Effects of Diclofenac, Piroxicam and α-Tocopherol on Monoamine-lymphopoietic Interfacing in Mice

Abstract

The non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac (CAS 15307-79-6) and piroxicam (CAS 36322-90-4) were shown in previous works to induce bone marrow lymphopoiesis. The present work aimed at evaluating the extent to which lymphopoietic effects of the above mentioned drugs as well as their interactions with alpha-tocopherol (CAS 10191-41-0) may be reflected in changes in the tissue levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT). The study was performed in male adult mice. The doses were given once daily for 7 days. The evaluations were performed in 2 phases. First, dose-response relationships of each of diclofenac, piroxicam and alpha-tocopherol were evaluated using bone marrow lymphocytes counts and monoamines levels in plasma, brain and spleen. Then, interactions of alpha-tocopherol (10 mg/kg) with diclofenac (20 mg/kg) and piroxicam (3 mg/kg), respectively, were evaluated. The interaction evaluations included effects on bone marrow lymphocytes count, monoamines levels in plasma, brain, spleen and thymus, as well as spleen weight. The obtained findings revealed that diclofenac, piroxicam and alpha-tocopherol decreased NE and DA levels in plasma, brain and spleen. There was some correlation between the decrease in plasma NE and the bone marrow lymphopoiesis. Pre-administration of alpha-tocopherol failed to maintain monoamines levels at the range of normal values in plasma, brain and spleen of NSAIDs-treated mice except splenic DA levels. In addition, the decrease in NE level induced by administration of piroxicam or diclofenac, either alone or together with a-tocopherol, corresponded to the increase in bone marrow lymphopoiesis. The present work suggests that the diclofenac- and piroxicam-induced bone marrow lymphopolesis as well as their respective interactions with alpha-tocopherol are associated with parallel changes in monoamines levels, especially those of NE and 5-HT.