title: Effect of the exposure to gentamicin and diltiazem on the permeability of model membranes.
abstract: Preliminary observations showed that the calcium-antagonist diltiazem enhances the 'in vitro' bactericidal action of the aminoglycoside gentamicin, especially against Gram-positive bacteria. To verify if a non-specific interaction of these two drugs with biomembranes may play a role in their synergic effect on bacterial cells, we have studied the effect of exposure to gentamicin, in the absence or presence of diltiazem, on the release of carboxyfluorescein (CF) trapped in phosphatidylcholine (PC) unilamellar vesicles (LUVs) used as model membranes. A significant leakage of trapped CF from PC LUVs was registered when liposomes were treated with gentamicin and diltiazem together, employed at doses (50 and 100 microg/ml, respectively) unable to affect CF release if applied alone; the combined effect of gentamicin and diltiazem was synergic and not cumulative. The present findings demonstrate that the simultaneous exposure to gentamicin and diltiazem may induce significant alterations in the permeability of phospholipid membranes and, so, very likely, in functional properties of bacterial membranes, targets of their action.
authors.affiliation: Department of Farmaco-Biologico, School of Pharmacy, University of Messina, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Trombetta
authors.forename: S
authors.initials: S
authors.lastname: Arena
authors.forename: A
authors.initials: A
authors.lastname: Tomaino
authors.forename: B
authors.initials: B
authors.lastname: Tita
authors.forename: G
authors.initials: G
authors.lastname: Bisignano
authors.forename: A
authors.initials: A
authors.lastname: De Pasquale
authors.forename: A
authors.initials: A
authors.lastname: Saija
mesh_terms: D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002121:Calcium Channel Blockers / Q000737:chemistry*; D004110:Diltiazem / Q000737:chemistry*; D005452:Fluoresceins; D005839:Gentamicins / Q000737:chemistry*; D008081:Liposomes; D008567:Membranes, Artificial; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D002121:Calcium Channel Blockers; D005452:Fluoresceins; D005839:Gentamicins; D008081:Liposomes; D008567:Membranes, Artificial; D010713:Phosphatidylcholines; C024098:6-carboxyfluorescein; D004110:Diltiazem