Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy.

Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy.

Nature medicine (2013-03-12)

Feng Li, Jie Lu, Jie Cheng, Laiyou Wang, Tsutomu Matsubara, Iván L Csanaky, Curtis D Klaassen, Frank J Gonzalez, Xiaochao Ma

PMID23475203

ZUSAMMENFASSUNG

Co-therapy with rifampicin (RIF) and isoniazid (INH) used to treat tuberculosis in humans frequently causes liver injury. Here, using a pregnane X receptor (PXR)-humanized mouse model, we found that co-treatment with RIF and INH causes accumulation of the endogenous hepatotoxin protoporphyrin IX in the liver through PXR-mediated alteration of the heme biosynthesis pathway. These results provide insight into the mechanism of liver injury induced by co-treatment with these compounds and may lead to their safer use in the clinic.

MATERIALIEN

Produktnummer

Marke

Produktbeschreibung

P6774

Sigma-Aldrich

Phosphatase, alkalisch aus Rinderdarmschleimhaut, buffered aqueous solution, ≥2,000 DEA units/mg protein

P7640

Sigma-Aldrich

Phosphatase, alkalisch aus Rinderdarmschleimhaut, lyophilized powder, ≥10 DEA units/mg solid

P0114

Sigma-Aldrich

Phosphatase, alkalisch aus Rinderdarmschleimhaut, BioUltra, ≥5,700 DEA units/mg protein

I3377

Supelco

Isoniazid, analytical standard, ≥99% (TLC)

A8309

Sigma-Aldrich

Acethydrazid, 90%

P5521

Sigma-Aldrich

Phosphatase, alkalisch aus Rinderdarmschleimhaut, ≥2,000 DEA units/mg protein

P5931

Sigma-Aldrich

Phosphatase, alkalisch aus E. coli, lyophilized powder, 30-60 units/mg protein (in glycine buffer)

A2356

Sigma-Aldrich

Phosphatase, alkalisch aus Rinderdarmschleimhaut, ≥5,500 DEA units/mg protein

258385

Sigma-Aldrich

Protoporphyrin IX Dinatriumsalz, ≥90% (HPLC)

P4069

Sigma-Aldrich

Phosphatase, alkalisch aus E. coli, buffered aqueous glycerol solution, 20-50 units/mg protein (in glycine buffer)

P7923

Sigma-Aldrich

Phosphatase, alkalisch aus Rinderdarmschleimhaut, buffered aqueous glycerol solution, ≥4,000 DEA units/mg protein

P4252

Sigma-Aldrich

Phosphatase, alkalisch aus E. coli, ammonium sulfate suspension, 30-90 units/mg protein (modified Warburg-Christian, in glycine buffer)

P4439

Sigma-Aldrich

Phosphatase, alkalisch aus Schweineniere, lyophilized powder, ≥100 DEA units/mg protein

79390

Sigma-Aldrich

Phosphatase, alkalisch aus Kälberdarmschleimhaut, suitable for enzyme immunoassay, solution (clear, colorless), ~2500 U/mg protein (~10 mg/ml)

A2237

Sigma-Aldrich

Phosphatase, alkalische Garnelen, ≥900 DEA units/mL, buffered aqueous glycerol solution, recombinant, expressed in proprietary host

P8361

Sigma-Aldrich

Phosphatase, alkalisch Rind, recombinant, expressed in Pichia pastoris, ≥4000 units/mg protein