ABSTRACT
Inflammation is a cellular defensive mechanism associated to oxidative stress. The administration of nitrofurantoin, nifurtimox and acetaminophen generates oxidative stress by their biotransformation through CYP450 system. The main adverse effect described for the first two drugs is gastrointestinal inflammation and that of the last, hepatitis. Therefore, standardised dry extracts from Rosmarinus officinalis, Buddleja globosa Hope, Cynara scolymus L., Echinacea purpurea and Hedera helix were tested to evaluate their capacity to decrease drug-induced oxidative stress. For that, rat liver microsomes were incubated with drugs in the presence of NADPH (specific CYP450 system cofactor) to test oxidative damage on microsomal lipids, thiols, and GST activity. All drugs tested induced oxidation of microsomal lipids and thiols, and inhibition of GST activity. Herbal extracts prevented these phenomena in different extension. These results show that antioxidant phytodrugs previously evaluated could alleviate drugs adverse effects associated to oxidative stress.
Inflamación es un mecanismo de defensa el cual está asociado a estrés oxidativo. La administración de nitrofurantoína, nifurtimox y paracetamol genera estrés oxidativo al metabolizarse a través del sistema CYP450. El principal efecto adverso de los dos primeros fármacos es inflamación gastrointestinal y del tercero, hepatitis. Por lo tanto, utilizamos diversos extractos herbales para disminuir el estrés oxidativo inducido por estos fármacos. Para esto se incubaron microsomas hepáticos de rata con dichos fármacos en presencia de NADPH (cofactor específico del sistema CYP450) y se evaluó el daño oxidativo generado sobre los lípidos, los tioles y la actividad GST microsómica. Todos los fármacos indujeron oxidación de los lípidos y los tioles microsómicos e inhibieron la actividad GST. Los extractos herbales previnieron estos fenómenos oxidativos en diferente extensión. Estos resultados indican que fitofármacos antioxidantes previamente evaluados, podrían aliviar los efectos adversos asociados a estrés oxidativo de los fármacos.
Subject(s)
Animals , Male , Antioxidants/pharmacology , Microsomes, Liver/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Acetaminophen/adverse effects , Glutathione Transferase/metabolism , Lipid Peroxidation , Microsomes, Liver/enzymology , NADP/analysis , Nifurtimox/adverse effects , Nitrofurantoin/adverse effects , Plant Extracts/chemistry , Polyphenols/analysis , Rats, Sprague-Dawley , Sulfhydryl CompoundsABSTRACT
OBJECTIVE: To evaluate the antioxidant effects of synovial fluid (SF) pooled from metacarpophalangeal joints of healthy horses and horses with various pathological conditions, and to compare then with the antioxidant effects of hyaluronic acid (HA) and chondroitin sulfate (CS). SAMPLE POPULATION: SF from 1 metacarpophalangeal joint was obtained from 42 horses immediately after humane slaughter. Samples were classified into 3 groups on the basis of origin: healthy joints or joints with chronically damaged cartilage or vascularly congested synovial membranes as detected via macroscopic evaluation. PROCEDURES: Antioxidant effects were evaluated by use if rat liver microsomal fractions treated with Fe(3+)-ascorbate as a free radical generator system leading to oxidative stress. Amounts of thiobarbituric-reactive substances and glutathione transferase (GSH-T) conjugation activity were measured. RESULTS: SF from healthy and chronically damaged joints inhibited microsomal lipid peroxidation, whereas SF from joints with congested synovial membranes had only a slight effect. Hyaluronic acid and CS did not inhibit microsomal lipid peroxidation. Moreover, GSH-T activity was detected in all SF samples as well as HA and CS protected rat microsomal GSH-T activity against oxidative damage. Only SF samples from joints with congested synovial membranes protected microsomal thiols against oxidation, an effect also evident with HA and CS. CONCLUSIONS AND CLINICAL RELEVANCE: The antioxidant mechanisms associated with the response to metacarpophalangeal joint damage in horses appeared to act on different targets, depending on whether the damage was acute or chronic.
