INHIBITION OF RAT PAROTID-GLAND GROWTH-RESPONSE INDUCED BY CHRONIC ISOPROTERENOL FOLLOWING TREATMENT WITH QUINOLONE ANTIBIOTICS

While antibiotics are broadly used in dental and medical therapy, litt le attention has been directed towards the potential toxic side effect s of antibiotics on tissue regeneration. Here we examined the effect o f a quinolone antibiotic, pefloxacin (Rhone Poulenc) on rat parotid gl and responses to chronic isoproterenol treatment. Groups of rats recei ved injections of isoproterenol to induce glandular growth, saline (co ntrols), pefloxacin, or isoproterenol and pefloxacin in combination. P arotid gland weight decreased significantly after pefloxacin treatment for 7 days as well as inhibiting glandular enlargement provoked by is oproterenol. The same trend was observed for the rates of DNA synthesi s, with the incorporation of [H-3]-thymidine in isoproterenol/pefloxac in-treated rats reduced to 49% of isoproterenol treatment alone levels . Saline-treated animals were 42% of the rate of [H-3]-thymidine incor poration into DNA observed in isoproterenol treated rats. While isopro terenol treatment increased steady-state mRNA levels for fos,jun, myc, src, c-erbB-2, ras and topo II, inclusion of pefloxacin with the isop roterenol regimen blocked these increases. Pefloxacin treatment by its elf did not alter proto-oncogene mRNA levels in the parotid gland. Gla ndular amylase activity was decreased in the pefloxacin treated group, while the combination of isoproterenol with pefloxacin did not decrea se glandular amylase levels to the extent of that observed with P-agon ist treatment alone. In acute experiments, pefloxacin significantly de creased the volume of saliva secreted by the parotid gland. These resu lts suggest that quinolone-based antibiotics disturb the secretory fun ction of the parotid gland and can inhibit cell proliferation and rege neration.