title: Inhibition of rat parotid gland growth response induced by chronic isoproterenol following treatment with quinolone antibiotics.
abstract: While antibiotics are broadly used in dental and medical therapy, little attention has been directed towards the potential toxic side effects of antibiotics on tissue regeneration. Here we examined the effect of a quinolone antibiotic, pefloxacin (Rhone Poulenc) on rat parotid gland responses to chronic isoproterenol treatment. Groups of rats received injections of isoproterenol to induce glandular growth, saline (controls), pefloxacin, or isoproterenol and pefloxacin in combination. Parotid gland weight decreased significantly after pefloxacin treatment for 7 days as well as inhibiting glandular enlargement provoked by isoproterenol. The same trend was observed for the rates of DNA synthesis, with the incorporation of [3H]-thymidine in isoproterenol/pefloxacin-treated rats reduced to 49% of isoproterenol treatment alone levels. Saline-treated animals were 42% of the rate of [3H]-thymidine incorporation into DNA observed in isoproterenol treated rats. While isoproterenol treatment increased steady-state mRNA levels for fos, jun, myc, src, c-erbB-2, ras and topo II, inclusion of pefloxacin with the isoproterenol regimen blocked these increases. Pefloxacin treatment by itself did not alter proto-oncogene mRNA levels in the parotid gland. Glandular amylase activity was decreased in the pefloxacin treated group, while the combination of isoproterenol with pefloxacin did not decrease glandular amylase levels to the extent of that observed with beta-agonist treatment alone. In acute experiments, pefloxacin significantly decreased the volume of saliva secreted by the parotid gland. These results suggest that quinolone-based antibiotics disturb the secretory function of the parotid gland and can inhibit cell proliferation and regeneration.
authors.affiliation: Clinic of Stomatology, University of Debrecen, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Kelentey
authors.forename: M
authors.initials: M
authors.lastname: Kerr
authors.forename: Z
authors.initials: Z
authors.lastname: Tao
authors.forename: K R
authors.initials: KR
authors.lastname: Purushotham
authors.forename: M G
authors.initials: MG
authors.lastname: Humphreys-Beher
authors.forename: T
authors.initials: T
authors.lastname: Zelles
mesh_terms: D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000494:pharmacology*; D000681:Amylases / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects* / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000235:genetics; D004347:Drug Interactions; D004587:Electrophoresis, Agar Gel; D005700:Galactosyltransferases / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007545:Isoproterenol / Q000009:adverse effects / Q000494:pharmacology*; D016759:Oncogene Protein p65(gag-jun) / Q000032:analysis / Q000235:genetics; D015688:Oncogene Protein pp60(v-src) / Q000032:analysis / Q000235:genetics; D016761:Oncogene Proteins v-fos / Q000032:analysis / Q000235:genetics; D010306:Parotid Gland / Q000187:drug effects* / Q000254:growth & development*; D015366:Pefloxacin / Q000009:adverse effects* / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics; D012463:Saliva / Q000187:drug effects / Q000378:metabolism; D018631:ras Proteins / Q000032:analysis / Q000235:genetics
chemical_list: D000318:Adrenergic beta-Agonists; D000681:Amylases; D000890:Anti-Infective Agents; D000242:Cyclic AMP; D004247:DNA; D017931:DNA Primers; D004250:DNA Topoisomerases, Type II; D005700:Galactosyltransferases; D007545:Isoproterenol; D016759:Oncogene Protein p65(gag-jun); D015688:Oncogene Protein pp60(v-src); D016761:Oncogene Proteins v-fos; D015366:Pefloxacin; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins