title: The differential antibacterial and gastrointestinal effects of erythromycin and its chiral isolates.
abstract: The use of erythromycin has been limited by the gastrointestinal side effect properties, which include abdominal distress and diarrhea. To evaluate the possibility of reducing the toxicity of erythromycin, studies were undertaken to separate erythromycin into chiral isolates and then to test the activity of these chiral isolates on gastrointestinal contractility and bacteriostatic actions. Gastrointestinal contractility was obtained by the use of isolated strips of a rat colon. Antibacterial activity was used by obtaining the MICs of erythromycin and isolated agents against Enterococcus faecalis ATCC 29212. ANOVA was performed using the SPSS v.10 to determine statistical differences in the MICs and the amplitude and frequency of spike bursts. Results were expressed as mean+/-SE (N=5). The MICs (microg/mL) of erythromycin (racemate), chiral isolate X, and chiral isolate Y were 0.45+/-0.29, 0.53+/-0.24 (n.s.), and 0.2+/-0.07 (P<or=0.001), respectively. Erythromycin (racemate) at 10 mol/L, 10 mol/L, 5x10 mol/L, 10 mol/L, and 10 mol/L concentrations caused the amplitude of spike bursts to increase by 18+/-7% (P=n.s.), 43+/-10% (P<or=0.05), 55+/-12% (P<or=0.001), 121+/-23% (P<or=0.001), and 163+/-16% (P<or=0.001), respectively. The chiral isolate Y increased the amplitude of spike bursts at the same concentrations as tested above: 32+/-11% (P<or=0.05), 48+/-14% (P<or=0.001), 84+/-13% (P<or=0.001), 112+/-18% (P<or=0.001), and 121+/-13% (P<or=0.001), respectively. Chiral isolate X caused much reduced effect on the amplitude of spike bursts: 9+/-6% (P=n.s.), 27+/-12% (P=n.s.), 27+/-12% (P=n.s.), 30+/-11% (P=n.s.), and 30+/-11.2% (P=n.s.), respectively. EC50 for erythromycin (mixture) was 0.4x10 mol/L, and for erythromycin Y, it was 0.8x10 mol/L. The addition of erythromycin at 10 mol/L caused the frequency of spike bursts to increase 11+/-7% at 10 mol/L, 5x10 mol/L, 10 mol/L, and 10 mol/L; the changes were 13+/-10% (P=n.s.), 13+/-10% (P=n.s.), 22+/-13% (P=ns), and 39+/-30% (P<or=0.05), respectively. Chiral isolate Y of erythromycin, changed the frequency of spike bursts by 26+/-21% (P=n.s.); 35+/-20% (P=n.s.), 39+/-30% (P=n.s.), 41+/-37% (P=n.s.), and 44+/-36% (P=n.s.) at the respective concentrations as discussed above. Chiral isolate X altered the frequency of spike bursts at the same concentrations as 40+/-30% (P=n.s.), 45+/-30% (P=n.s.), 62+/-41% (P=n.s.), 62+/-41% (P=n.s.), and 52+/-35% (P=n.s.), respectively. Data indicate that erythromycin (racemate) and chiral isolates X and Y possess similar antibacterial activity. It was also shown that erythromycin and chiral isolate Y increase significantly the amplitude of spike bursts compared with baseline. Isolate X does not increase the amplitude of spike bursts in a dose-dependent manner. The frequency of spike bursts is not significantly changed in the presence of erythromycin or the 2 chiral isolates.
authors.affiliation: Department of Pharmacology, Rush University, Chicago, Illinois, USA.
authors.forename: Ivana
authors.initials: I
authors.lastname: Cvetanovic
authors.forename: Vasant
authors.initials: V
authors.lastname: Ranade
authors.forename: Congrong
authors.initials: C
authors.lastname: Lin
authors.forename: John
authors.initials: J
authors.lastname: Somberg
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects / Q000502:physiology; D013293:Enterococcus faecalis / Q000187:drug effects; D004917:Erythromycin / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008826:Microbial Sensitivity Tests; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin