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


METHODS
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.
Ministry of Health, Obstetrics and Gynecology Hospital, Igdır, Turkey. halis.suleyman@gmail.com
Suleyman
S
Salman
Serkan
S
Kumbasar
Yakup
Y
Kumtepe
Mehmet
M
Karaca
Bunyamin
B
Borekci
Kadir
K
Yildirim
Hamit Hakan
HH
Alp
Elif
E
Cadirci
Halis
H
Suleyman
D000311:Adrenal Glands / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D003345:Corticosterone / Q000097:blood*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D004837:Epinephrine / Q000097:blood*; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000188:drug therapy*; D008297:Male; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D004965:Estrogen Antagonists; D013629:Tamoxifen; D011239:Prednisolone; D051545:Cyclooxygenase 1; D003345:Corticosterone; D007213:Indomethacin; D004837:Epinephrine