Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels

Dairam, A; Antunes, Edith M; Saravanan, K S; Daya, Santylal

Title: Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels
Creator: Dairam, A, Antunes, Edith M, Saravanan, K S, Daya, Santylal
Date: 2006
Type: Article
Identifier: vital:6358
Identifier: http://hdl.handle.net/10962/d1006050
Identifier: http://dx.doi.org/10.1016/j.lfs.2006.07.028
Description: Hepatic tryptophan 2,3-dioxygenase (TDO) is one of the rate-limiting enzymes in tryptophan catabolism and plays an important role in regulating the physiological flux of tryptophan into relevant metabolic pathways. In this study, we determined the effect of the non-steroidal anti-inflammatory agents, tolmetin and sulindac, on rat liver TDO activity and the subsequent changes in the hippocampal and striatal neurotransmitter levels. The amount of melatonin produced by the pineal gland was also measured using high performance liquid chromatography (HPLC). Treatment of rats with tolmetin or sulindac (5 mg/kg/bd for 5 days) significantly inhibited liver TDO activity. The results show that whilst tolmetin and sulindac increase serotonin levels in the hippocampus, these agents also significantly reduce dopamine levels in the striatum. Tolmetin, but not sulindac, increased the amount of melatonin produced by the pineal gland. The results of this study suggest that whilst tolmetin and sulindac may be beneficial for patients suffering from depression, these agents also have the potential to induce adverse effects in patients suffering with neurological disorders such as Parkinson's disease.
Format: 10 pages, pdf
Language: English
Relation: Dairam, A. and Antunes, Edith Martins and Saravanan, K.S. and Daya, S. (2006) Non-steroidal anti-inflammatory agents, tolmetin and sulindac, inhibit liver tryptophan 2,3-dioxygenase activity and alter brain neurotransmitter levels. Life Sciences, 79 (24). pp. 2269-2274. Available: http://dx.doi.org/10.1016/j.lfs.2006.07.028

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Daya, Santylal (Prof)

Antunes, Edith Martins (Dr)

RU Department of Pharmacy

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