title: Effects of four nucleoside analogues used as antiviral agents on rat Sertoli cells (SerW3) in vitro.
abstract: Some nucleoside analogues are used to treat herpes simplex and other viral infections. They are known to impair spermatogenesis, but published data are scarce. We studied the effects of four nucleosides on SerW3 cells, a rat Sertoli cell line. Cells were cultured for 3 days in DMEM supplemented with four different concentrations of each drug. Aciclovir and ganciclovir were added at concentrations of 0.3, 1, 3 and 10 mg/l medium; penciclovir and its prodrug famciclovir were used at higher concentrations (3, 10, 30, 100 mg/l medium). After a culture period of 3 days, we analysed the expression of connexin43, N-cadherin and the cytoskeleton protein vimentin by Western blot. Aciclovir caused a clear-cut effect at the highest concentration tested (10 mg/l), which is less than the peak plasma concentration achieved in patients during intravenous therapy with the drug. Connexin43, vimentin and N-cadherin content decreased to 49.8 ± 17, 44.0 ± 4 and 75.4 ± 1.5 % of the control values, respectively (n = 3; mean ± SD). Similar effects were observed with the prodrug ganciclovir (43.2 ± 10.8; 54.1 ± 11.9; 84.4 ± 10.8 % of controls). Penciclovir caused less pronounced effects at 10 mg/l medium (82.1 ± 20.6; 90.0 ± 12.0; 76.5 ± 17.7 % of controls). Only a slight effect was observed with famciclovir. Even at a 10-fold concentration (100 mg/l), just moderate changes were induced. In summary, we observed clear-cut effects with aciclovir and ganciclovir on Sertoli cells in vitro at therapeutically relevant concentrations and identified connexin43 as the most sensitive marker.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Garystr. 5, 14195, Berlin, Germany.
authors.forename: Runan
authors.initials: R
authors.lastname: Qiu
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Garystr. 5, 14195, Berlin, Germany.
authors.forename: Aniko
authors.initials: A
authors.lastname: Horvath
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Garystr. 5, 14195, Berlin, Germany. ralf.stahlmann@charite.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Stahlmann
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000633:toxicity; D000212:Acyclovir / Q000031:analogs & derivatives / Q000633:toxicity*; D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics; D018929:Cell Culture Techniques; D002460:Cell Line; D018031:Connexin 43 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D000077595:Famciclovir; D015774:Ganciclovir / Q000633:toxicity; D006147:Guanine; D008297:Male; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism; D014746:Vimentin / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D015820:Cadherins; D018031:Connexin 43; C570099:N-cadherin, rat; D009419:Nerve Tissue Proteins; D014746:Vimentin; C053539:penciclovir; D015075:2-Aminopurine; D006147:Guanine; D015774:Ganciclovir; D000077595:Famciclovir; D000212:Acyclovir
keywords: Aciclovir; Famciclovir; Ganciclovir; Penciclovir; SerW3; Sertoli cells