The effect of indomethacin administration on the splenic changes induced by estradiol supplementation in ovariectomized New Zealand white rabbits.

ABSTRACT

In an effort to elucidate the mechanism by which indomethacin (IN) lessens the stimulatory effect of estradiol (E2) on rabbit splenic red pulp macrophages (RPMs), 39 female New Zealand White rabbits were divided into 10 groups ovariectomized (OVX) and OVX/IN at 0.1 and 5.0 mg/kg body weight (bw)/day; sham OVX (SOVX) and SOVX/IN at 0.1 and 5.0 mg/kg bw/day; OVX/25 mg E2 and OVX/25 mg E2/IN at 0.1 and 5.0 mg/kg bw/day; and intact control. Changes in RPM population in response to treatment were measured using a 0-4 histologic grade. Estradiol treatment resulted in increased RPM grade when compared to the OVX groups. Indomethacin addition lowered mean RPM grade in the SOVX/IN 5.0 group when compared to its E2 control group. Indomethacin administration had no significant effect on levels of prostaglandin E2 in spleen, urine, or blood. Hematocrits were reduced in both OVX and OVX/E2 groups; this decrease was exacerbated by the high IN dose. In summary, the results from this study suggest that the effect of IN on E2-induced RPM activation may be mediated through a nonprostaglandin pathway. The observed hematocrit changes are possibly the result of direct action of IN and E2 on erythrocytes, resulting in their accelerated clearance from the circulation by splenic RPM.