Prior induction of an endoplasmic reticulum stress response results in protection against reactive cytotoxins in the LLC-PK1 cell line. The purpose of this investigation was to determine therefore if the endoplasmic reticulum was disrupted by iodoacetamide, tert-butylhydroperoxide or sulfamethoxazol...

Interferon and interferon inducers are well known to depress hepatic cytochrome P-450 (P-450). Previous reports have suggested that all constitutive members of the P-450 family of proteins are affected in this manner, whereas inducible P-450s--including cytochrome P-4503A1 (CYP3A1)--are resistant to...

The expression of constitutive and inducible cytochrome P450s has been shown to be downregulated by interferon through an unknown pretranslational mechanism that depresses the mRNA encoding P450 apoproteins. To establish an association between gene transcription and P450 apoprotein downregulation by...

The clearance of sulphamethoxazole (SMX), a compound metabolised primarily by the N-acetyltransferase NAT1, is increased in cystic fibrosis (CF) patients. We assessed the activity and kinetic properties of NAT1 in lysates of peripheral blood mononuclear leukocytes (MNL) from CF (n = 17) and control ...

The oxidation of sulfamethoxazole to its hydroxylamine metabolite was investigated in vitro with human liver microsomes and in vivo by detection in the urine. Sulfamethoxazole was oxidized to the hydroxylamine in an NADPH-dependent process by liver microsomes prepared from two human livers. Three he...

The hydroxylamine and nitroso metabolites formed by N4-oxidation of sulfonamides are thought to be involved in the pathogenesis of idiosyncratic reactions to this class of drugs. Idiosyncratic reactions to sulfonamides are characterized by multisystemic toxicity, including hepatitis, nephritis, derm...

Sulphonamide hypersensitivity reactions are believed to be mediated through reactive intermediates derived from oxidation of the para-amino group to form sulphonamide hydroxylamines. Sulphamethoxazole hydroxylamine (SMX-HA) can be acetylated by N-acetyltransferase (NAT) enzymes to form an acetoxy me...

Sulfonamides are oxidized to protein reactive cytotoxic metabolites by murine hepatic microsomes. Mononuclear leukocytes from patients with idiosyncratic reactions to sulfonamides were more susceptible to toxicity from these metabolites than were leukocytes from a control population, suggesting that...