Archives of Medical Research 31 (2000) S119–S121 0188-4409/00 $–see front matter. Copyright © 2000 IMSS. Published by Elsevier Science Inc. PII S0188-4409(00)00123-5 Effect of the Prostaglandin Analogue Misoprostol on Resistance to Entamoeba histolytica Infection in Balb/c Mice Blanca E. Sánchez-Ramírez,* Ernesto Ramos-Martínez,** Rocío Gaytán-Ochoa* and Patricia Talamás-Rohana*** *Facultad de Ciencias Químicas, **Departamento de Anatomía Patológica del Hospital Central Universitario, Facultad de Medicina, Universidad Autónoma de Chihuahua (UACH), Chihuahua, Mexico ***Departamento de Patología Experimental, Centro de Investigación y de Estudios Avanzados del I.P.N. (Cinvestav), Mexico City, Mexico Key Words: Entamoeba histolytica, Misoprostol, Prostaglandin, Mice. Introduction Amebic liver abscess (ALA) produced by Entamoeba his- tolytica infection is a common complication of invasive in- testinal amebiasis. Several experimental models, mainly ro- dents, have been used to study this parasitic infection, finding a great variability in susceptibility. Hamsters and gerbils are susceptible to hepatic amebiasis, while mice have been difficult to infect either intracecally or intrahepat- ically (1). Infections have been successfully induced using congenitally athymic nude (nu/nu) mice pretreated with sil- ica, which demonstrates that host resistance in murine ame- biasis is critically dependent upon the macrophage (1). Re- cent studies have demonstrated that inflammation mediators such as arachidonic acid (AA) metabolites, particularly prostaglandin E2 (PGE 2 ), can modulate T helper (TH) cells and participate in regulation of cooperator and effector mac- rophage functions (2). Previously, we demonstrated that during development of ALA in hamsters an increase in PGE 2 plasmatic levels occurs; furthermore, cyclooxygenase (COX) activity in liver tissue was augmented. In vivo in- domethacin (INDO) treatment, previous to the infection, had a beneficial effect on the host by limiting abscess devel- opment (3). To study the effect of PGs on natural resistance of Balb/c mice to E. histolytica infection, we tested exoge- nous PGs administration using the PGs analogue, misopros- tol (MPL). Materials and Methods Treatment and infection procedure. Male in-bred hamsters (Mesocricetus auratus), weighing approximately 100 g, were used as susceptible controls. Balb/c mice weighing ap- proximately 30 g were divided into groups with and without MPL treatment. Hamsters and mice were infected intrahe- patically with 7.5  10 5 trophozoites as described previ- ously (4). MPL (1  10 -4 M) dissolved in sterile water was injected intraperitoneally (i.p.) daily 1 h prior to the infec- tion procedure. For the group of infected and MPL-treated animals, drinking water was added with 0.25 g/mL of MPL. At days 2, 4, and 7 postinfection, animals were anes- thetized and killed by exsanguination. Livers and abscesses were removed to calculate the percentage of liver damage. Histology and immunohistochemistry. Specimens for his- tology were obtained from each group and fixed with 10% phosphate-buffered formalin. After embedding in paraffin, 6–8 m-thick sections were stained with hematoxylin and eosin (H&E). Liver sections were evaluated for the presence of trophozoites following the protocol enclosed with the Histostain-Plus Kit (Zymed Lab., Inc.), using a polyclonal antiameba antiserum (1:1000 dilution in blocking buffer). Results Intrahepatic inoculation of E. histolytica trophozoites in hamsters induced abscess formation in 100% of the animals. Lesions had typical macroscopic and microscopic aspects (4). Livers from infected hamsters at 2, 4, and 7 days postin- fection showed by immunohistochemistry the presence of trophozoites mainly at the periphery of necrosis. Livers from mice infected without MPL treatment Address reprint requests to: Dra. Blanca E. Sánchez-Ramírez, Facultad de Ciencias Químicas, UACH, Apdo. Postal 1542-C, 31000 Chihuahua, Chihuahua, México. Tel.: (+52) (14) 144-492; FAX: (+52) (14) 144-492; E-mail: bsanche@buzon.uach.mx Presenting author: Blanca E. Sánchez-Ramírez.