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.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Qiu R,Horvath A,Stahlmann Rdoi
10.1007/s00204-016-1743-6subject
Has Abstractpub_date
2016-08-01 00:00:00pages
1975-81issue
8eissn
0340-5761issn
1432-0738pii
10.1007/s00204-016-1743-6journal_volume
90pub_type
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