Aristolochia manshuriensis Kom (AMK) is a member of the Aristolochiaceae family and is a well-known cause of aristolochic acid (AA) nephropathy. In this study, we investigated the potential of omeprazole (OM) to alleviate AMK-induced nephrotoxicity. We found that OM reduced mouse mortality caused by AMK and attenuated AMK-induced acute nephrotoxicity in rats. OM enhanced hepatic Cyp 1a1/2 and r...

Cytochrome P450 (CYP) enzymes participate in the metabolism of a variety of naturally occurring and foreign compounds by reactions requiring NADPH and O2. The diversity of reactions catalyzed and its extensive substrate specificity render CYP enzymes as one of the most versatile known catalysts. Individual members of the CYP superfamily are expressed in almost every cell type in the body. As co...

Background and Purpose Organic nitrates such as nitroglycerin (NTG) or pentaerythritol tetranitrate (PETN) have been used for over a century in the treatment of angina ischaemic heart disease. These compounds are prodrugs which release their nitrovasodilators upon enzymic bioactivation by aldehyde dehydrogenase (ALDH2) cytochromes P450 (CYP). Whereas ALDH2 is known to directly activate organic ...

Recent studies suggest that janus-activated kinases-signal transducer and activator of transcription signaling pathways contribute to increased voiding frequency and referred pain of cyclophosphamide (CYP)-induced cystitis in rats. Potential upstream chemical mediator(s) that may be activated by CYP-induced cystitis to stimulate JAK/STAT signaling are not known in detail. In these studies, memb...

Diterpene resin acids, together with monoterpenes and sesquiterpenes, are the most prominent defence chemicals in conifers. These compounds belong to the large group of structurally diverse terpenoids formed by enzymes known as terpenoid synthases. CYPs (cytochrome P450-dependent mono-oxygenases) can further increase the structural diversity of these terpenoids. While most terpenoids are charac...

Klinger MB, Vizzard MA. Role of p75 in female rat urinary bladder with cyclophosphamide-induced cystitis. Am J Physiol Renal Physiol 295: F1778–F1789, 2008. First published October 8, 2008; doi:10.1152/ajprenal.90501.2008.—Previous studies demonstrated changes in urinary bladder neurotrophin content and upregulation of neurotrophin receptors, TrkA and the p75 neurotrophin receptor (p75), in mic...

A cyclophilin (CyP) purified to homogeneity from the polycentric anaerobic rumen fungus Orpinomyces sp. strain PC-2 had a molecular mass of 20.5 kDa and a pI of 8.1. The protein catalyzed the isomerization of the prolyl peptide bond of N-succinyl-Ala-Ala-(cis,trans)-Pro-Phe p-nitroanilide with a kcat/Km value of 9.3 x 10(6) M-1.s-1 at 10 degrees C and pH 7.8. Cyclosporin A strongly inhibited th...

OBJECTIVES In this study, the objective was to determine the anti-inflammatory properties of CyP, a cyanobacterial lipopolysaccharide (LPS) antagonist, used in combination with antibiotic chemotherapy during infection of an in vitro meningitis model infected with Neisseria meningitidis (meningococcus). METHODS Monocultures of human meningioma cells and meningioma-primary human macrophage co-c...

The Cytochrome P450 super family (CYP) is responsible for a wide range of functions in metazoans, having roles in both exogenous and endogenous substrate metabolism. Annelids are known to metabolize polycyclic aromatic hydrocarbons (PAHs) and produce estrogen. CYPs are postulated to be key enzymes in these processes in annelids. In this study, the CYP complement (CYPome) of the annelid Capitell...

TRPV4 antagonist RN-1734 and by inhibition of endothelial Ca-activated K channels. In native and TRPV4-overexpressing human coronary artery ECs (HCAECs), AA increased intracellular Ca concentration ([Ca]i), which was mediated by TRPV4-dependent Ca entry. The AA-induced [Ca]i increase was inhibited by cytochrome P450 (CYP) inhibitors. Surprisingly, the CYP metabolites of AA, epoxyeicosatrienoic ...