Role of adrenal gland hormones in the anti-inflammatory effect mechanism of tamoxifen, a partial antagonist for oestrogen receptors, and relation with COX levels

Abstract

Objective. There is limited study about anti-inflammatory effect mechanism of tamoxifen. We aimed to investigate the anti-inflammatory activity of tamoxifen to see whether adrenal gland hormones have roles in the anti-inflammatory effect mechanism of tamoxifen and to evaluate the relationship between anti-inflammatory activity and cyclooxygenase (COX) level.

Study Design. Effects of tamoxifen, indomethacin and prednisolon on carrageenan-induced inflammatory paw oedema were investigated in intact and adrenalectomised rats. Also blood adrenalin and corticosterone levels and paw tissue COX levels determined biochemically.

Results. Tamoxifen (5, 10 and 20 mg/kg), indomethacin (5, 10 and 20 mg/kg) and prednisolon (5 mg/kg) produced anti-inflammatory effects in intact rats, however, they could not in adrenalectomized rats. 20 mg/kg tamoxifen produced low anti-inflammatory effect. Tamoxifen and indomethacin decreased COX-2 levels in intact rats, but not in adrenalectomised rats. Tamoxifen produced anti-inflammatory effects by decreasing adrenalin levels, as indomethacin does. 20 mg/kg tamoxifen decreased corticosterone levels.

Conclusions. Tamoxifen was seen to suppress carrageenan-induced inflammation significantly. The dose of tamoxifen that decreases adrenalin levels maximally and decreases corticosterone levels minimally was found to produce the most potent anti-inflammatory effect. The reason why indomethacin is more potent in high doses may be that it decreases adrenalin levels strongly at these doses, without decreasing corticosterone levels.

Keywords:

• Tamoxifen
• inflammation
• adrenalin
• corticosterone
• cyclooxygenase
• rat

Acknowledgements

We thank Assoc. Prof. Zekai Halici and Ms. Beyzagul Polat for their contributions to this work.