Protective effects of ibuprofen and its major metabolites against in vitro inactivation of catalase and fumarase: relevance to cataract.
Ibuprofen and its major metabolites were incubated with catalase and fumarase, in the presence of protein-modifying biomolecules, to explore the mode of action of ibuprofen in protection against cataract. Both 2 and 10 mM ibuprofen/metabolites protected catalase against fructose-, cyanate- and prednisolone-induced inactivation; the carboxy-metabolite gave the highest protection (31%). The 2 mM ibuprofen/metabolites protected fumarase against fructose- and cyanate-induced inactivation by up to 26%, but had no effect on prednisolone-induced inactivation. Ibuprofen/metabolites did not bind to catalase or fumarase. They penetrated into the lens in vitro. When in the lens, the metabolites may reduce the risk of cataract by protecting lenticular enzymes.
Shyadehi
Akbar Z
AZ
Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, OX2 6AW, UK. akbar.shyadehi@eye.ox.ac.uk
Harding
John J
JJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001711:Biotransformation; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002386:Cataract / Q000517:prevention & control; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005649:Fumarate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007052:Ibuprofen / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010539:Permeability
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D002374:Catalase; D005649:Fumarate Hydratase; D007052:Ibuprofen