Histological changes caused by meclofenamic acid in androgen independent prostate cancer tumors: evaluation in a mouse model

ABSTRACT Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity. Further studies are needed to evaluate the molecular changes that cause the beneficial and therapeutic effects of meclofenamic acid in androgen-independent prostate cancer.

Role of nitric oxide and prostaglandin in the maintenance of cortical and renal medullary blood flow

This study was undertaken in anesthetized dogs to evaluate the relative participation of prostaglandins (PGs) and nitric oxide (NO) in the maintenance of total renal blood flow (TRBF), and renal medullary blood flow (RMBF). It was hypothesized that the inhibition of NO should impair cortical and medullary circulation because of the synthesis of this compound in the endothelial cells of these two territories. In contrast, under normal conditions of perfusion pressure PG synthesis is confined to the renal medulla. Hence PG inhibition should predominantly impair the medullary circulation. The initial administration of 25 µM kg-1 min-1 NG-nitro-L-arginine methyl ester produced a significant 26 percent decrease in TRBF and a concomitant 34 percent fall in RMBF, while the subsequent inhibition of PGs with 5 mg/kg meclofenamate further reduced TRBF by 33 percent and RMBF by 89 percent. In contrast, the initial administration of meclofenamate failed to change TRBF, while decreasing RMBF by 49 percent. The subsequent blockade of NO decreased TRBF by 35 percent without further altering RMBF. These results indicate that initial PG synthesis inhibition predominantly alters the medullary circulation, whereas NO inhibition decreases both cortical and medullary flow. This latter change induced by NO renders cortical and RMBF susceptible to a further decrease by PG inhibition. However, the decrease in medullary circulation produced by NO inhibition is not further enhanced by subsequent PG inhibition.

Efecto del ácido meclofenámico sobre la pérdida de sangre menstual en mujeres hipermenorreicas usuarias de dispositivo intrauterino / Effect of meclofenamic acid on menstrual bleeding of hypermenorrheic women users of intrauterine devices

Con el objeto de evaluar el efecto del ácido meclofenámico sobre la pérdida de sangre menstrual en mujeres usuarias de dispositivo intrauterino, afectas a hipermenorrea, se administró este producto en dosis de 100 mg cada 8 horas por 3 días durante 2 ciclos menstruales consecutivos a una población seleccionada de pacientes de nuestro consultorio de planificación familiar, en las que la medición de la pérdida de sangre menstrual promedio durante dos ciclos consecutivos con la administración de un placebo fue de 60 o más ml por período. De un total de 40 pacientes reclutadas, 20 iniciaron la ingesta del fármaco en el período premenstrual inmediato y 20 iniciaron la ingesta del fármaco en el primer día menstrual. En el grupo menstrual, el 80% de las pacientes presentó una reducción de la pérdida de sangre menstrual al comparar los 2 ciclos placebo versus ciclos de tratamiento (reducción promedio de 25,2 ml por ciclo). En el grupo premenstrual el 70% de las pacientes presentó respuesta reductora de la pérdida de sangre menstrual, con reducción promedio de 30,3 ml por ciclo (25,1%). La similitud de respuesta, sumada a otras ventajas, aconseja el inicio de la ingesta del ácido meclofenámico en el primer día menstrual. La magnitud de la respuesta reductora de la pérdida de sangre menstrual representa un importante efecto benéfico sobre el balance del metabolismo del fierro en mujeres usuarias de dispositivo intrauterino. La no respuesta del total de pacientes al ácido meclofenámico permite entrever la existencia de otros factores, ajenos a las prostaglandinas, en la hipermenorrea que se presenta en las usuarias de dispositivos intrauterinos no hormonales