title: Evaluation of maduramicin and alborixin in a SCID mouse model of chronic cryptosporidiosis.
abstract: Two polyether ionophores, maduramicin and alborixin, were evaluated for anticryptosporidial activity in a severe combined immune deficient (SCID) mouse model of cryptosporidiosis. Groups of SCID mice were inoculated with 10(6) oocysts of bovine origin by oral gavage. Maduramicin or alborixin was administered beginning 4 weeks postinfection at 3 mg/kg of body weight per day. Maduramicin treatment resulted in a 96% reduction in fecal parasite load over the 3-week treatment period (P < 0.003). This reduction correlated with decreases in tissue parasite loads observed in histological sections of the small intestine (P < 0.000002) and the colon (P < 0.000006). A significant decrease in oocyst shedding was also observed after a 3-week treatment with alborixin (71% reduction, P < 0.01). Maduramicin was also evaluated in a relapsing model of cryptosporidiosis in which the infection was observed to recur after treatments were discontinued. Some toxicity, as demonstrated by weight loss, was observed with both maduramicin and alborixin. Both drugs exhibited significant anticryptosporidial activities with concomitant moderate toxicity. These polyether ionophores should be valuable as positive controls in compound evaluation studies and as lead compounds for chemical optimization (modification).
authors.affiliation: Department of Pediatrics, Emory University, Atlanta, Georgia 30022, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Mead
authors.forename: X
authors.initials: X
authors.lastname: You
authors.forename: J E
authors.initials: JE
authors.lastname: Pharr
authors.forename: Y
authors.initials: Y
authors.lastname: Belenkaya
authors.forename: M J
authors.initials: MJ
authors.lastname: Arrowood
authors.forename: M T
authors.initials: MT
authors.lastname: Fallon
authors.forename: R F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002908:Chronic Disease; D003457:Cryptosporidiosis / Q000188:drug therapy*; D005260:Female; D007783:Lactones / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D016513:Mice, SCID; D011714:Pyrans / Q000627:therapeutic use / Q000633:toxicity; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D007783:Lactones; D011714:Pyrans; C012708:alborixin; C018091:maduramicin