR) regulates bile acid metabolism and is implicated in various liver diseases.

Comparative toxicity analysis of corannulene and benzo[a]pyrene in mice.

Increasing production of corannulene (COR), a non-planar polycyclic aromatic hydrocarbon (PAH) with promising applications in many fields, has raised a concern about its potential toxic effects. However, no study has been undertaken to evaluate its metabolism and toxicity in mammals. In this study, the acute toxicities of COR in mice were compared with benzo[apyrene (BaP), a typical planar PAH with almost the same molecular weight.

Glucocorticoids Increase Renal Excretion of Urate in Mice by Downregulating Urate Transporter 1.

Both nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids have been widely used for the treatment of gout, a disease promoted by an excess body burden of uric acid (UA); however, their effects on the homeostasis of UA remain poorly understood. The present study showed that 1-week treatments with three NSAIDs (ibuprofen, diclofenac, and indomethacin) had little effect on UA homeostasis in mice, whereas 1-week low doses (1 and 5 mg/kg) of dexamethasone (DEX) significantly decreased serum UA by about 15%. Additionally, low doses of DEX also resulted in increases in hepatic UA concentration and urinary UA excretion, which were associated with an induction of xanthine oxidoreductase (XOR) in the liver and a downregulation of urate transporter 1 (URAT1) in the kidney, respectively.