Pathophysiological mechanism of ibuprofen-incurred renal failure and enzymology and metabolic stereoisomeric inversion of ibuprofen
Ibuprofen-induced interstitial nephritis was proposed to be a manifestation of a disordered cell-mediated immunity. To test the hypothesis that ibuprofen-induced interstitial nephritis is attributed to a disordered cellular immunity, the highly specific anti-ibuprofen antiserum was developed by injecting rats with the ibuprofen conjugate of keyhole limpet hemocyanin (KLH). Ibuprofen-associated interstitial nephritis was studied by using a rabbit model. Rabbits of uranyl nitrate treatment induced temporary renal failure, and the effect of chronic ibuprofen regimen was studied.^ Pathological examinations of the kidney specimens showed marked lymphocytic aggregation in the perivascular area. The infiltrated lymphocytes were confirmed to be T-lymphocytes by using anti-CD43 antibody. The aggregated T-lymphocytes support that cellular immunity may play a role in ibuprofen-induced interstitial nephritis. However, no ibuprofen conjugates could be detected by the anti-ibuprofen antibody. The lymphocyte stimulation test (LST), the most effective method to study allergen, showed that ibuprofen stimulated the differentiation of lymphocytes. These studies suggest that disordered cell immunity may play a role in ibuprofen-associated interstitial nephritis.^ The 2-arylpropionyl-CoA epimerase (2-APE) has been purified from rat liver cytosol and mitochondria for the immunological study. The homogeneity of both enzyme preparations was shown by SDS-PAGE with molecular mass of 42 kDa. The 2-APEs from rat cytosol and mitochondria are immunological related. They may display common epitopes in the native conformation. The tissue distribution using anti-2-APE antiserum showed that 42 kDa epimerase could only be detected in the crude exacts from liver and kidney. In addition, the epimerase activity in both rat liver and kidney could be inhibited by the antiserum.^ The 2-APE has been partially purified from the cytosol of human liver. The enzyme is an extremely minute component in human liver with an apparent molecular mass of 55 kDa. It has no apparent requirement for exogenous cofactors, but required dithiothreitol to maintain the stability. The human 2-APE activity could not be neutralized by the antiserum against rat liver 2-APE, which suggests that the 2-APEs from human and rat livers are not immunologically related. ^
Health Sciences, Pharmacology|Chemistry, Biochemistry|Health Sciences, Immunology
"Pathophysiological mechanism of ibuprofen-incurred renal failure and enzymology and metabolic stereoisomeric inversion of ibuprofen"
Dissertations and Master's Theses (Campus Access).